bluuebunny/crossref_metadata_2025 huggingface dataset:
The selenoprotein thioredoxin reductase is expressed in peripheral blood monocytes and THP1 human myeloid leukemia cells ‐ regulation by 1,25‐dihydroxyvitamin D3and selenite
Authors: Schütze Norbert , Fritsche Jana , Ebert‐Dümig Regina , Schneider Doris , Köhrle Josef , Andreesen Reinhard , Kreutz Marina , Jakob Franz
Published: December 2008

1,25(OH)2Vitamin D3(1,25(OH)2D3) and adhesion propagate monocyte differentiation. We identified the selenoprotein thioredoxin reductase (TrxR) as a new molecular target for 1,25(OH)2D3in monocytes during this process. In THP1 monocytic leukemia cells 1,25(OH)2D3stimulated TrxR mRNA levels 2—4‐fold by 4—8 h and enhanced TrxR activity (60%) (as measured by the dithionitrobenzole‐assay) after 24 h, which declined below baseline after 96 h. The addition of 100 nM selenite enhanced (approx. 50%) basal and stimulated enzyme activity in THP1 cells. The relative stimulation by 1,25(OH)2D3was very similar but peak levels were sustained in THP1 cells up to 48 h. Human peripheral blood monocytes (PBM) of different donors showed very low basal TrxR steady state mRNA levels which were markedly enhanced (as analyzed by Northern blotting) after 4 h of adherence to culture dishes. 1,25(OH)2D3(100 nM) further stimulated TrxR mRNA expression (4 h, 3‐fold). TrxR enzyme activity mirrored the mRNA changes. Basal activity was stimulated approx. 25% by adhesion in culture alone and was further stimulated (∼15%) by 1,25(OH)2D3after 4 h. By 24 h similar results were achieved but the effect of 1,25(OH)2D3could be seen in the presence of 100 nM selenium only. The expression of TrxR and its regulation by 1,25(OH)2D3and selenite in monocytes might be important for their induction of differentiation and maintenance of function.
Inhibition of cysteine protease and growth of Staphylococcus aureus V8 and poliovirus by phosphorylated cystatin α conjugate of skin
Authors: Takahashi Masae , Tezuka Tadashi , Korant Bruce , Katunuma Nobuhiko
Published: December 2008

The inhibitory properties of phosphorylated cystatin α (P‐cystatin α) and a conjugated protein of the P‐cystatin α with filaggrin linker segment peptide (FLSP) against the growth of Staphylococcus bacteria and poliovirus were investigated. Both the P‐cystatin α and the conjugated protein (P‐cystatin α‐FLSP conjugate) as a model for the cornified envelope of skin inhibited the cysteine protease activity of Staphylococcus aureus V8. The protease activity was inhibited by normal cornified envelope of newborn rat skin, which contains P‐cystatin α, and P‐cystatin α in cornified envelope of newborn rat skin also suppressed the growth of S. aureus V8. When P‐cystatin α or P‐cystatin α‐FLSP conjugate was added to cultured HeLa cells infected with poliovirus, 50—70% of the cell‐death due to poliovirus infection was prevented. The poliovirus 3C protease activity in the infected HeLa cells was inhibited by P‐cystatin α or P‐cystatin α‐FLSP conjugate. As a result, the processing of viral capsid peptides was suppressed. These findings suggest that P‐cystatin α and P‐cystatin α‐FLSP conjugate could play the role of the barrier against microorganism infections due to inhibition of their cysteine protease activities.
Cardiovascular effects of dietary copper deficiency
Authors: Saari Jack T. , Schuschke Dale A.
Published: December 2008

Dietary copper deficiency may impair cardiovascular health by contributing to high blood pressure, enhancement of inflammation, anemia, reduced blood clotting and arteriosclerosis. The purpose of this review is to compile information on the numerous changes of the heart, blood and blood vessels that may contribute to these cardiovascular defects. These alterations include weakened structural integrity of the heart and blood vessels, impairment of the use of energy by the heart, reduced ability of the heart to contract, altered ability of blood vessels to control their diameter and to grow, and altered structure and function of circulating blood cells. The fundamental causes of these changes rest largely on reduced effectiveness of enzymes that depend on copper for their activity.
The influence of the cytokines Il‐1β and INFγ on the expression of selenoproteins in the human hepatocarcinoma cell line HepG2
Authors: Hesse‐Bähr K. , Dreher I. , Körle J.
Published: December 2008

Metabolic labeling of HepG2 cells with 75selenite indicated the expression of more than four selenoproteins in the 80 to 45 kDa range and more than four selenoproteins in the 24 to 14 kDa range. Although there were no significant changes in the total protein content, determined by the method of BioRad, the densitometric analysis of the autoradiogramms showed a reduced expression of all labeled selenoproteins in the cell lysates of HepG2 after cytokine treatment for 24 hours. A stronger reduction was observed after treatment with ii‐1β than with IFNγ. Moreover, the inhibitory effects were more significant for those selenoproteins in the higher molecular mass range. Our data on the inhibition of selenoprotein synthesis and on repression of SeP promoter activity show that the expression of selenoproteins, especially of SeP, is influenced by acute phase reaction and pro‐inflammatory reactions.
Activation of the coenzyme at the early step of the catalytic cycle of tryptophanase
Authors: Ikushiro Hiroko , Kagamiyama Hiroyuki
Published: December 2008

Tryptophanase is catalytically more competent in alkaline pH even though the coenzyme exists as an inactive aldamine structure in this pH region. The binding of a substrate analog, 3‐indolepropionate to the enzyme shifts the equilibrium from the substituted aldamine to the ketoenamine form in the entire pH region studied. The resultant ketoenamine form is favorable for transaldimination with the substrate amino group, a prerequisite for subsequent catalysis. This implies that the binding of tryptophan in alkaline pH, where the enzyme shows maximum activity, converts the inactive aldamine form of the coenzyme to the active ketoenamine form, which is favorable for undergoing the next step of the catalytic process.
Phytate prevents tissue calcifications in female rats
Authors: Grases F. , Prieto R. M. , Simonet B. M. , March J. G.
Published: December 2008

