bluuebunny/crossref_metadata_2025_split huggingface dataset:
Functions of GI‐GPx: Lessons from selenium‐dependent expression and intracellular localization
Authors: Brigelius‐Flohé R. , Müller C. , Menard J. , Florian S. , Schmehl K. , Wingler K. 
Published: December 2008

AbstractGastro intestinal glutathione peroxidase (GI‐GPx) is one of the four distinct mammalian selenoperoxidases. It had been reported to be restricted to the gastrointestinal tract but has more recently been identified also in human liver and some tumor cell lines. GI‐GPx ranks high in the hierarchy of selenoproteins. The GI‐GPx mRNA rather increases than decreases in selenium deficiency. GI‐GPx protein responds poorly to selenium deprivation and increases fast upon resupplementation. Putative biological roles of GI‐GPx, e.g. protection against food‐born hydroperoxides, redox‐regulation of proliferation or apoptosis, and modulation of mucosal immunity, are discussed in the light of cellular and subcellular distribution, transcriptional regulation and observations with k.o. mice.
Selenoproteins in human thyroid tissues
Authors: Zagrodzki Paweł , Nicol Fergus , Arthur John R. , Słowiaczek Marian 
Published: December 2008

AbstractThe aim of the present work was to clarify whether the activities of selenoenzymes can serve as markers for different tumors or goiters, as classified by histological criteria. The following parameters were determined: 1) selenium content of plasma (Se), 2) activities of the selenoenzymes: plasma glutathione peroxidase (plGSHPx), cytosolic glutathione peroxidase (cGSHPx), type I and type II iodothyronine deiodinases (ID‐I, ID‐II), thioredoxin reductase (THRR) in human thyroid tissues. The material came from follicular neoplasm, papillary carcinoma, struma nodosa, struma lymphomatosis Hashimoto, other thyroid surgery specimens, and normal tissues. There was no difference in Se nor in plGSHPx between patients and healthy volunteers. No significant differences were found for any parameter in thyroid carcinoma versus normal or goitrous thyroid tissue. In the whole group of thyroid surgery specimens the statistically significant correlations were found between ID‐I and ID‐II and between THRR and selenoperoxidases. Principal components analysis confirmed the above correlation and moreover revealed correlation between Se and plGSHPx, but did not detect any clear distinction between patients with the different diagnoses.
Induction of glutathione synthesis in human keratinocytes by Ginkgo biloba extract (EGb761)
Authors: Rimbach Gerald , Gohil Kishorchandra , Matsugo Seiichi , Moini Hadi , Virgili Claude Saliou, Fabio , Weber Packer Stefan U. , Lester 
Published: December 2008

AbstractThe objective of the present study was to characterize the action of Ginkgo biloba extract (EGb761) and its sub‐fractions on glutathione homeostasis in a human keratinocyte cell culture model. Cells were incubated with EGb761, its purified flavonoid (quercetin, kaempferol, rutin) or terpenoids (gingkolides A, B, C, J, bilobalide) constituents or the vehicle for up to 72 hours. Incubation of keratinocytes with the purified flavonoids or terpenoids did not affect cellular GSH levels. However, EGb761 treatment (up to 200 μg/ml) resulted in a dose‐dependent increase of cellular GSH. Western blot analysis of extracts from cells treated with EGb761 revealed increased levels of the catalytic subunit of γglutamylcysteinyl synthetase (γGCS), the rate‐limiting enzyme in GSH synthesis. The abundance of mRNA for the catalytic subunit (assayed by RT‐PCR) was also increased by the treatment with EGb761. Increased levels of cellular GSH by EGb761 were also observed in other cell lines including those from human bladder and liver as well as in murine macrophages indicating that the induction of γGCS mRNA, protein and GSH may be an ubiquitous effect of EGb761 in mammalian cells.
Cholesterol oxidation products and fibrogenesis
Authors: Leonarduzzi Gabriella , Sevanian Alex , Poli Giuseppe 
Published: December 2008

AbstractOxidatively modified low density lipoproteins (oxLDL) are known to affect various cellular processes by modulating molecolar transduction pathways and signaling nuclear transcription [1,2]. In particular, the proinflammatory and proatherosclerotic effects of oxLDL are increasingly supported by a multitude of independent but consistent experimental studies. LDL oxidation might be a sequencial process where their lipid moieties are progressively but discretely oxidized, preceding the oxidation/modification of the apolipoprotein domain, an effect that can ultimately result in the uncontrolled uptake of these particles by cells, such as macrophages, and conversion of them to foam cells which is a hallmark of early atherogenesis [3]. These lipoproteins appear to trigger a variety of events which are strongly implicated in the atherogenesis, the pathological process underlying vascular disease.
Curcumin differentially regulates TGF‐β1, its receptors and nitric oxide synthase during impaired wound healing
Authors: Mani Haresh , Sidhu Gurmel S. , Kumari Ranjana , Gaddipati Jaya P. , Seth Pankaj , Maheshwari Radha K. 
Published: December 2008

