bluuebunny/crossref_metadata_2025_split huggingface dataset:
Protective effects of antioxidants on age‐related changes in the electrophoretic patterns of cardiac LDH, hepatic ALP and serum proteins in male golden hamster
Authors: El‐Zayat Emad , Amin Amer Sayed 
Published: May 2003

AbstractBasal and antioxidant‐induced changes in the isoenzyme and isoform patterns of cardiac lactate dehydrogenase (EC 1.1.1.27) and hepatic alkaline phosphatase (EC 3.1.3.1), respectively, as well as the electrophoretic patterns of serum proteins in different age groups of male golden hamster were compared. This is to test whether age‐induced changes could be corrected by long‐term administration of antioxidants. Data indicated that aging causes no remarkable change in the total activity of either cardiac LDH or hepatic ALP, however a significant increase in the fractional activity of some cardiac LDH isoenzymes and a significant reduction in the fractional activity of some hepatic ALP isoforms were induced by aging. On the other hand, long‐term administration of antioxidants appeared to manifest a clear counteracting effect on the age‐related changes in old age. This effect was indicated in the fractional activity of cardiac LDH isoenzymes and of hepatic ALP isoforms. The present study has also shown a wide‐range variation in serum protein patterns due to aging and/or antioxidant administration, which indirectly reflect a parallel variation in the process of gene expression and/or proteolytic activity. Copyright © 2003 John Wiley & Sons, Ltd.
Sodium selenite modulates tumour marker indices in N‐nitrosodiethylamine‐initiated and phenobarbital‐promoted rat liver carcinogenesis
Authors: Thirunavukkarasu C. , Sakthisekaran D. 
Published: May 2003

AbstractThe effect of sodium selenite (Se) was investigated against two‐stage rat liver carcinogenesis initiated by a single intraperitoneal injection of N‐nitrosodiethylamine (DEN, 200 mg kg−1 i.p.) followed by promotion with phenobarbital (PB, 0.05%) in a basal diet. Se (4 p.p.m.) was administered per os daily throughout the entire experiment, before the initiation, or during the promotion stage. The plasma, liver (hepatoma and surrounding tissue) and kidney tissue were investigated biochemically for lactate dehydrogenase, aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase and 5′‐nucleotidase. These enzyme activities were increased (p < 0.001) in plasma of hepatoma‐bearing rats compared with normal control rats. The elevation of these enzyme activities in plasma was indicative of the persistent deteriorating effect of DEN in cancer‐bearing animals. Aminotransferase levels were decreased in hepatoma and surrounding liver tissue, whereas lactate dehydrogenase, alkaline phosphatase and 5′‐nucleotidase were increased in the cancer condition. These enzyme activities were reversed to near normal control values in animals treated with Se. It is apparent that the beneficial effect of Se is primarily exerted on the initiation phase and secondarily during the promotion stage of DEN‐initiated rat liver carcinogenesis. The analysis of marker enzyme activities taken together with our previous findings clearly indicates the antitumour efficacy of sodium selenite on DEN‐induced hepatoma animals. Copyright © 2003 John Wiley & Sons, Ltd.
Arachidonic acid cytotoxicity: can arachidonic acid be a physiological mediator of cell death?
Authors: Pompeia Celine , Lima Thais , Curi Rui 
Published: May 2003

AbstractArachidonic acid is a polyunsaturated fatty acid that mediates inflammation and the functioning of several organs and systems either directly or upon its conversion into eicosanoids. However, arachidonic acid is found to be cytotoxic in vitro at concentrations that overlap physiological ones. It is tempting therefore to speculate that arachidonic acid may be a physiological inducer of apoptosis and that such cytotoxic action may be another of its roles in vivo. Nevertheless its pro‐inflammatory and oxidative stress‐inducing features are characteristic of necrosis and pathological conditions. We hereby review the cytotoxic action of arachidonic acid, indicate the possible pathways that lead to cell death and contemplate the cytotoxic role of arachidonic acid in vivo. Copyright © 2003 John Wiley & Sons, Ltd.
Experimental researches on the role of phosphoinositide‐specific phospholipase C in 4‐hydroxynonenal induced exocytosis
Authors: Maggiora Marina , Armida Rossi Maria 
Published: May 2003