The AIN‐76 A, a purified rodent diet, has a propensity to cause kidney calcifications in female rats which is not observed with non‐purified rodent diets, suggesting a nutritional factor that avoids these calcifications. One candidate is phytate, which inhibits crystallisation of calcium salts and is practically absent in purified diets. Therefore, the effects on calcification of kidney tissue of phytate addition to the AIN‐76 A diet using female Wistar rats were studied. The rats were assigned to three groups: AIN‐76 A, AIN‐76 A + 1% phytate and standard nonpurified chow. Urinary phytate of the AIN‐76 A fed group was undetectable. Urinary phytate of AIN‐76 A + 1% phytate and standard fed groups did not differ and was significantly higher than in the AIN‐76 A group. The concentrations of calcium and phosporus in kidneys were greater in the AIN‐76 A group than in AIN‐76 A + 1% phytate and standard groups. Only rats of the AIN‐76 A group displayed mineral deposits at the corticomedullary junction. These findings demonstrated that the absence of phytate in the AIN‐76 A diet is one of the causes of renal calcification in female rats.
Scavenger receptor regulation and atherosclerosis
Authors: Zingg Jean‐Marc , Ricciarelli Roberta , Azzi Angelo
Published: December 2008

Atherosclerosis and its complications, such as coronary heart disease, heart infarction and stroke, are the leading causes of death in the developed world. High blood pressure, diabetes, smoking and a diet high in cholesterol and lipids clearly increase the likelihood of premature atherosclerosis, albeit other factors, such as the individual genetic makeup, may play an additional role. During atherosclerosis, uncontrolled cholesterol and lipid accumulation in macrophages and smooth muscle cells leads to foam cell formation and to the progression of the atherosclerotic plaque. This review will focus on foam cell formation within the atherosclerotic lesion, the involvement of the scavenger receptor genes in this process, and the possibility to interfere with scavenger receptor function to reduce the progression of atherosclerosis. To date, the regulatory mechanisms for the expression of scavenger receptor genes and their role in atherosclerosis are not well characterized. Knowledge on this subject could lead to a better understanding of the process, prevention and therapy of this disease.
Alpha‐tocopherol protects against monocyte Mac‐1 (CD11b/CD18) expression and Mac‐1‐dependent adhesion to endothelial cells induced by oxidized low‐density lipoprotein
Authors: Terasawa Yoshimitsu , Manabe Hiroki , Yoshida Norimasa , Uemura Manabu , Sugimoto Naohito , Naito Yuji , Yoshikawa Toshikazu , Kondo Motoharu
Published: December 2008

α‐Tocopherol supplementation is reported to protect against cardiovascular disease and to influence cells involved in atherogenesis, such as monocytes. Interactions between monocytes and vascular endothelial cells occur early in atherogenesis, and adhesion is mediated by integrins. We evaluated the effects of α‐tocopherol on expression of Mac‐1 (CD11b/CD18) by monocytes after stimulation with oxidized low‐density lipoprotein (LDL), which is implicated as a potent chemotactic agent in atherogenesis. Incubation of whole blood with oxidized LDL (100 ± 119 g/ml) increased Mac‐1 expression on monocytes, and preincubation with α‐tocopherol reduced this upregulation in a concentration dependent manner. In another experiment, whole blood was obtained from healthy adult volunteers after 10 days of α‐tocopherol administration (600 mg/day) and was incubated with oxidized LDL (100 μg/ml). There was a decrease in the upregulation of Mac‐1 compared with that measured before administration. Adherence of oxidized LDL‐stimulated monocytes to human umbilical vein endothelial cells was reduced by pretreatment with α‐tocopherol, and was also inhibited by an anti‐CD18 monoclonal antibody. Experiments with protein kinase C inhibitors suggested that reduction of Mac‐1 upregulation by α‐tocopherol was secondary to a decrease of protein kinase C activity. In conclusion, α‐tocopherol suppressed the upregulation of Mac‐1 expression on monocytes by oxidized LDL.
Effects of food factors on signal transduction pathways
Authors: Dong Zigang
Published: December 2008

Consumption of plant‐derived foods, especially fruits and vegetables, has been linked to decreased risk of cancer. Laboratory studies with animals and cells in culture have shown cancer preventive activity of chemicals isolated from soy, tea, rice and many green, yellow and orange fruits and vegetables. Using cell culture, transgenic mice and knockout mice models to examine the anti‐cancer effects of these dietary factors at the molecular level, we found that (1) (‐)‐epigallocatechin gallate (EGCG), the major active polyphenol in green tea, and theaflavins, the major active components in black tea, inhibit epidermal growth factor (EGF)‐ or 12‐O‐tetradecanoylphorbol‐13‐acetate (TPA)‐induced JB6 cell transformation. At the same dose range that inhibited cell transformation, EGCG and theaflavins inhibited activator protein‐1 (AP‐1) activation. These compounds also inhibited ultraviolet B (UVB)‐induced AP‐1 and nuclear factor kappa B (NFκB)‐dependent transcriptional activation; (2) resveratrol, found at high levels in grapes, inhibited cell transformation through the induction of apoptosis, mediated through JNK and p53‐dependent pathways; (3) inositol hexaphosphate (InsP6), an active compound from rice and other grains, inhibited TPA‐ or EGF‐induced transformation and signal transduction through its effects on phosphatidylinositol‐3 kinase (PI‐3) kinase; (4) phenethyl isothiocyanate (PEITC), which occurs as a conjugate in certain cruciferous vegetables, inhibited cell transformation corresponding with the induction of apoptosis. An elevation of p53 is required for PEITC‐induced apoptosis. Our studies indicated that the chemopreventive effect of these food factors may be mediated by their effects on different signal transduction pathways; (5) retinoids (vitamin A and its metabolites) inhibited tumor promoter‐induced cell transformation and tumor promotion in transgenic mice through the inhibition of AP‐1 action but not through the activation of retinoic acid response element (RARE).
Zinc deficiency and taste dysfunction; Contribution of carbonic anhydrase, a zinc‐metalloenzyme, to normal taste sensation
Authors: Komai Michio , Goto Tomoko , Suzuki Hitoshi , Takeda Tomohiko , Furukawa Yuji
Published: December 2008