AbstractWound healing is a highly ordered process, requiring complex and coordinated interactions involving peptide growth factors of which transforming growth factor‐beta (TGF‐β) is one of the most important. Nitric oxide is also an important factor in healing and its production is regulated by inducible nitric oxide synthase (iNOS). We have earlier shown that curcumin (diferuloylmethane), a natural product obtained from the plant Curcuma longa, enhances cutaneous wound healing in normal and diabetic rats. In this study, we have investigated the effect of curcumin treatment by topical application in dexamethasone‐impaired cutaneous healing in a full thickness punch wound model in rats. We assessed healing in terms of histology, morphometry, and collagenization on the fourth and seventh days post‐wounding and analyzed the regulation of TGF‐β1, its receptors type I (tIrc) and type II (tIIrc) and iNOS. Curcumin significantly accelerated healing of wounds with or without dexamethasone treatment as revealed by a reduction in the wound width and gap length compared to controls. Curcumin treatment resulted in the enhanced expression of TGF‐β1 and TGF‐β tIIrc in both normal and impaired healing wounds as revealed by immunohistochemistry. Macrophages in the wound bed showed an enhanced expression of TGF‐β1 mRNA in curcumin treated wounds as evidenced by in situ hybridization. However, enhanced expression of TGF‐β tIrc by curcumin treatment observed only in dexamethasone‐impaired wounds at the 7th day post‐wounding. iNOS levels were increased following curcumin treatment in unimpaired wounds, but not so in the dexamethasone‐impaired wounds. The study indicates an enhancement in dexamethasone impaired wound repair by topical curcumin and its differential regulatory effect on TGF‐β1, it's receptors and iNOS in this cutaneous wound‐healing model.
Characteristic rat tissue accumulation of nobiletin, a chemopreventive polymethoxyflavonoid, in comparison with luteolin
Authors: Murakami Akira , Koshimizu Koichi , Ohigashi Hajime , Kuwahara Shigeru , Kuki Wataru , Takahashi Yasuo , Hosotani Keisuke , Kawahara Satsuki , Matsuoka Yumi 
Published: December 2008

AbstractNobiletin (NOB), a polymethoxyflavonoid, is an effective anti‐inflammatory and chemopreventive phytochemical found in citrus fruits. We compared the absorption and metabolism characteristics of NOB with those of luteolin (LT) in male SD rats. Each flavonoid (67.1 μmol/kg of body weight) was given separately by gastric intubation, and then concentrations were measured at 1, 4, and 24 hours after administration. In the digestive organs, NOB showed a notable tendency for localizing into the mucous membrane and muscularis from 1 to 4 hours, in contrast to LT, though both NOB and LT were completely excreted within 24 hours. Further, significant amounts of NOB were detected in the whole liver and kidney specimens, whereas LT accumulation was slight. Although serum concentrations of NOB from 1 to 4 hours were comparable to those of LT, urinary concentrations of LT were significantly higher from 4 to 24 hours. Following glucuronidase/sulfatase treatments of urinary materials, we detected 3 types of mono‐demethylated NOB, including 3′‐demethyl‐NOB, and two di‐demethylated types, as well as 3′‐demethyl‐NOB alone in serum samples using liquid chromatography‐mass spectral analysis. Our results suggest that the metabolic properties of polymethoxyflavonoids are distinct from those of other general flavonoids, because of their wide distribution and accumulation in tissue.
Impact of water‐dispersible beadlets as a vehicle for the delivery of carotenoids to cultured cells
Authors: Shahrzad Siranoush , Cadenas Enrique , Sevanian Alex , Packer Lester 
Published: December 2008