AbstractThe action of 4‐hydroxynonenal (HNE), a chemotactic aldehyde produced by lipid peroxidation, was analysed on exocytosis in parallel with its effects on phosphoinositide‐specific phospholipase C (PLC) both in undifferentiated HL‐60 cells and in cells induced to differentiate toward the granulocytic cell line by 1.25% DMSO. Exocytosis was evaluated by the secretion of β‐glucuronidase from cells incubated at 37°C for 10 min in the presence of various aldehyde concentrations. HNE action was more pronounced in DMSO‐differentiated cells, where concentrations between 10−8 and 10−6 m were able both to trigger exocytosis and to strongly activate PLC; in both processes maximal stimulation was given by 10−7 m. HNE‐induced exocytosis was completely prevented by pertussis toxin and by the PLC inhibitor U73122. The comparison between HNE and formyl‐methionyl‐leucyl‐phenylalanine (fMLP), used as a positive control, showed that the tripeptide produced an higher stimulation of exocytosis than the aldehyde; by contrast HNE induced a stronger increase of PLC activity. Wortmannin, an inhibitor of phosphatidylinositol‐3‐kinase (PI3K), strongly inhibited the exocytosis induced by fMLP, while it failed to induce a statistically significant inhibition of HNE action. We conclude that both compounds trigger exocytosis through a Ptx‐sensitive G protein; the present data support the hypothesis that the lower ability of the aldehyde to trigger exocytosis as compared to fMLP might depend upon a low ability to activate PI3K, while PLC activation appears to play a key role in HNE‐induced exocytosis. Copyright © 2003 John Wiley & Sons, Ltd.
Trypsin induces tumour necrosis factor‐α secretion from a human leukemic mast cell line
Authors: Kang Ok‐Hwa , Jeong Hyun‐Ja , Kim Dae‐Ki , Choi Suck‐Chei , Kim Tae‐Hyun , Nah Yong‐Ho , Kim Hyung‐Min , Lee Young‐Mi 
Published: May 2003

AbstractTrypsin activating both proteinase‐activated receptor (PAR) 2 and PAR4 plays an important role in inflammation. We have investigated the potential of trypsin to induce TNF‐α secretion from the human leukemic mast cell line (HMC‐1). HMC‐1 cells co‐express both PAR2 and PAR4, and their agonist trypsin signals to HMC‐1 cells. Trypsin (100 nm), SLIGKV‐NH2 (100 μm, corresponding to the PAR2 tethered ligand), or GYPGQV‐NH2 (100 μm, corresponding to the PAR4 tethered ligand) induced tumour necrosis factor (TNF)‐α secretion from HMC‐1 cells. TNF‐α secretion by trypsin was significantly blocked by pretreatment with 50 μm PD098059, MEK‐1 inhibitor. Furthermore, trypsin stimulated the activation of extracellular signal‐regulated kinase (ERK) in HMC‐1 cells without any detectable activation of c‐Jun N‐terminal kinase (JNK) and p38 MAP kinase homologue. These results show that trypsin may induce TNF‐α secretion following activation of ERK via both PAR2 and PAR4 on HMC‐1 cells. Copyright © 2003 John Wiley & Sons, Ltd.
Effects of vitamin E on microsomal Ca2+‐ATPase activity and calcium levels in streptozotocin‐induced diabetic rat kidney
Authors: Doǧru Pekiner Bilgehan , Daş Evcimen Net , Ulusu Nuray N. , Bali Musa , Karasu Çimen 
Published: May 2003