The present study was designed to clarify the effect of zinc deficiency on sodium chloride preference, the lingual trigeminal and taste nerves transduction, and carbonic anhydrase (CA) activity of the tongue surface and salivary gland. Male SD rats, 4 weeks old, were divided into four groups, and fed zinc‐deficient (Zn‐Def), low‐zinc (Low‐Zn), and zinc‐sufficient diets with free access (Zn‐Suf) and pair‐feeding (Pair‐fed). After taking part in the preference tests for 42 days, the rats were provided for the chorda tympani and lingual trigeminal nerves recordings, then finally sacrificed and the tongue and submandibular gland excised to measure CA activity.

Sodium chloride preference increased only after 4 days of the feeding of zinc‐deficient and low‐zinc diets, which means that the taste abnormality appears abruptly in zinc deficieny and even though in marginal zinc deficiency. Reduced CA activities of the taste‐related tissues in zinc‐deficient group paralleled well with the decreased taste and lingual trigeminal nerves sensitivities.
Prevention of colon carcinogenesis and carcinoma metastasis by orally administered bovine lactoferrin in animals
Authors: Tsuda Hiroyuki , Sekine Kazunori , Takasuka Nobuo , Toriyama‐Baba Hiroyasu , Iigo Masaaki
Published: December 2008

Bovine lactoferrin (bLF), a milk protein known to have bacteriostatic properties was examined for its preventive effects on colon and other organ carcinogenesis and experimental metastasis. (Experiment 1) The influence on colon carcinogenesis was investigated in male rats treated with azoxymethane (AOM), then received 2 or 0.2% weeks. Significant reduction in the incidence (27% control, respectively) and number of adenocarcinomas of the large intestine was observed. (Experiment 2) In BALB/c mice bearing subcutaneous (s.c.) implants of colon carcinoma 26 (Co 26Lu), bLF demonstrated significant inhibition of spontaneous lung metastasis (approximately 43% and CD8+ cells in white blood cells increased (171% control, respectively) after treatment. Results of those experiments indicate that bLF remarkably prevents colon carcinogenesis and lung metastasis of colon carcinoma cells, possibly due to increasing cytotoxic cells in the peripheral blood.
Dietary intake and cancer mortality in Japan
Authors: Matsumura Yasuhiro , Yoshiike Nobuo , Yokoyama Tetsuji , Tanaka Heizo
Published: December 2008

We examined the correlation between the prefectural variation of standardized mortality ratio (SMR) for lung and colon cancer and the consumption of foods using dietary data from National Nutrition Survey in Japan from 1976 to 1995. We found partly the same results on promoting factors and preventing factors of these cancers as the previously reported large scale cohort studies. But, we also found the inconsistent results. This might be partly because of the limitation of data collection method in the National Nutrition Survey. It was thought that the method of National Nutrition Survey should be modified to monitor nutrition and health conditions to correspond the epidemiological study and to prevent chronic diseases.
Inhibitory effects of curcumin and capsaicin on phorbol ester‐induced activation of eukaryotic transcription factors, NF‐κB and AP‐1
Authors: Surh Young‐Joon , Han Seong Su , Keum Young‐Sam , Seo Hyo‐Joung , Lee Sang Sup
Published: December 2008

Recently, considerable attention has been focused on identifying dietary and medicinal phytochemicals that can inhibit, retard or reverse the multi‐stage carcinogenesis. Spices and herbs contain phenolic substances with potent antioxidative and chemopreventive properties. Curcumin, a yellow colouring agent from turmeric and capsaicin, a pungent principle of red pepper exhibit profound anticarcinogenic and antimutagenic activities. Two well‐defined eukaryotic transcription factors, nuclear factor‐kappa B (NF‐κB) and activator protein 1 (AP‐1) have been implicated in pathogenesis of many human diseases including cancer. These transcription factors are known to be activated by a wide array of external stimuli, such as tumor promoter 12‐O‐tetradecanoylphorbol‐13‐acetate (TPA), tumor necrosis factor, reactive oxygen species, bacterial lipopolysaccharide, and ultraviolet. In the present study, we found that topical application of TPA onto dorsal skin of female ICR mice resulted in marked activation of epidermal NF‐κB and AP‐1. Curcumin and capsaicin, when topically applied prior to TPA, significantly attenuated TPA‐induced activation of each transcription factor in mouse skin. Likewise, both compounds inhibited NF‐κB and AP‐1 activation in cultured human promyelocytic leukemia (HL‐60) cells stimulated with TPA. Based on these findings, it is likely that curcumin and capsaicin exert anti‐tumor promotional effects through suppression of the tumor promoter‐induced activation of transcription factors, NF‐κB and AP‐1.
COX‐2 and iNOS, good targets for chemoprevention of colon cancer
Authors: Watanabe Kouji , Kawamori Toshihiko , Nakatsugi Seiichi , Wakabayashi Keiji
Published: December 2008