AbstractWater‐dispersible beadlets of carotenoids were used as supplements for human umbilical vein endothelial cells (HUVECs), human peripheral blood mononuclear cells (PBMCs) and human monocytes. Stability, cellular association and cytotoxicity of the carotenoid beadlets were compared with carotenoids delivered with tetrahydrofuran (THF). Incubations with lycopene, β‐carotene, lutein and astaxanthin dissolved in THF resulted in a lower stability in the medium, lower cellular association, and a higher standard deviation. Beadlets provided 60, 4, 6, and 2 times greater accumulation of lycopene, β‐carotene, lutein and astaxanthin, respectively, by PBMCs than THF. The cellular association of carotenoids delivered by THF seems to be more carotenoid‐specific than when carotenoids are delivered by beadlets. After 48∼h of incubation under cell culture conditions all of the four carotenoids (1 μM) delivered by beadlets to the medium showed a reduction less than 30%. In addition, no cytotoxic effect of the carotenoid beadlets or the vehicle alone was detected in a concentration range of 0.5‐5 μM. The results show that beadlets are a non‐toxic vehicle for supplementing and stabilizing carotenoids in culture media offering a reasonable compromise in term of cell accumulation efficiency.
Amelioration of cisplatin toxicity by a fermented grain food product
Authors: Minamiyama Yukiko , Takemura Shigekazu , Toyokuni Shinya , Nishino Yoshihiro , Yamasaki Keiichi , Hai Seikan , Yamamoto Satoshi , Okada Shigeru 
Published: December 2008

AbstractThe most noticeable hypothesis regarding the pathogenesis of cisplatin toxicity, seen mainly in kidney and intestine, is oxidative stress, an imbalance between free‐radical generating cisplatin and radical scavenging systems. This paper describes the role of the antioxidant system in cisplatin‐induced toxicity and the protective effect by a processed grain food (Antioxidant Biofactor: AOB®), which has been shown to exhibit strong antioxidant activity.Male Fischer 344 rats were used. They were pre‐fed either a basal diet (control, 15 g/day) or the diet supplemented with AOB® to provide 6.5% or 20% of total diet throughout the experiment. Cisplatin (5 mg/kg, i.v.) was administered at the start of the experiment, and the animals were sacrificed 5 days later. Blood urea nitrogen (BUN) and plasma creatinine, NO2‐} and NO3−(NOx) were determined from the plasma. The levels of 4‐hydroxy‐2‐nonenal (a lipid peroxidation product), 8‐hydroxy‐deoxyguanosine (8‐OHdG, an oxidatively modified DNA adduct) and nitrotyrosine were histologically analyzed. The cisplatin administration resulted in a loss of body weight and elevations of BUN, serum creatinine and NOx levels, whereas AOB supplement reversed these effects. The severe morphological damages induced in the kidney and intestine by the cisplatin administration were markedly improved in the AOB group. The levels of lipid peroxidation, 8‐OHdG, and nitrotyrosine all paralleled the morphological damage. The AOB effect was dose dependent. In conclusion, the present study suggests that certain food additives like AOB may be of benefit against the side effects of cisplatin.
Glutathione transport in the endo/sarcoplasmic reticulum
Authors: Csala Miklós , Fulceri Rosella , Mandl József , Benedetti Angelo , Bánhegyi Gábor 
Published: December 2008

AbstractGlutathione transport through the endo/sarcoplasmic reticulum (ER/SR) membrane might play a role in the maintenance of the thiol redox potential difference between the lumen and the cytosol.The transport of glutathione (both GSH and glutathione disulfide, GSSG) is entirely different in the ER and SR membranes.The transport measurements based on either rapid filtration or light scattering techniques revealed that the SR membrane transports glutathione much faster than the hepatic ER membrane or microsomal membranes prepared from heart or brain. The fastest transport has been measured in the membrane of muscle terminal cisternae, which is enriched in ryanodine receptor type 1 (RyR1). All the studied membranes have been found to be equally impermeable to various hydrophilic substances of similar size to glutathione, thus the glutathione transport in muscle microsomes and terminal cysternae as well as the correlation between the rate of glutathione transport and the abundance of RyR1 are specific. In both muscle microsomes and terminal cysternae, glutathione influx can be either inhibited or activated by antagonists and agonists of the ryanodine receptor, respectively, while these agents do not influence the transport of other small permeant molecules. These findings strongly suggest that the ryanodine receptor channel activity is directly associated with glutathione transport activity in the skeletal muscle sarcoplasmic reticulum membrane.
Multidrug resistance‐associated proteins: Export pumps for conjugates with glutathione, glucuronate or sulfate
Authors: Homolya László , Váradi András , Sarkadi Balázs 
Published: December 2008