AbstractVitamin E treatment has been found to be beneficial in preventing or reducing diabetic nephropathy. Increased tissue calcium and abnormal microsomal Ca2+‐ATPase activity have been suggested as contributing factors in the development of diabetic nephropathy. This study was undertaken to test the hypothesis that vitamin E reduces lipid peroxidation and can prevent the abnormalities in microsomal Ca2+‐ATPase activity and calcium levels in kidney of streptozotocin (STZ)‐induced diabetic rats. Male rats were rendered diabetic by a single STZ injection (55 mg kg−1 i.p.). After diabetes was verified, diabetic and age‐matched control rats were untreated or treated with vitamin E (400–500 IU kg−1 day−1, orally) for 10 weeks. Ca2+‐ATPase activity and lipid peroxidation (MDA) were determined spectrophotometrically. Blood glucose levels increased approximately five‐fold (> 500 mg dl−1) in untreated‐diabetic rats but decreased to 340±27 mg dl−1 in the vitamin E treated‐diabetic group. Kidney MDA levels did not significantly change in the diabetic state. However, vitamin E treatment markedly inhibited MDA levels in both control and diabetic animals. Ca2+‐ATPase activity was 0.483±0.008 U l−1 in the control group and significantly increased to 0.754±0.010 U l−1 in the STZ‐diabetic group (p < 0.001). Vitamin E treatment completely prevented the diabetes‐induced increase in Ca2+‐ATPase activity (0.307±0.025 U l−1, p < 0.001) and also reduced the enzyme activity in normal control rats. STZ‐diabetes resulted in approximately two‐fold increase in total calcium content of kidney. Vitamin E treatment led to a significant reduction in kidney calcium levels of both control and diabetic animals (p < 0.001). Thus, vitamin E treatment can lower blood glucose and lipid peroxidation, which in turn prevents the abnormalities in kidney calcium metabolism of diabetic rats. This study describes a potential biochemical mechanism by which vitamin E supplementation may delay or inhibit the development of cellular damage and nephropathy in diabetes. Copyright © 2003 John Wiley & Sons, Ltd.
The inhibitory effect of BSP‐A1/‐A2 on protein kinase C and tyrosine protein kinase
Authors: Yu Bingzhi , Zhao Yongmei , Zhao Wei , Chen Fei , Liu Ying , Zhang Jie , Fu Wei , Zong Zhihong , Yu Aiming , Guan Yi 
Published: May 2003

AbstractBovine seminal plasma contains a group of similar proteins, namely BSP‐A1, BSP‐A2, BSP‐A3, and BSP‐30‐kDa (collectively called BSP proteins), and they are secreted by the seminal vesicles. In our study, we purified the BSP‐A1/‐A2 through affinity chromatography and found for the first time that BSP‐A1/‐A2 can inhibit the activity of protein kinase C (PKC) and tyrosine protein kinase (TPK). The inhibition was dose dependent. When the PKC and TPK activities are expressed as the logarithm of percentage activity taking the activity in the absence of the BSP‐A1/‐A2 as 100%, there is a linear relationship between the their activities and the dose of BSP‐A1/‐A2. Copyright © 2003 John Wiley & Sons, Ltd.
Prolonged effect of a single serotonin treatment in adult age on the serotonin and histamine content of white blood cells and mast cells of rats
Authors: Csaba G. , Kovács P. , Pállinger Éva 
Published: May 2003

AbstractHormonal imprinting was provoked by serotonin treatment in adult age. Three weeks after treatment with 100 μg serotonin, the serotonin and histamine content of peritoneal cells (mast cells, lymphocytes and the monocyte–macrophage–granulocyte group), white blood cells (lymphocytes, granulocytes and monocytes) and thymic lymphocytes was studied by flow cytometry. The content of both amines was significantly higher in the mast cells of males and lower in females. Blood lymphocytes contained a higher serotonin and histamine level in males, and a lower serotonin level in females. The peritoneal monocyte–macrophage–granulocyte group contained less serotonin in both males and females. Thymocytes contained higher levels of both amines in females and higher histamine level in males. The experiments demonstrate that a single treatment at adult age can provoke imprinting, which alters—in the present case—the serotonin and histamine content of immune cells durably. Copyright © 2003 John Wiley & Sons, Ltd.
Effects of indomethacin on the divisional morphogenesis and cytoskeleton‐dependent processes of Tetrahymena
Authors: Kovács Péter , Pállinger Éva 
Published: May 2003

AbstractIndomethacin (0.1 mM) causes significantly altered phospholipid synthesis in Tetrahymena and is able to influence the inositol phospholipid signalling system.9 In the present study the effects of indomethacin on the course of cell division, cyclin expression, the cortical microtubular system and on cytoskeleton‐dependent processes (motility, phagocytosis) were investigated. As expected from its interference with the synthesis of phospholipids, indomethacin affected Tetrahymena in a number of ways: the structure of the cortical microtubular system became irregular; in many cells the stomatogenesis (development of new oral apparatus) and the development of the fission furrow was not accompanied by elongation of the macronucleus, which is a typical phenomenon of the normal course of mitosis: apparently indomethacin uncouples these phenomena. After indomethacin treatment, the expression of both cyclin A and cyclin B1 were reduced significantly. The cell growth rate, motility and phagocytotic activity were all considerably reduced. There are probably additional mechanisms responsible for the effect of indomethacin on the systems that control divisional morphogenesis, for microtubule‐dependent processes and for the connection between nuclear and cortical alterations during the cell cycle. Effects on protein phosphorylation/dephosphorylation, on cyclin expression and on microtubular functions are probably involved. These possibilities are discussed. Copyright © 2003 John Wiley & Sons, Ltd.
Comparison of the Chemical Properties of Iron and Cobalt Porphyrins and Corrins
Authors: Jensen Kasper P. , Ryde Ulf 
Published: May 2003