Cyclooxygenase (COX)‐2 has been suggested to play an important role in colon carcinogenesis. We found that the COX‐2 selective inhibitor, nimesulide, reduces azoxymethane (AOM)‐induced aberrant crypt foci (ACF) in rats and colon carcinogenesis in mice, as well as formation of intestinal polyps in Min mice. Thus, selective inhibitors of COX‐2, which catalyzes the synthesis of prostanoids, could be good candidates as chemopreventive agents against colon cancer. Examination of the effect of prostanoid receptor deficiency and a selective antagonist of prostanoid receptor on the development of AOM‐induced ACF in mice revealed the involvement of the EP_1 receptor. Moreover, a selective EP_1 antagonist reduced the number of intestinal polyps in Min mice. These results suggest that PGE_2 contributes to colon carcinogenesis through binding to the EP_1 receptor. Nitric oxide synthase (NOS) is known to be overexpressed in colon cancers of humans and rats, and a NOS inhibitor, L‐NG‐nitroarginine methyl ester, was found to inhibit the development of AOM‐induced ACF in rats. Thus, NOS including iNOS could also be a good target for chemoprevention of colon cancer, as in the COX‐2 case.
Effects of L‐lysine deficient diet on the hypothalamic interstitial norepinephrine and diet‐induced thermogenesis in rats in vivo
Authors: Smriga M. , Murakami H. , Mori M. , Torii K.
Published: December 2008

Rats readily recognize an amino acid deficient diet, presumably via central mechanisms that involve hypothalamic circuits. Presently, effects of the essential amino acid L‐lysine deficiency on the ventromedial (VMH) and lateral (LH) hypothalamus norepinephrine (NE) release were evaluated in free moving rats. Microdialysis measurement was undertaken once in 48 h (12:00 noon–14:00) in rats that had free access to food and drink. Significant decline in the food intake and VMH NE release were found in rats fed L‐lysine diet. No changes were identified in LH NE release. Additionally, no significant differences in diet‐induced spatial thermogenesis between normal and L‐lysine deficient non‐stressed rats were found in vivo. The results suggested that the VMH NE release was specifically involved in the integration of signals about amino acid deficiency. However, the decrease in VMH NE was not translated into changes of thermogenic responses to diet.
Antitumor protein (AP) from a mushroom induced apoptosis to transformed human keratinocyte by controlling the status of pRb, c‐MYC, cyclin E‐cdk2, and p21WAF1 in the G1/S transition
Authors: Kawamura Yukio , Manabe Mariko , Kitta Kazumi
Published: December 2008

Antitumor protein (AP) from a mushroom, induced the morphological changes typical to apoptosis such as nuclear condensation, aneuploidity, and DNA fragmentation at concentrations as low as 5–20 ng/ml to cancer cells. Molecular alterations related to cell cycle. Molecular alterations related to cell cycle, especially G1/S transition were investigated with a human keratinocyte transformed with oncoproteins, E6 and E7 of human pappiloma virus(HPV)‐16. AP didn't alter significantly and oncosuppressor p53 level, but induced hyperphosphorylation of pRb. Time‐dependent change of G1 cyclins, cdk2 and cdk4 after addition of AP showed that expression level of cdk inhibitors, INK4 family, and p27KIP1 did not altered, while that of p21WAF1 was downregulated.
Factors affecting flavonoids absorption
Authors: Piskula Mariusz K.
Published: December 2008

In experiments on rats, some of the factors affecting flavonoids absorption (solubility, glycosylation and nutritional status: fasted and not‐fasted animals) were examined. Administration of quercetin with different solubilization degree showed no direct correlation between the quercetin absorption extent and solubility, i.e. despite 3 orders of difference in solubilization degree, the extent of absorption varied only about 4‐fold. Absorption comparison of genistein and its glycoside genistin showed no difference in the extent of absorption; however, aglycone, in contrast to glycoside, was absorbed already from the rat stomach. Conjugation patterns (sulfation and glucuronization) of genistein metabolites demonstrated that the plasma of animals fasted prior to isoflavone administration contained significantly more sulfates and less glucuronides and mixed sulfates/glucuronides conjugates than the plasma of non‐fasted animals.
Suppressive effects of flavonoids on dioxin toxicity
Authors: Ashida Hitoshi
Published: December 2008

Dioxin type chemicals such as 2,3,7,8‐tetrachlorodibenzo‐p‐dioxin (TCDD) cause a variety of toxicity. Most of the toxicity of TCDD has been attributed to a mechanism by which TCDD is bound to aryl hydrocarbon receptor (AhR) and transforms the receptor. Thus, suppression of the AhR transformation by food factors can suppress the dioxin toxicity. In this study, flavonoids at various concentrations were treated to a rat cytosolic fraction containing AhR before adding 1 nM TCDD. The transformed AhR was detected by an electrophoretic mobility shift assay with a DNA oligonucleotide consensus to dioxin response element. As the results, flavones and flavonols at dietary levels act as the antagonists for AhR and suppress the transformation. The antagonistic IC50values were in a range between 0.14 and 10 μM, which are close to the physiological levels in human. These results suggest that a plant‐based diet can prevent the dioxin toxicity.
The effects of soy protein in women and men with elevated plasma lipids
Authors: Mackey R. , Ekangaki A. , Eden J. A.
Published: December 2008

Fifty four postmenopausal women with elevated cholesterol were recruited for a randomised, double‐blind controlled trial of soy protein containing isoflavones. (ISP+) or a soy protein with a low isoflavone content (ISP‐), taken daily for 12 weeks. There was an overall reduction after 12 weeks in total cholesterol (TC), LDL cholesterol (LDL‐C), sex hormone binding globulin (SHBG), and luteinizing hormone (LH). There were no significant differences between treatment groups. In a separate study 27 male subjects with a TC > 5.5 mmol/l were given ISP+ for 12 weeks. In this male study there was a significant increase in HDL cholesterol (HDL‐C) and SHBG. Soy protein has a cholesterol lowering effect in both women and men. These studies suggest that this effect is independent of isoflavones. Soy protein also reduces SHBG levels in both sexes.
Modulation of cell‐cell communication in the cause and chemoprevention/chemotherapy of cancer
Authors: Trosko James E. , Chang Chia Cheng
Published: December 2008