AbstractMany endogenous or xenobiotic lipophilic substances are eliminated from the cells by the sequence of oxidation, conjugation to an anionic group (glutathione, glucuronate or sulfate) and transport across the plasma membrane into the extracellular space. The latter step is mediated by integral membrane glycoproteins belonging to the superfamily of ATP‐Binding Cassette (ABC) transporters. A subfamily, referred as ABCC, includes the famous/infamous cystic fibrosis transmembrane regulator (CFTR), the sulfonylurea receptors (SUR 1 and 2), and the multidrug resistance‐associated proteins (MRPs). The name of the MRPs refers to their potential role in clinical multidrug resistance, a phenomenon that hinders the effective chemotherapy of tumors. The MRPs that have been functionally characterized so far share the property of ATP‐dependent export pumps for conjugates with glutathione (GSH), glucuronate or sulfate. MRP1 and MRP2 are also mediating the cotransport of unconjugated amphiphilic compounds together with free GSH. MRP3 preferentially transports glucuronides but not glutathione S‐conjugates or free GSH. MRP1 and MRP2 also contribute to the control of the intracellular glutathione disulfide (GSSG) level. Although these proteins are low affinity GSSG transporters, they can play essential role in response to oxidative stress when the activity of GSSG reductase becomes rate limiting. The human MRP4, MRP5 and MRP6 have only partially been characterized. However, it has been revealed that MRP4 can function as an efflux pump for cyclic nucleotides and nucleoside analogues, used as anti‐HIV drugs. MRP5 also transports GSH conjugates, nucleoside analogues, and possibly heavy metal complexes. Transport of glutathione S‐conjugates mediated by MRP6, the mutation of which causes pseudoxantoma elasticum, has recently been shown. In summary, numerous members of the multidrug resistance‐associated protein family serve as export pumps that prevent the accumulation of anionic conjugates and GSSG in the cytoplasm, and play, therefore, an essential role in detoxification and defense against oxidative stress.
Reduction of the endoplasmic reticulum accompanies the oxidative damage of diabetes mellitus
Authors: Nardai Gábor , Korcsmáros Tamás , Papp Eszter , Csermely Péter 
Published: December 2008

AbstractThe endoplasmic reticulum (ER), similary to other subcompartments of the eukaryotic cell possesses a relatively oxidizing environment. The special milieu of ER lumen is important for many ER‐specific processes (redox protein folding, glycoprotein synthesis, quality control of secreted proteins, antigen presentation, etc.). Despite of the vital importance of redox regulation in the ER, we have a surprisingly fragmented knowledge about the mechanisms responsible for the ER redox balance. Moreover, new observations on disulfide bridge synthesis and on glutathione functions urge us to revise our recent theories based on many indirect and in vitro results. We have also very little information about the effects of different pathological conditions on the thiol metabolism and redox folding in the ER. Examining the role of molecular chaperones in the cellular pathology of diabetes mellitus we found that the ER redox environment shifted to a more reducing state, which was followed by changes of the thiol metabolism and structural‐functional changes of the protein machinery involved in the redox folding process in diabetes. The possible consequences of these unexpected changes are also discussed.
Structural and functional organization of Complex I in the mitochondrial respiratory chain
Authors: Bianchi Cristina , Fato Romana , Genova Maria Luisa , Castelli Giovanna Parenti , Lenaz Giorgio 
Published: December 2008

AbstractMetabolic flux control analysis of NADH oxidation in bovine heart submitochondrial particles revealed high flux control coefficients for both Complex I and Complex III, suggesting that the two enzymes are functionally associated as a single enzyme, with channelling of the common substrate, Coenzyme Q. This is in contrast with the more accepted view of a mobile diffusable Coenzyme Q pool between these enzymes. Dilution with phospholipids of a mitochondrial fraction enriched in Complexes I and III, with consequent increased theoretical distance between complexes, determines adherence to pool behavior for Coenzyme Q, but only at dilution higher than 1:5 (protein:phospholipids), whereas, at lower phospholipid content, the turnover of NADH cytochrome c reductase is higher than expected by the pool equation.
Regulation of coenzyme Q biosynthesis and breakdown
Authors: Dallner Gustav , Brismar Kerstin , Chojnacki Tadeusz , Swiezewska Ewa 
Published: December 2008

