Zur Biochemie der Thiolgruppe: Bedeutung des Glutathions

Sies, Helmut

doi:10.1007/bf00396705

Cited by 59 publications

(15 citation statements)

References 96 publications

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“…It has been reported that some thiol compounds, such as GSH and N-acetylcysteine (NAC), can protect cells from oxidative stress by scavenging free radicals and by enzymatic reactions. Glutathione is the most important cellular thiols, modulating redox-regulated signal transduction, acting as a substrate for several peroxidases and other enzymes that prevent or mitigate the deleterious effects of ROS [44], [45]. The ratio of GSH/GSSG in the plasma can reflect changes in the stability of the redox status of an organism [46].…”

Section: Discussionmentioning

confidence: 99%

Celastrol Prevents Atherosclerosis via Inhibiting LOX-1 and Oxidative Stress

Wei

et al. 2013

PLoS ONE

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Celastrol is a triterpenoid compound extracted from the Chinese herb Tripterygium wilfordii Hook F. Previous research has revealed its anti-oxidant, anti-inflammatory, anti-cancer and immunosuppressive properties. Here, we investigated whether celastrol inhibits oxidized low-density lipoprotein (oxLDL) induced oxidative stress in RAW 264.7 cells. In addition, the effect of celastrol on atherosclerosis in vivo was assessed in apolipoprotein E knockout (apoE−/−) mouse fed a high-fat/high-cholesterol diet (HFC). We found that celastrol significantly attenuated oxLDL-induced excessive expression of lectin-like oxidized low density lipoprotein receptor-1(LOX-1) and generation of reactive oxygen species (ROS) in cultured RAW264.7 macrophages. Celastrol also decreased IκB phosphorylation and degradation and reduced production of inducible nitric oxide synthase (iNOS), nitric oxide (NO) and proinflammatory cytokines such as tumor necrosis factor (TNF)-α and IL-6. Celastrol reduced atherosclerotic plaque size in apoE−/− mice. The expression of LOX-1 within the atherosclerotic lesions and generation of superoxide in mouse aorta were also significantly reduced by celastrol while the lipid profile was not improved. In conclusion, our results show that celastrol inhibits atherosclerotic plaque developing in apoE−/− mice via inhibiting LOX-1 and oxidative stress.

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Section: Discussionmentioning

confidence: 99%

Celastrol Prevents Atherosclerosis via Inhibiting LOX-1 and Oxidative Stress

Wei

et al. 2013

PLoS ONE

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“…GSH also conjugates with electrophiles and thus participates in the metabolism and detoxification of endogenous compounds and xenobiotic toxicants [14–16]. In addition, GSH is involved in many other metabolic reactions [9, 17, 18]. Therefore, it is not surprising that GSH plays roles in various cellular processes such as cell growth, proliferation, and apoptosis.…”

Section: Introductionmentioning

confidence: 99%

Glutathione synthesis and its role in redox signaling

Zhang¹,

Forman²

2012

Seminars in Cell & Developmental Biology

194

100

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Glutathione (GSH) is the most abundant antioxidant and a major detoxification agent in cells. It is synthesized through two-enzyme reaction catalyzed by glutamate cysteine ligase and glutathione synthetase, and its level is well regulated in response to redox change. Accumulating evidence suggests that GSH may play important roles in cell signaling. This review will focus on the biosynthesis of GSH, the reaction of S-glutathionylation (the conjugation of GSH with thiol residue on proteins), GSNO, and their roles in redox signaling.

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“…Apart from its function as an antioxidant, it is responsible for the maintenance of intracellular thiol redox status and thus for the function of many biological processes within the cell [3,4]. For most of its functions glutathione must be in the reduced form.…”

Section: Introductionmentioning

confidence: 99%

Molecular characterization and expression of Onchocerca volvulus glutathione reductase

Müller

Gilberger

Fairlamb

et al. 1997

Biochemical Journal

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Glutathione metabolism represents a potential target for anti-parasite drug design. The central role of glutathione reductase (GR) in maintenance of the thiol redox state and in anti-oxidative defence has to be evaluated in more detail in order to establish the essential function of this enzyme for the survival of the filarial parasite Onchocerca volvulus. The O. volvulus GR (OvGR) gene was cloned and sequenced. The gene is composed of 13 exons and 12 introns and spans 4065 bp. The first intron is located within the 5′-untranslated region of the gene, 16 nucleotides upstream of the translation initiation codon. Southern-blot analysis and structural characterization of the genomic sequence indicate that OvGR is encoded by a single-copy gene. Isolation of various cDNA clones revealed a polymorphism of polyadenylation initiation with no consensus polyadenylation sites in any of the cDNAs analysed. The entire cDNA is 1977 bp long and carries the nematode-specific spliced leader sequence SL1 at its 5′ end, 236 nucleotides upstream of the first in-frame methionine. The cDNA codes for a polypeptide of 462 amino acids with 53.5% sequence identity with human GR (HsGR). A total of 18 out of 19 residues contributing to glutathione binding are identical in OvGR and HsGR. However, one of the arginine residues (Arg-224 in HsGR) involved in discrimination between NADPH and NADH in all known GRs is substituted by tryptophan (Trp-207 in OvGR). The coding region of OvGR was expressed in Escherichia coli as a histidine-fusion protein, and it was established that the parasite protein still favours the binding of NADPH (Km 10.9 μM) over NADH (Km 108 μM). The histidine-fusion protein has a subunit size of 54 kDa and is active as a homodimer of 110 kDa.

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Zur Biochemie der Thiolgruppe: Bedeutung des Glutathions

Cited by 59 publications

References 96 publications

Celastrol Prevents Atherosclerosis via Inhibiting LOX-1 and Oxidative Stress

Celastrol Prevents Atherosclerosis via Inhibiting LOX-1 and Oxidative Stress

Glutathione synthesis and its role in redox signaling

Molecular characterization and expression of Onchocerca volvulus glutathione reductase

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