Chemopreventive or chemotherapeutic agents have been those that either kill cancer cells to a differential degree over the non‐cancer cells or those chemicals that either block the induction of tumors in carcinogen‐treated animals or retard transplanted tumors in animals. Carcinogenesis is a multi‐stage, multi‐mechanism process, involving the irreversible alteration of a stem cell (“initiation”), followed by the clonal proliferation of the initiated cell (“promotion”). To develop a strategy for intervention with chemoprevention/chemotherapeutic chemicals, the basic mechanism(s) of carcinogenesis must be understood. Gap junction intercellular communication (GJIC) regulates cell growth, differentiation, apoptosis and adaptive functions of differentiated cells. Normal cells have functional GJIC while cancer cells do not. Tumor promoters and oncogenes inhibit GJIC, while anti‐tumor promoter and anti‐oncogene drugs can reverse the down‐regulation of GJIC. Transfection of gap junction genes (connexins) has been shown to reverse the tumorigenic phenotype. If prevention/treatment of cancer is to occur, prevention of the chronic down regulation of GJIC by tumor promoters in non‐tumorigenic but initiated cells or the up‐regulation of GJIC in stably down‐regulated GJIC in tumor cells must occur to prevent or to treat cancers.
Effects of the administration of wheat bran biscuit: Changes in the diet
Authors: Ishikawa Hideki , Akedo Ikuko , Nakamura Tomiyo , Kimura Kazuko , Takimoto Yasuko , Suzuki Takaichiro , Sato Shinichi , Tanaka Yukio , Otani Toru
Published: December 2008

We developed hard biscuit containing 30% bran (WB biscuit) and administered it to 12 volunteers at 7.5 g/day (7.5 g group) or 15 g/day (15 g group) as wheat bran for 12 weeks.

After 12 weeks, the dietary fiber intake from foods other than wheat bran decreased slightly in the both groups, in the 15 g group was the decrease notable especially, after the beginning of WB biscuit administration.

We suggest that a closest attention to changes in dietary habit associated with intervention is needed in intervention studies using patients leading a normal life.
Metabolic effects of ω‐3 fatty acids
Authors: Osmundsen Harald , Clouet Pierre
Published: December 2008

Some metabolic effects of dietary marine oils, or of dietary eicosapentaenoic or docosahexaenoic acid are reviewed. It is pointed out that docosahexaenoic acid appears more effective as regards induction of peroxisomal β‐oxidation. Similarly, docosahexaenoic appears more powerful in terms of suppression of hepatic Δ9‐desaturase activity and mRNA‐levels. The potential inhibitory effect of polyunsaturated fatty acids, particularly docosahexaenoic acid, on mitochondrial β‐oxidation is discussed. Experiments with rats suggesting that the hypolipidaemic response of eicosapentaenoic acid is more marked when the fatty acid was given to fed rats, as compared to fasted rats, are discussed.
Role of dietary lipids in arteriosclerosis in experimental animals
Authors: Imaizumi Katsumi , Adan Yosef , Shibata Kenichi
Published: December 2008

Effects of dietary fats include the development of arteriosclerosis in humans and experimental animals, in addition to hypercholesterolemia. None of the preceding studies explicitly compared the effects of individual fatty acids. To address these issues, we chose exogenously hypercholesterolemic (ExHC) rats and apolipoprotein (apo) E deficient mice as a model for atherosclerosis and assessed the individual role of fatty acids in animals' susceptibility to atherosclerosis. The rats fed on the diet containing DHA or EPA, compared with those fed on the safflower oil (SO) diet, lowered serum cholesterol concentration, prevented platelet aggregation and slowed thickening in the ascending aorta. Apo E deficient mice developed hypercholesterolemia and severe lesion area in aortic root and arch, to a similar extent when they received DHA or SO. These results suggest a direct action of polyunsaturated fatty acids in the arterial wall, in addition to their effects on hypocholesterolemic and haemodynamic action.
Preventive effects of drinking green tea on cancer and cardiovascular disease: Epidemiological evidence for multiple targeting prevention
Authors: Nakachi Kei , Matsuyama Satoru , Miyake Satoshi , Suganuma Masami , Imai Kazue
Published: December 2008

The significance of drinking green tea in prevention of two of the main lifestyle‐related diseases, cancer and cardiovascular disease, was demonstrated in terms of a prospective cohort study on a total of 8,552 general residents in Saitama Prefecture, Japan. On the basis of the follow‐up study, we revealed decreased relative risk of cancer incidence for those consuming over 10 cups a day, compared with those consuming below 3 cups: 0.54 (95% men, 0.57 (0.34–0.98) for women, and 0.59 (0.35–0.98) for both sexes. Furthermore, a significant delay in cancer onset was associated with increased consumption of green tea. Next, decreased relative risk of death from cardiovascular disease was 0.58 (0.34–0.99) for men, 0.82 (0.49–1.38) for women, and 0.72 (0.60–1.04) for members of both sexes consuming over 10 cups a day. Finally, we evaluated the life‐prolonging effects of drinking green tea on cumulative survival, using the life table.
Regulation of intestinal glucose transport by tea catechins
Authors: Shimizu Makoto , Kobayashi Yoko , Suzuki Miho , Satsu Hideo , Miyamoto Yusei
Published: December 2008