AbstractAll animal cells synthesize sufficient amounts of coenzyme Q (CoQ) and the cells also possess the capacity to metabolize the lipid. The main product of the metabolism is an intact ring with a short carboxylated side chain which glucuronidated in the liver and excreted mainly into the bile (Nakamura et al., Biofactors 9 (1999), 111–119). In other cells CoQ is phosphorylated, transferred into the blood and excreted through the urine. The biosynthesis of this lipid is regulated by nuclear receptors. PPARα is not required for the biosynthesis, or induction upon cold exposure, but it is necessary for the elevated CoQ synthesis during peroxisomal induction. RXRα is involved in the basal synthesis of CoQ and also in the increased synthesis upon cold treatment but is not required for peroxisomal induction. Dietary CoQ in human appear in the blood and it is taken up by mononuclear but not polynuclear cells. The former cells display a specific phospholipid modification, an increase of arachidonic acid content. In monocytes the CoQ administration leads to a significant decrease of the β2‐integrin CD11b and the complement receptor CD35. CD11b is one of the adhesion factors regulating the entry of these cells into the arterial wall which demonstrates that the anti‐atherogenic effect of CoQ is mediated by other mechanisms beside its antioxidant protection.
Specificity of Coenzyme Q inhibition of an aging‐related cell surface NADH oxidase (ECTO‐NOX) that generates superoxide
Authors: Morré Dorothy M. , James Morré D. 
Published: December 2008

AbstractOur laboratories have described a novel class of ectoproteins at the cell surface with both NADH or hydroquinone oxidase (NOX) and protein disulfide‐thiol interchange activities (ECTO‐NOX proteins). The two activities exhibited by these proteins alternate to generate characteristic patterns of oscillations where the period length is independent of temperature. The period length for the constitutive ECTO‐NOX is 24 min. Here we describe a distinctive age‐related ECTO‐NOX (arNOX) whose activity is blocked by coenzyme Q10. arNOX occurs exclusively in aged cells and tissues. The period length of the oscillations is 26 min. Rather than reducing 1/2 O2 to H2O, electrons are transferred to O2 to form superoxide. Superoxide formation was demonstrated by superoxide dismutase‐sensitive reduction of ferricytochrome c and by reduction of a superoxide‐specific tetrazolium salt. Quinone inhibition was given by coenzymes Q8, 9 and Q10 but not by Q0, Q2, Q4, Q6 or 7. The arNOX provides a mechanism to propagate reactive oxygen species generated at the cell surface to surrounding cells and circulating lipoproteins of importance to atherogenesis. Inhibition of arNOX by dietary coenzyme Q10 provides a rational basis for dietary coenzyme 10 use to retard aging‐related arterial lesions.
Effect of UV‐C mediated oxidative stress in leukemia cell lines and its relation to ubiquinone content
Authors: Brugè F. , Tiano L. , Cacciamani T. , Principi F. , Littarru G. P. 
Published: December 2008

AbstractUV‐C radiation is able to impair cellular functions by directly damaging DNA, and by inducing an increased formation of reactive oxygen species that leads to a condition of oxidative stress. In this study we evaluated different responses to UV insult of two leukemia cell lines, HL‐60 and Raji, and the relationship with their CoQ10 content. DNA damage was monitored by means of the alkaline single cell gel electrophoresis (Comet assay); intracellular levels of ROS, mitochondrial depolarization and cell viability was measured by flow cytometry. Raji cells appeared more resistant to the UV insult; moreover, they did not show any increase in ROS content and the extent of mitochondrial depolarisation was much lower than in HL 60 cell line. Raji cells also contained significantly higher levels of CoQ10 and their ability to incorporate and to reduce exogenous CoQ10 added to the culture medium was remarkably elevated compared with HL 60.
Coenzyme Q10 reduces the toxicity of rotenone in neuronal cultures by preserving the mitochondrial membrane potential
Authors: Menke T. , Gille G. , Reber F. , Janetzky B. , Andler W. , Funk R. H. W. , Reichmann H. 
Published: December 2008

AbstractDefects in mitochondrial energy metabolism due to respiratory chain disorders lead to a decrease in mitochondrial membrane potential (ΔΨm) and induce apoptosis. Since coenzyme Q10 (CoQ10) plays a dual role as an antioxidant and bioenergetic agent in the respiratory chain, it has attracted increasing attention concerning the prevention of apoptosis in mitochondrial diseases. In this study the potential of CoQ10 to antagonize the apoptosis‐inducing effects of the respiratory chain inhibitor rotenone was explored by video‐enhanced microscopy in SH‐SY5Y neuroblastoma cells. The cationic fluorescent dye JC‐1 which exhibits potential‐dependent accumulation in mitochondria was used as an indicator to monitor changes in ΔΨm. The relative changes in fluorescence intensity after incubation with rotenone for 15 minutes were calculated. Pre‐treatment with CoQ10 (10 or 100 μM) for 48h led to a significant reduction of rotenone‐induced loss of ΔΨm. These results suggest, that cytoprotection by CoQ10 may be mediated by raising cellular resistance against the initiating steps of apoptosis, namely the decrease of ΔΨm. Whether these data may provide new directions for the development of neuroprotective strategies has to be investigated in future studies.