AbstractDensity functional calculations have been used to compare various geometric, electronic and functional properties of iron and cobalt porphyrin (Por) and corrin (Cor) species. The investigation is focussed on octahedral MII/III complexes (where M is the metal) with two axial imidazole ligands (as a model of b and c type cytochromes) or with one imidazole and one methyl ligand (as a model of methylcobalamin). However, we have also studied some five‐coordinate MII complexes with an imidazole ligand and four‐coordinate MI/II complexes without any axial ligands as models of other intermediates in the reaction cycle of coenzyme B12. The central cavity of the corrin ring is smaller than that of porphine. We show that the cavity of corrin is close to ideal for low‐spin CoIII, CoII, and CoI with the axial ligands encountered in biology, whereas the cavity in porphine is better suited for intermediate‐spin states. Therefore, the low‐spin state of Co is strongly favoured in complexes with corrins, whereas there is a small energy difference between the various spin states in iron porphyrin species. There are no clear differences for the reduction potentials of the octahedral complexes, but [CoICor] is more easily formed (by at least 40 kJ mole−1) than [FeIPor]. Cobalt and corrin form a strong CoC bond that is more stable against hydrolysis than iron and porphine. Finally, FeII/III gives a much lower reorganisation energy than CoII/III; this is owing to the occupied d orbital in CoII. Altogether, these results give some clues about how nature has chosen the tetrapyrrole rings and their central metal ion.
Signaling Effects of Demethylasterriquinone B1, a Selective Insulin Receptor Modulator
Authors: Webster Nicholas J. G. , Park Kaapjoo , Pirrung Michael C. 
Published: May 2003

AbstractA possible breakthrough in the treatment of diabetes was made with the discovery that a fungal natural product, demethylasterriquinone B1 (DAQ B1), is an orally active, small‐molecule mimic of insulin. Subsequent work has shown that the glucose‐lowering effects of DAQ B1 are not accompanied by enhanced vascular proliferation, which is a side effect of chronic insulin administration that can lead to arteriosclerosis. Our recent short and modular total synthesis of DAQ B1 could be readily modified to create congeners and afforded ample supplies of the natural product, which permitted intracellular signal transduction of DAQ B1 to be examined. The activities of DAQ B1 and over a dozen related structures were studied for insulin receptor (IR) and insulin receptor substrate‐1 phosphorylation. Examination of the effect of DAQ B1 on kinases downstream of the IR in insulin signal transduction showed selective activation of Akt kinase (a metabolic effect) but not of extracellular‐regulated kinase (a proliferative effect). The influence of DAQ B1 on gene expression (determined by a microarray study) was also divergent from that of insulin, which activates both proliferative and metabolic pathways. The action of DAQ B1 as a selective insulin receptor modulator can be accounted for by its ability to selectively activate one kinase among the many emanating from insulin receptor autophosphorylation and its reduced effects on gene expression.
Indolocarbazole Glycosides in Inactive Conformations
Authors: Facompré Michaël , Carrasco Carolina , Vezin Hervé , Chisholm John D. , Yoburn Joshua C. , Van Vranken David L. , Bailly Christian 
Published: May 2003

AbstractIndolocarbazole glycosides related to rebeccamycin represent a promising category of antitumor agents targeting DNA and topoisomerase I. These drugs prefer to adopt a closed conformation with an intramolecular hydrogen bond between the indole NH group and the pyranose oxygen atom. Three pairs of indolocarbazole monoglycosides bearing an NH or an N‐methyl indole moiety were synthesized and their biological properties investigated at the molecular and cellular level. Replacing the indole NH proton with a methyl group reduces DNA interaction and abolishes activity against DNA topoisomerase I. Surface plasmon resonance studies performed with a pair of water‐soluble indolocarbazole glycosides and two hairpin oligonucleotides containing an [AT]4 or a [CG]4 sequence indicate that both the NH and the N‐methyl derivative maintain a relatively high affinity for DNA (Keq=2–6×105 M−1) but the incorporation of the methyl group restricts access to the DNA. The number of ligand binding sites (n) on the oligonucleotides is about twice as high for the NH compound compared to its N‐methyl analogue. Modeling and 1H NMR studies demonstrate that addition of the N‐methyl group drives a radical change in conformation in which the orientation of the aglycone relative to the β‐glucoside is reversed. The loss of the closed conformation by the N‐methyl derivatives perturbs thir ability to access DNA binding sites and prevents the drug from inhibiting topoisomerase I. As a consequence, the NH compounds exhibit potent cytotoxicity against CEM leukemia cells with an IC50 value in the 1 μM range, whereas the N‐methyl analogues are 10 to 100 times less cytotoxic. These studies offer circumstantial evidence supporting the importance of the closed conformation in the interaction of indolocarbazole glycosides with their molecular targets, DNA and topoisomerase I.
Monitoring the Cellular Surface Display of Recombinant Proteins by Cysteine Labeling and Flow Cytometry
Authors: Jose Joachim , Handel Steffen 
Published: May 2003