Intestinal glucose uptake is mainly performed by its specific transporters, such as SGLT 1, GLUT 2 and 5 expressed in the intestinal epithelial cells. By using human intestinal epithelial Caco‐2 cells we observed that intestinal glucose uptake was markedly inhibited by tea extracts. While several substances in green tea seem to be involved in this inhibition, catechins play the major role and epicatechin gallate (ECg) showed the highest inhibitory activity. Since our Caco‐2 cells did not express enough amount of SGLT 1, the most abundant intestinal glucose transporter, the effect of ECg on SGLT 1 was evaluated by using brush border membrane vesicles obtained from the rabbit small intestine. ECg inhibited SGLT 1 in a competitive manner, although ECg itself was not transported via the glucose transporters. These results suggest that tea catechins could play a role in controlling the dietary glucose uptake at the intestinal tract and possibly contribute to blood glucose homeostasis.
Mechanisms of inhibition of carcinogenesis by tea
Authors: Yang Chung S. , Chung Jee Y. , Yang Guang‐Yu , Li Chuan , Meng Xiaofeng , Lee Mao‐Jung
Published: December 2008

Tea (Camellia sinensis) preparations have been shown to inhibit tumorigenesis at the initiation, promotion, and progression stages in different animal models. The anti‐proliferative effects of tea polyphenols may be a key mechanism, especially in the NNK‐induced lung tumorigenesis model with mice. Studies with cell lines have demonstrated that tea polyphenols inhibit cell proliferation and induce apoptosis. The effective concentrations used in these studies (20–100 μM) are usually higher than those observed in blood and tissues of humans and animals, which are in the low micromolar range. Glucuronide and sulfate conjugated and methylated catechins as well as ring fission products (due to intestinal microflora) have been observed in human plasma and urine. Purified green and black tea polyphenols inhibited the H‐ras induced mitogen‐activated protein kinases, AP‐1 activities, and the growth of 30.7b Ras 12 and BES21 cells. Among the catechins, both the galloyl structure on the B ring and the gallate moiety are important for the inhibition. Both (‐)‐epigallocatechin‐3‐gallate and theaflavin‐3,3′‐digallate inhibited the phosphorylation of c‐jun and p44/42 (ERK 1/2). More mechanistic and human studies in these areas will help us to understand the possible inhibitory action of tea against carcinogenesis in humans.
The role of anthocyanins as an antioxidant under oxidative stress in rats
Authors: Tsuda Takanori , Horio Fumihiko , Osawa Toshihiko
Published: December 2008

Cyanidin 3‐O‐β‐d‐glucoside (C3G) is included in anthocyanins, and expected to have a potency to scavenge active oxygen species in vivo. Rats were fed a diet containing C3G (2 g/kg diet) for 14 days, and then subjected to hepatic ischemia‐reperfusion (I/R) as an oxidative stress model. I/R treatment elevated the liver thiobarbituric acid‐reactive substance concentration and the serum activities of marker enzymes for liver injury, and lowered the liver reduced glutathione concentration. Feeding C3G significantly suppressed these changes caused by hepatic I/R. These results indicate that C3G functions as a potent antioxidant in vivo under oxidative stress. To clarify the mechanism of action of C3G, we investigated the absorption and metabolism of C3G in rats. C3G appeared in the plasma immediately after the oral administration of C3G. Protocatechuic acid, which seems to be produced by the degradation of cyanidin, was also present in the plasma. In the liver and kidneys, C3G was metabolized to methylated form.
Recent studies on the biofunctions and biotransformations of curcumin
Authors: Lin Jen‐Kun , Pan Min‐Hsiung , Lin‐Shiau Shoei‐Yn
Published: December 2008

Curcumin is a major component of Curcuma species, which is commonly used as a yellow coloring and flavoring agent in foods. Curcumin has shown anti‐carcinogenic activity in animals as indicated by its ability to block colon tumor initiation by azoxymethane and skin tumor promotion induced by phorbol ester TPA. Curcumin possesses anti‐inflammatory activity and is a potent inhibitor of reactive oxygen‐generating enzymes such as lipoxygenase/cyclooxygenase, xanthine dehydrogenase/oxidase and inducible nitric oxide synthase. Curcumin is also a potent inhibitor of protein kinase C, EGF‐receptor tyrosine kinase and IκB kinase. Subsequently, curcumin inhibits the activation of NFκB and the expressions of c‐jun, c‐fos, c‐myc and iNOS. It is proposed that curcumin may suppress tumor promotion through blocking signal transduction pathways in the target cells. Curcumin was first biotransformed to dihydrocurcumin and tetrahydrocurcumin and that these compounds subsequently were converted to monoglucuronide conjugates. These results suggest that curcumin‐glucuronide, dihydro‐curcumin‐glucuronide, tetrahydrocurcumin‐glucuronide and tetrahydrocurcumin are major metabolites of curcumin in mice.
Chemistry and antioxidative factors in rosemary and sage
Authors: Ho Chi‐Tang , Wang Mingfu , Wei Guor‐Jien , Huang Tzou‐Chi , Huang Mou‐Tuan
Published: December 2008

Rosemary and sage are common spices used in food. In our recent search of cancer chemopreventive agents from spices, the alcohol extracts of rosemary and sage showed strong antumorigenic activities. Rosemary and sage extracts contain active antioxidative factors such as phenolic diterpenes, flavonoids and phenolic acids. Here we discuss chromatographic methods used to separate and purify compounds from these spices and MS and NMR spectrometry to identify the isolated compounds. Several new compounds isolated from sage were determined to be 6‐O‐caffeoyl‐β‐D‐fructofuranosyl‐(2 → 1)‐β‐glucopyranoside, 1‐O‐caffeoyl‐β‐D‐apiofuranosyl‐(1 → 6)‐β‐D‐glucopyranoside, 1‐O‐p‐hydroxybenzoyl‐β‐D‐apiofuranosyl‐(1 → 6)‐β‐D‐glucopyranoside, 1‐O‐(3‐methyl‐2,3,4‐trihydroxybutyl)‐6‐O‐feruloyl‐β‐D‐glucopyranoside, 4‐hydroxyacetophenone 4‐O‐[5‐O‐(3,5‐dimethoxy‐4‐hydroxybenzoyl)‐β‐D‐apiofrunosyl]‐(1 → 2)‐β‐D‐glucopyranoside and 1‐O‐[2‐hydroxy‐5‐(2‐hydroxyethyl)phenyl]‐6‐O‐trans‐caffeoyl‐β‐D‐glucopyranoside.
Antidiabetogenic activity of oleanolic acid glycosides from medicinal foodstuffs
Authors: Yoshikawa Masayuki , Matsuda Hisashi
Published: December 2008

