Cellular GSH Levels (cellular + gsh_level)

Distribution by Scientific Domains


Selected Abstracts


,-glutamylcysteine ethyl ester-induced up-regulation of glutathione protects neurons against A,(1,42)-mediated oxidative stress and neurotoxicity: Implications for Alzheimer's disease

JOURNAL OF NEUROSCIENCE RESEARCH, Issue 5 2005
Debra Boyd-Kimball
Abstract Glutathione (GSH) is an important endogenous antioxidant found in millimolar concentrations in the brain. GSH levels have been shown to decrease with aging. Alzheimer's disease (AD) is a neurodegenerative disorder associated with aging and oxidative stress. A,(1,42) has been shown to induce oxidative stress and has been proposed to play a central role in the oxidative damage detected in AD brain. It has been shown that administration of ,-glutamylcysteine ethyl ester (GCEE) increases cellular levels of GSH, circumventing the regulation of GSH biosynthesis by providing the limiting substrate. In this study, we evaluated the protective role of up-regulation of GSH by GCEE against the oxidative and neurotoxic effects of A,(1,42) in primary neuronal culture. Addition of GCEE to neurons led to an elevated mean cellular GSH level compared with untreated control. Inhibition of ,-glutamylcysteine synthetase by buthionine sulfoximine (BSO) led to a 98% decrease in total cellular GSH compared with control, which was returned to control levels by addition of GCEE. Taken together, these results suggest that GCEE up-regulates cellular GSH levels which, in turn, protects neurons against protein oxidation, loss of mitochondrial function, and DNA fragmentation induced by A,(1,42). These results are consistent with the notion that up-regulation of GSH by GCEE may play a viable protective role in the oxidative and neurotoxicity induced by A,(1,42) in AD brain. © 2005 Wiley-Liss, Inc. [source]


Schisandrin B stereoisomers protect against hypoxia/reoxygenation-induced apoptosis and associated changes in the Ca2+ -induced mitochondrial permeability transition and mitochondrial membrane potential in AML12 hepatocytes

PHYTOTHERAPY RESEARCH, Issue 11 2009
Po Yee Chiu
Abstract The effects of the schisandrin B stereoisomers, (±), -schisandrin [(±), -Sch] and (,)schisandrin B [(,)Sch B], on hypoxia/reoxygenation-induced apoptosis were investigated in AML12 hepatocytes. Changes in cellular reduced glutathione (GSH) levels, Ca2+ -induced mitochondrial permeability transitions (MPTs) and mitochondrial membrane potentials (,,m values) were also examined in (±), -Sch- and (,)Sch B-treated cells, without or with hypoxia/reoxygenation challenge. The (±), -Sch/(,)Sch B pretreatments (2.5,5.0 µm) protected against hypoxia/reoxygenation-induced apoptosis in AML12 cells in a concentration-dependent manner, with the (,)Sch B effect being more potent. Drug antiapoptotic effects were further evidenced by suppression of hypoxia/reoxygenation-induced mitochondrial cytochrome c release and subsequent cleavage of caspase 3 and poly-ADP-ribose polymerase by (,)Sch B pretreatment. Whereas hypoxia/reoxygenation challenge increased the extent of Ca2+ -induced MPT pore opening, and ,,m, in AML12 hepatocytes, cytoprotection afforded by (±), -Sch/(,)Sch B pretreatment against hypoxia/reoxygenation-induced apoptosis was associated with a decreased sensitivity to Ca2+ -induced MPT and an increased ,,m in both unchallenged and challenged cells, compared with the drug-free control. The results indicate that (±), -Sch/(,)Sch B pretreatment protected against hypoxia/reoxygenation-induced apoptosis in AML12 hepatocytes and that the cytoprotection afforded by (±), -Sch/(,)Sch B may at least in part be mediated by a decrease in sensitivity to Ca2+ -induced MPT, which may in turn result from enhancement of cellular GSH levels by drug pretreatments. Copyright © 2009 John Wiley & Sons, Ltd. [source]


Induction of glutathione synthesis in human keratinocytes by Ginkgo biloba extract (EGb761)

BIOFACTORS, Issue 1 2001
Gerald Rimbach
Abstract The 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 ,g/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 ,glutamylcysteinyl synthetase (,GCS), 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 ,GCS mRNA, protein and GSH may be an ubiquitous effect of EGb761 in mammalian cells. [source]