Biosynthesis and Functions of Glutathione, an Essential Biofactor

Meister, Alton

doi:10.3177/jnsv.38.special_1

Cited by 43 publications

(25 citation statements)

References 29 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The sulfhydryl group (−SH) of the cysteine is involved in reduction and conjugation reactions that are usually considered as the most important functions of GSH. These reactions provide the means for removal of peroxides and many xenobiotic compounds; however, GSH is also involved in regulation of the cell cycle (Meister 1992). …”

Section: Introductionmentioning

confidence: 99%

Glutathione: Overview of its protective roles, measurement, and biosynthesis

Forman

Rinna

2009

Molecular Aspects of Medicine

1,970

1,247

View full text Add to dashboard Cite

This review is the introduction to a special issue concerning, glutathione (GSH), the most abundant low molecular weight thiol compound synthesized in cells. GSH plays critical roles in protecting cells from oxidative damage and the toxicity of xenobiotic electrophiles, and maintaining redox homeostasis. Here, the functions and GSH and the sources of oxidants and electrophiles, the elimination of oxidants by reduction and electrophiles by conjugation with GSH are briefly described. Methods of assessing GSH status in the cells are also described. GSH synthesis and its regulation are addressed along with therapeutic approaches for manipulating GSH content that have been proposed. The purpose here is to provide a brief overview of some of the important aspects of glutathione metabolism as part of this special issue that will provide a more comprehensive review of the state of knowledge regarding this essential molecule.

show abstract

Section: Introductionmentioning

confidence: 99%

Glutathione: Overview of its protective roles, measurement, and biosynthesis

Forman

Rinna

2009

Molecular Aspects of Medicine

1,970

1,247

View full text Add to dashboard Cite

show abstract

“…Glutathione (GSH)1 is one of the major antioxidants synthesized in cells and plays key roles in maintaining redox homeostasis, scavenging peroxides, and detoxifying xenobiotics [19,20]. Recent studies have shown that resveratrol could increase GSH levels [10,11,14,21–25], suggesting that modulating the GSH homeostasis may play a significant role in the beneficial effects exhibited by resveratrol.…”

mentioning

confidence: 99%

Resveratrol and 4-hydroxynonenal act in concert to increase glutamate cysteine ligase expression and glutathione in human bronchial epithelial cells

Zhang¹,

Shih²,

Rinna³

et al. 2009

Archives of Biochemistry and Biophysics

View full text Add to dashboard Cite

Resveratrol has been shown to protect against oxidative stress through modulating antioxidant capacity. In this study, we investigated resveratrol-mediated induction of glutathione (GSH) and glutamate cysteine ligase (GCL), and the combined effect of resveratrol and 4-hydroxynonenal (HNE) on GSH synthesis in cultured HBE1 human bronchial epithelial cells. Resveratrol increased GSH and the mRNA contents of both the catalytic (GCLC) and modulatory subunit (GCLM) of GCL. Combined HNE and resveratrol treatment increased GSH content and GCL mRNAs to a greater extent than either compound did alone. Compared to individual agent, combining exposure to HNE and resveratrol also showed more protection against cell death caused by oxidative stress. These effects of combined exposure were additive rather than synergistic. In addition, Nrf2 silencing significantly decreased the combined effect of HNE and resveratrol on GCL induction. Our data suggest that resveratrol increases GSH and GCL gene expression and that there is an additive effect on GSH synthesis between resveratrol and HNE. The results also reveal that Nrf2-EpRE signaling was involved in the combined effects. KeywordsResveratrol; Glutathione; Glutamate cysteine ligase; EpRE; Combination effect; Nrf2; Signal transduction; 4-Hydroxynonenal; Antioxidant; Detoxifying enzyme Resveratrol, a polyphenolic compound ( Fig. 1) found in grapes, wine, berries, and herbal medicines such as Polygonum cuspidatum (Japanese knotweed), has been shown to have various beneficial effects including protection against cardiovascular disease and cancer [1][2][3][4]. The mechanism underlying these effects is under extensive investigation and multiple biological activities exhibited by resveratrol in regulating cell cycle [5], inducing apoptosis [6], stimulating endothelial nitric oxide synthase [7], and inhibiting platelet aggregation [8] have been demonstrated. Recently the antioxidant property of resveratrol has gained intense attention and studies have demonstrated that resveratrol could increase antioxidant capacity and efficiently protect against oxidative damage [9][10][11][12][13][14][15][16][17][18] Glutathione (GSH) 1 is one of the major antioxidants synthesized in cells and plays key roles in maintaining redox homeostasis, scavenging peroxides, and detoxifying xenobiotics [19,20]. Recent studies have shown that resveratrol could increase GSH levels [10,11,14,[21][22][23][24][25], suggesting that modulating the GSH homeostasis may play a significant role in the beneficial effects exhibited by resveratrol. Nonetheless, how resveratrol increases GSH level remains elusive. Furthermore, the concentrations used in most of these studies have been much higher than would be generally achievable in vivo.Glutamate cysteine ligase (GCL) catalyzes the formation of γ-glutamylcysteine and is the ratelimiting enzyme for de novo GSH synthesis. The gene expression of both the catalytic (GCLC) and modulatory (GCLM) subunit of GCL could be induced in response to various agents including poly...