Oleanolic acid glycosides from several medicinal foodstuffs were found to show potent inhibitory activity on the increase of serum glucose levels in oral glucose‐loaded rats. By examination of the structure‐activity relationships, the 3‐O‐glucuronide moiety and the 28‐carboxyl group in oleanolic acid glycosides were required to exert the hypoglycemic activity. Oleanolic acid glycosides were found to have neither insulin‐like nor insulin‐releasing activity, but they inhibited gastric emptying and glucose‐uptake in the small intestine. Investigation of the mode of action revealed that the inhibition of gastric emptying was mediated by capsaicin‐sensitive sensory nerves and the central nervous system. Furthermore, oleanolic acid glycosides were suggested to suppress the gastric emptying by stimulating the release and/or production of dopamine to act through dopamine2 receptors, which in turn causes the release of prostaglandins.
Inhibitory effects of vitamin E on endothelial‐dependent adhesive interactions with leukocytes induced by oxidized low density lipoprotein
Authors: Yoshida N. , Manabe H. , Terasawa Y. , Nishimura H. , Enjo F. , Nishino H. , Yoshikawa T.
Published: December 2008

Leukocyte‐endothelial cell interactions, which are mediated by various adhesion molecules, are a crucial event in inflammatory reactions including atherosclerosis. α‐Tocopherol (α‐Toc) has been used for protection and therapy of vascular diseases because of its antioxidant activity. The objective of the present study was to determine effect of α‐Toc on endothelial‐dependent adhesive interactions with leukocytes elicited by oxidized low density lipoprotein (oxLDL). Incubation of HUVEC with oxLDL (100 μg/mL) increased expression of proteins and messenger RNA of intercellular adhesion molecule‐1 (ICAM‐1) and vascular cell adhesion molecule‐1 (VCAM‐1) on enzyme immunoassay and northern blotting assay; pretreatment with α‐Toc reduced in a dose dependent manner. Adherence of polymorphonuclear leukocytes (PMN) or mononuclear leukocytes (MNC) to oxLDL‐activated HUVEC was much increased compared with that to unstimulated HUVEC. Treatment of HUVEC with α‐Toc, monoclonal antibody to ICAM‐1 or VCAM‐1 inhibited adherence of PMN or MNC in a dose dependent manner. These results suggest that α‐Toc works as anti‐atherogenic agent through inhibiting endothelial‐dependent adhesive interactions with leukocytes induced by oxLDL.
Selenoprotein synthesis in archaea
Authors: Rother Michael , Resch Armin , Wilting Reinhard , Böck August
Published: December 2008

The availability of the genome sequences from several archaea has facilitated the identification of the encoded selenoproteins and also of most of the components of the machinery for selenocysteine biosynthesis and insertion. Until now, selenoproteins have been identified solely in species of the genera Methanococcus (M.) and Methanopyrus. Apart from selenophosphate synthetase, they include only enzymes with a function in energy metabolism. Like in bacteria and eukarya, selenocysteine insertion is directed by a UGA codon in the mRNA and involves the action of a specific tRNA and of selenophosphate as the selenium donor. Major differences to the bacterial system, however, are that no homolog for the bacterial selenocysteine synthase was found and, especially, that the SECIS element of the mRNA is positioned in the 3′ nontranslated region. The characterisation of a homolog for the bacterial SelB protein showed that it does not bind to the SECIS element necessitating the activity of at least a second protein. The use of the genetic system of M. maripaludis allowed the heterologous expression of a selenoprotein gene from M. jannaschii and will facilitate the elucidation of the mechanism of the selenocysteine insertion process in the future.
Selenium: A key element that controls NF‐κB activation and IκBα half life
Authors: Kretz‐Remy Carole , Arrigo André‐Patrick
Published: December 2008

Treatment of mammalian cells with hydrogen peroxide induces the nuclear translocation of the transcription factor NF‐κ and its binding to κ DNA sequences present in the promoter region of numerous genes. The role of selenium in NF‐κ activation was analyzed in human T47D cells overexpressing the seleno‐dependent detoxifiant enzyme glutathione peroxidase. Following exposure to H2O2, these cells showed a seleno‐dependent decreased accumulation of intracellular ROS and NF‐κ activation. This phenomenon was correlated with an inhibition of the nuclear translocation of NF‐κ (p50 subunit) and with an absence of Iκα degradation. We also report that the half‐life of Iκα in untreated cells was increased two‐fold by the overexpression of active glutathione peroxidase. These results suggest that selenium is a key element that through its modulation of glutathione peroxidase activity can inhibit NF‐κ activation and can up‐regulate Iκα normal half life.
Selenium and signal transduction: Roads to cell death and anti‐tumour activity
Authors: Ghose Aurnab , Fleming Janis , Harrison Paul R.
Published: December 2008

Accumulated evidence from prospective studies, intervention trials and studies on animal models of cancer have suggested a strong inverse correlation between selenium intake and cancer incidence. Several putative mechanisms have been suggested to mediate the chemopreventive activities of selenium: of these, the inhibition of cellular proliferation and the induction of apoptosis are particularly attractive.

The mitogen activated protein kinase (MAPK) pathways are known to be important regulators of cell death and our recent work has focused on the involvement of these pathways in selenium‐induced apoptosis in primary cultures of oral cancers and corresponding normal mucosa derived from biopsy material.