AbstractA general method is described that allows one to follow the surface display of recombinant proteins in Escherichia coli without having to use specific antibodies or enzymatic reactions. The method is based on cysteine‐specific labeling through Michael addition to the double bond of maleimide and its derivatives, and takes advantage of the fact that naturally occurring surface proteins in E. coli contain no accessible cysteine residues. The method is easy to perform and could be simply applied to different analytic procedures including Western blot, spectral photometry, and flow cytometry. By using this new labeling method, single cells bearing a distinct protein at the surface could be selected by fluorescence‐activated cell sorting. The data were obtained by using autodisplay, an efficient surface display system established for E. coli, but the method presented here represents rather a general solution for analyzing the surface display of recombinant proteins, independent of the cellular system used.
Aspartic Proteases Involved in Alzheimer's Disease
Authors: Schmidt Boris 
Published: May 2003

AbstractAlzheimer's disease afflicts every tenth human aged over 65. Despite the dramatic progress that has been made in understanding the disease, the exact cause of Alzheimer's disease is still unknown. Most gene mutations associated with Alzheimer's disease point at the same culprits: amyloid precursor protein and ultimately amyloid β. The enigmatic proteases α‐,β‐, and γ‐secretase are the three executioners of amyloid precursor protein processing, and disruption of their delicate balance is suspected to result in Alzheimer's disease. Significant progress has been made in the selective control of these proteases, regardless of the availability of structural information. Not even the absence of a robust cell‐free assay for γ‐secretase could hamper the identification of nonpeptidic inhibitors of this enzyme for long. Within five years, four distinctly different structural moieties were developed and the first drug candidates are in clinical trials. Unfortunately, selective inhibition of amyloid β formation remains a crucial issue because fundamental fragments of the γ‐secretase complex are important for other signaling events. This problem makes β‐secretase inhibition and α‐secretase induction even more appealing.
Large‐Scale In Vivo Synthesis of the Carbohydrate Moieties of Gangliosides GM1 and GM2 by Metabolically Engineered Escherichia coli
Authors: Antoine Tatiana , Priem Bernard , Heyraud Alain , Greffe Lionel , Gilbert Michel , Wakarchuk Warren W. , Lam Joseph S. , Samain Eric 
Published: May 2003

AbstractTwo metabolically engineered Escherichia coli strains have been constructed to produce the carbohydrate moieties of gangliosides GM2 (GalNAcβ‐4(NeuAcα‐3)Galβ‐4Glc; Gal=galactose, Glc=glucose, Ac=acetyl) and GM1 (Galβ‐3GalNAcβ‐4(NeuAcα‐3)Galβ‐4Glc. The GM2 oligosaccharide‐producing strain TA02 was devoid of both β‐galactosidase and sialic acid aldolase activities and overexpressed the genes for CMP‐NeuAc synthase (CMP=cytidine monophosphate), α‐2,3‐sialyltransferase, UDP‐GlcNAc (UDP=uridine diphosphate) C4 epimerase, and β‐1,4‐GalNAc transferase. When this strain was cultivated on glycerol, exogenously added lactose and sialic acid were shown to be actively internalized into the cytoplasm and converted into GM2 oligosaccharide. The in vivo synthesis of GM1 oligosaccharide was achieved by taking a similar approach but using strain TA05, which additionally overexpressed the gene for β‐1,3‐galactosyltransferase. In high‐cell‐density cultures, the production yields for the GM2 and GM1 oligosaccharides were 1.25 g L−1 and 0.89 g L−1, respectively.