show abstract

“…We would like to underline that GSH is the most important non-protein sulfhydryl molecule present in both prokaryotes and eukaryotes and is an important component of the antioxidant defence system in the living cells (Meister 1992). This thiol plays a vital role in the structure, activity and transport function of proteins, membranes and enzymes.…”

Section: Discussionmentioning

confidence: 99%

The role of TAMMEF therapy on the antioxidant status in osteoarthritis

et al. 2009

View full text Add to dashboard Cite

Osteoarthritis (OA) is the most common joint disorder, associated with loss of articular cartilage, osteophyte formation, subchodral bone change, synovitis and characterized by chronic and often disabling pain and stiffness of one or more joints. The pathogenesis of the disease is complex and still debated, even if recent studies have shown that reactive oxygen species may participate in the initiation and progression of OA. Moreover, it is known that pulsed electromagnetic fields are useful in the OA treatment, owing to their analgesic and anti-inflammatory properties. This work evaluated lipid peroxidation, glutathione, and ascorbic acid levels in patients with OA of spine, before and after the application of a new electromagnetic system, the TAMMEF (Therapeutic Application of a Musically Modulated Electromagnetic Field) system. In TAMMEF system, the extremely low frequencies electromagnetic field is piloted by a musical signal and its parameters (frequency, intensity, waveform) are modified in time, randomly varying within the respective ranges: so all possible codes can occur during a single application. Twenty patients affected by OA of spine and 20 healthy subjects were enrolled in this study. Plasma levels of ascorbic acid (AA), glutathione (GSH) and malondialdehyde (MDA) (as index of lipid peroxidation) were determined in patients and controls, before the beginning of treatment (first day of therapy) and at the end of cycle. All patients underwent a cycle of 10 daily sessions of 30 min each. Our study showed a significant increase of MDA level and a significant decrease of both AA and GSH levels in patients with OA compared to control group. These findings support the role of oxidative stress in the pathogenesis of OA. After TAMMEF treatment in the OA group, analysis revealed a significant decrease in plasma MDA and AA levels (P \ 0.05 and P \ 0.01, respectively), no significant difference in GSH levels. Reduction in MDA level could be due to the decreased generation of reactive oxygen species and/or to the increased detoxification activity mediated by GSH. No significant difference in GSH levels, evidenced in OA patients after TAMMEF treatment, could be due to effect sparing of AA on GSH. Furthermore, a beneficial symptomatic effect was observed in all patients.

show abstract

Biosynthesis and Functions of Glutathione, an Essential Biofactor

Cited by 43 publications

References 29 publications

Glutathione: Overview of its protective roles, measurement, and biosynthesis

Glutathione: Overview of its protective roles, measurement, and biosynthesis

Resveratrol and 4-hydroxynonenal act in concert to increase glutamate cysteine ligase expression and glutathione in human bronchial epithelial cells

The role of TAMMEF therapy on the antioxidant status in osteoarthritis

Contact Info

Product

Resources

About