Using this system, the oral carcinoma cells were found to have enhanced sensitivity to apoptosis when treated with certain selenium compounds compared to normal oral mucosa. Induction of Fas ligand was associated with selenium‐induced apoptosis.

Signal transduction studies suggests that selenium induces several changes in the MAPK signalling pathways but functional intervention/inhibitor studies indicate that activation of the JNK pathway seems to be most important.
The Drosophilaselenophosphate synthetase (selD) gene is required for development and cell proliferation
Authors: Serras Florenci , Morey Marta , Alsina Berta , Baguñà Jaume , Corominas Montserrat
Published: December 2008

To study the function of selenoproteins in development and growth we have used a lethal mutation (selDptuf} of the Drosophila homologous selenophosphate synthetase (selD) gene. This enzyme is involved in the selenoprotein biosynthesis. The selDptuf loss‐of‐function mutation causes aberrant cell proliferation and differentiation patterns in the brain and imaginal discs, as deduced from genetic mosaics, patterns of gene expression and analysis of cell cycle markers. In addition to that, selenium metabolism is also necessary for the ras/MAPKinase signal tansduction pathway. Therefore, the use of Drosophila imaginal discs and brain and in particular the selDptuf mutation, provide an excellent model to investigate the role of selenoproteins in the regulation of cell proliferation, growth and differentiation.
An analysis of cancer prevention by selenium
Authors: Combs G. F. , Clark L. C. , Turnbull B. W.
Published: December 2008

The nutritional functions of selenium (Se) are recognized as being due to a number of Se‐containing proteins. It is not clear, however, whether any of these function in the anti‐tumorigenic effects of Se most of which have been demonstrated for Se exposures greater than those required for selenoprotein expression. Indeed, other anti‐tumorigenic mechanisms have been demonstrated for certain Se‐metabolites. The Nutritional Prevention of Cancer Trial found supplemental Se (200 μg/day, as Se‐enriched yeast) to be associated with significant reductions in cancer risks in subjects with pre‐treatment plasma Se concentrations below ca. 120 ng/ml (1.5 nmoles/ml), which level would appear to require food‐Se intakes of ca. 1.5 μg/kg body weight/day. However, the putative anti‐carcinogenic Se‐metabolite(s) should be more relevant than total plasma Se as a supplementation target for cancer prevention. These may be components of the non‐protein‐bound fraction of Se in plasma, which constitutes 2–4% of total plasma Se.
Cloning of Phospholipid Hydroperoxide Glutathione Peroxidase (PHGPx) as an anti‐apoptotic and growth promoting gene of Burkitt Lymphoma cells
Authors: Brielmeier M. , Béchet J.‐M. , Suppmann Sabine , Conrad M. , Laux G. , Bornkamm G. W.
Published: December 2008

Burkitt Lymphoma (BL) cells are highly sensitive to suboptimal growth conditions and undergo apoptosis when seeded at low cell density or reduced serum concentration. Irradiated fibroblasts or a mix of pruvate, α‐thioglycerol, and bathocuproine disulfonate can protect BL cells from apoptosis induced by lowering cell density or serum concentration by promoting cystine uptake in the cells. The availability of cystine is the limiting factor for glutathione biosynthesis in BL cells and thus for the ability of the cells to cope with oxidative stress. We have set up an expression cloning strategy to clone genes that protect BL cells from apoptosis induced by low cell density and/or serum. Using this approach we have cloned among others the cDNA for Phospholipid Hydroperoxide Glutathione Peroxidase (PHGPx).
Selenium (Se) from high‐selenium broccoli is utilized differently than selenite, selenate and selenomethionine, but is more effective in inhibiting colon carcinogenesis
Authors: Finley John W. , Davis Cindy D.
Published: December 2008

The reduction in incidence of chemically‐induced colon cancer by foods high in selenium (Se) was investigated in Fisher‐344 rats. The foods used were high‐Se broccoli (produced in a greenhouse by addition of selenate to the media surrounding the plant roots) and a processed high‐Se wheat product (made by milling high‐Se wheat purchased from a seleniferous area). Weanling rats were fed diets containing different amounts of Se from these foods or from selenium salts (selenite and selenate). Early in the experiment the animals were injected with a chemical carcinogen. After 11 weeks on diets animals were killed and the colons examined for preneoplastic lesions (aberrant crypts foci, ACF). ACF were significantly reduced in animals fed supra‐nutritional amounts of Se from broccoli, despite the finding that Se from broccoli was poorly bioavailable. Supra‐nutritional amounts of Se from high‐Se processed wheat also significantly reduced aberrant crypts (AC), although pure selenomethionine, (the predominant chemical form of Se in wheat), did not significantly reduce AC. These results emphasize the need to study Se in food forms, and not extrapolate from previous studies using pure chemical forms in cancer inhibition studies. They also demonstrate that foods with high Se bioavailability are not necessarily the most efficacious for cancer incidence reduction.
Glutathione peroxidase and viral replication: Implications for viral evolution and chemoprevention
Authors: Diamond Alan M. , Hu Ya Jun , Mansur David B.
Published: December 2008

It is likely that several of the biological effects of selenium are due to its effects on selenoprotein activity. While the effects of the anti‐oxidant selenoprotein glutathione peroxidase (GPx) on inhibiting HIV activation have been well documented, it is clear that increased expression of this enzyme can stimulate the replication and subsequent appearance of cytopathic effects associated with an acutely spreading HIV infection. The effects of GPx on both phases of the viral life cycle are likely mediated via its influence on signaling molecules that use reactive oxygen species, and similar influences on signaling pathways may account for some of the anti‐cancer effects of selenium. Similarly, selenium can alter mutagenesis rates in both viral genomes and the DNA of mammalian cells exposed to carcinogens. Comparisons between the effects of selenium and selenoproteins on viral infections and carcinogenesis may yield new insights into the mechanisms of action of this element.