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Cysteine Ligase (cysteine + ligase)

Distribution by Scientific Domains

Medical Sciences	50%

Selected Abstracts

Polyhydroxylated fullerene derivative C60(OH)24 prevents mitochondrial dysfunction and oxidative damage in an MPP+ -induced cellular model of Parkinson's disease

JOURNAL OF NEUROSCIENCE RESEARCH, Issue 16 2008
Xiaoqing Cai
Abstract To find effective agents for Parkinson's disease (PD) prevention and therapy, we examined the protective effects of the polyhydroxylated fullerene derivative C60(OH)24 in a 1-methyl-4-phenylpyridinium (MPP+)-induced acute cellular PD model in human neuroblastoma cells and the free radical scavenging effects in this model with an electron spin resonance (ESR) spectrometer. Pretreatment with C60(OH)24 at concentrations greater than 20 ,M showed significant protective effects on MPP+ -induced loss in cell viability, decreases in mitochondrial function (including mitochondrial membrane potential and activities of complex I and II), and increases in the levels of reactive oxygen species and oxidative damage to DNA and proteins. In addition, C60(OH)24 acts as a phase 2 enzyme inducer to protect cells from MPP+ -induced decreases in expression of nuclear factor-E2-related factor 2, expression and activity of ,-glutamyl cysteine ligase and level of glutathione. The ESR study showed that C60(OH)24 is a powerful radical scavenger for superoxide, hydroxyl, and lipid radicals. These data suggest that C60(OH)24 is a mitochondrial protective antioxidant with direct radical scavenging activity and indirect antioxidant inducing activity. © 2008 Wiley-Liss, Inc. [source]

Gender differences in glutathione metabolism in Alzheimer's disease

JOURNAL OF NEUROSCIENCE RESEARCH, Issue 6 2005
Honglei Liu
Abstract The mechanism underlying Alzheimer's disease (AD), an age-related neurodegenerative disease, is still an area of significant controversy. Oxidative damage of macromolecules has been suggested to play an important role in the development of AD; however, the underlying mechanism is still unclear. In this study, we showed that the concentration of glutathione (GSH), the most abundant intracellular free thiol and an important antioxidant, was decreased in red blood cells from male AD patients compared with age- and gender-matched controls. However, there was no difference in blood GSH concentration between the female patients and female controls. The decrease in GSH content in red blood cells from male AD patients was associated with reduced activities of glutamate cysteine ligase and glutathione synthase, the two enzymes involved in de novo GSH synthesis, with no change in the amount of oxidized glutathione or the activity of glutathione reductase, suggesting that a decreased de novo GSH synthetic capacity is responsible for the decline in GSH content in AD. These results showed for the first time that GSH metabolism was regulated differently in male and female AD patients. © 2005 Wiley-Liss, Inc. [source]

Extract of Ginkgo biloba induces glutamate cysteine ligase catalytic subunit (GCLC)

PHYTOTHERAPY RESEARCH, Issue 3 2008
Xiao-Ping Liu
Abstract The extract of Ginkgo biloba (EGb), containing 24% flavone glycosides and 6% terpenoids, is widely used to treat early-stage Alzheimer's disease, vascular dementia, peripheral claudication and vascular tinnitus. Its marked antioxidant activity has recently been demonstrated in both cell lines and animals. Glutathione (GSH) plays an important role in the antioxidant system by conjugating to xenobiotics to facilitate their export from cells. Glutamate cysteine ligase (GCL) is the rate-limiting enzyme for GSH synthesis and its catalytic subunit (GCLC) determines this de novo synthesis. Thus, induction of GCLC is a strategy to enhance the antioxidant capability in cells. The present study aimed to investigate the induction effect of EGb on GCLC in HepG2 and Hep1c1c7 cell lines. Real-time PCR, Western blot and enzyme activity assay were used to detect induction and it was found that GCLC was induced by EGb in these two cell lines. It is suggested that the antioxidant activity of EGb is (or is partly) through the induction of GCLC. Copyright © 2007 John Wiley & Sons, Ltd. [source]

Assessing oxidative pathway genes as risk factors for bipolar disorder

BIPOLAR DISORDERS, Issue 5 2010
Janice M Fullerton
Fullerton JM, Tiwari Y, Agahi G, Heath A, Berk M, Mitchell PB, Schofield PR. Assessing oxidative pathway genes as risk factors for bipolar disorder. Bipolar Disord 2010: 12: 550,556. © 2010 The Authors. Journal compilation © 2010 John Wiley & Sons A/S. Objectives:, There is a growing body of evidence implicating oxidative stress and the glutathione system in the pathogenesis of major psychiatric illnesses, including schizophrenia and bipolar disorder. Here we investigate whether genes involved in oxidative stress regulation are associated with increased risk for bipolar disorder. Methods:, Four candidate genes were selected a priori from two different steps in the oxidative stress pathway, specifically the synthesis of glutathione [catalytic subunit of glutamate cysteine ligase (GCLC) and regulatory subunit of glutamate cysteine ligase (GCLM)] and the removal of reactive oxygen species [superoxide dismutase 2 (SOD2) and glutathione peroxidase 3 (GPX3)]. Haplotype tagging and functional nucleotide polymorphisms were selected in each gene and tested for association with bipolar disorder under narrow (n = 240) and broad (n = 325) phenotypic models, compared to healthy controls (n = 392, comprising 166 psychiatrically assessed unaffected controls plus 226 healthy individuals). Results:, Single marker association analysis did not reveal significant association with bipolar disorder; however, haplotypes in the SOD2 gene showed nominal association (global ,2 = 8.94, p = 0.03; broad model). Interaction analysis revealed a significant interaction between SOD2 and GPX3 haplotypes, which further increases risk for bipolar disorder (odds ratio = 2.247, ,2 = 9.526, p = 0.002, corrected p = 0.029). Conclusions:, Further characterization of the SOD2 and GPX3 interaction using larger cohorts is required to determine the role of these oxidative pathway genes as risk factors for bipolar disorder. [source]