Plasma Membrane Redox System in the Control of Stress-Induced Apoptosis

Villalba, José M.; Navas, Plácido

doi:10.1089/ars.2000.2.2-213

Cited by 112 publications

(65 citation statements)

References 134 publications

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“…There are two other enzymes important for the intracellular metabolism of ascorbate, namely thioredoxin reductase and cytochrome-b5-reductase (48,49). There are several isoforms of thioredoxin reductase and cytochrome-b5-reductase in mice, but there is no commercial antibody to detect all of the different isoforms of these enzymes.…”

Section: Vitamin C Normalizes Gsh Metabolism In the Liver Of Wrn δHelmentioning

confidence: 99%

Vitamin C restores healthy aging in a mouse model for Werner syndrome

et al. 2009

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Werner syndrome (WS) is a premature aging disorder caused by mutations in a RecQ-like DNA helicase. Mice lacking the helicase domain of the WRN homologue exhibit many phenotypic features of WS, including a prooxidant status and a shorter mean life span compared to wild-type animals. Here, we show that Wrn mutant mice also develop premature liver sinusoidal endothelial defenestration along with inflammation and metabolic syndrome. Vitamin C supplementation rescued the shorter mean life span of Wrn mutant mice and reversed several age-related abnormalities in adipose tissues and liver endothelial defenestration, genomic integrity, and inflammatory status. At the molecular level, phosphorylation of age-related stress markers like Akt kinase-specific substrates and the transcription factor NF-κB, as well as protein kinase Cδ and Hif-1α transcription factor levels, which are increased in the liver of Wrn mutants, were normalized by vitamin C. Vitamin C also increased the transcriptional regulator of lipid metabolism PPARα. Finally, microarray and gene set enrichment analyses on liver tissues revealed that vitamin C decreased genes normally up-regulated in human WS fibroblasts and cancers, and it increased genes involved in tissue injury response and adipocyte dedifferentiation in obese mice. Vitamin C did not have such effect on wild-type mice. These results indicate that vitamin C supplementation could be beneficial for patients with WS.

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Section: Vitamin C Normalizes Gsh Metabolism In the Liver Of Wrn δHelmentioning

confidence: 99%

Vitamin C restores healthy aging in a mouse model for Werner syndrome

et al. 2009

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“…NQO1 is a NAD(P)H-dependent reductase that is translocated to the inner surface of the PM under stress conditions (30). Dietary CoQ is important in maintaining levels of reduced CoQ and ␣-tocopherol in the PM, thereby protecting the PM from lipid peroxidation (31). In the present study the effects of aging and CR on the brain PMRS and PM-associated oxidative stress were investigated in rats.…”

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confidence: 97%

Calorie restriction up-regulates the plasma membrane redox system in brain cells and suppresses oxidative stress during aging

Hyun

Emerson

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

249

160

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The plasma membrane (PM) contains redox enzymes that provide electrons for energy metabolism and recycling of antioxidants such as coenzyme Q and ␣-tocopherol. Brain aging and neurodegenerative disorders involve impaired energy metabolism and oxidative damage, but the involvement of the PM redox system (PMRS) in these processes is unknown. Caloric restriction (CR), a manipulation that protects the brain against aging and disease, increased activities of PMRS enzymes (NADH-ascorbate free radical reductase, NADH-quinone oxidoreductase 1, NADH-ferrocyanide reductase, NADH-coenzyme Q10 reductase, and NADH-cytochrome c reductase) and antioxidant levels (␣-tocopherol and coenzyme Q10) in brain PM during aging. Age-related increases in PM lipid peroxidation, protein carbonyls, and nitrotyrosine were attenuated by CR, levels of PMRS enzyme activities were higher, and markers of oxidative stress were lower in cultured neuronal cells treated with CR serum compared with those treated with ad libitum serum. These findings suggest important roles for the PMRS in protecting brain cells against age-related increases in oxidative and metabolic stress.Alzheimer's disease ͉ reactive oxygen species ͉ coenzyme Q10 ͉ oxidoreductase

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“…Inhibition of the PMOR in q°cells (Larm et al 1994), and other cell lines , causes cell death, highlighting its vital role in redox homeostasis. The PMOR also modulates cellular processes that are redox sensitive, including cell growth, intracellular signaling and apoptosis (reviewed in Baker and Lawen 2000), and it maintains plasma membrane antioxidant systems, preventing oxidative stress-induced cell death (reviewed in Villalba and Navas 2000). Although the PMOR has been extensively studied in non-neuronal cells, to our knowledge, studies of the PMOR in primary CNS neurons have not been reported.…”

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confidence: 99%

CNS neurons express two distinct plasma membrane electron transport systems implicated in neuronal viability

Wright

Kühn

2002

Journal of Neurochemistry

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Trans-plasma membrane electron transport is critical for maintaining cellular redox balance and viability, yet few, if any, investigations have studied it in intact primary neurons. In this investigation, extracellular reduction of 2,6-dichloroindophenol (DCIP) and ferricyanide (FeCN) were measured as indicators of trans-plasma membrane electron transport by chick forebrain neurons. Neurons readily reduced DCIP, but not FeCN unless CoQ 1 , an exogenous ubiquinone analog, was added to the assays. CoQ 1 stimulated FeCN reduction in a dosedependent manner but had no effect on DCIP reduction. Reduction of both substrates was totally inhibited by e-maleimidocaproic acid (MCA), a membrane-impermeant thiol reagent, and slightly inhibited by superoxide dismutase. Diphenylene iodonium, a flavoenzyme inhibitor, completely inhibited FeCN reduction but had no affect on DCIP reduction, suggesting that these substrates are reduced by distinct redox pathways. The relationship between plasma membrane electron transport and neuronal viability was tested using the inhibitors MCA and capsaicin. MCA caused a dose-dependent decline in neuronal viability that closely paralleled its inhibition of both reductase activities. Similarly capsaicin, a NADH oxidase inhibitor, induced a rapid decline in neuronal viability. These results suggest that trans-plasma membrane electron transport helps maintain a stable redox environment required for neuronal viability.

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Plasma Membrane Redox System in the Control of Stress-Induced Apoptosis

Cited by 112 publications

References 134 publications

Vitamin C restores healthy aging in a mouse model for Werner syndrome

Vitamin C restores healthy aging in a mouse model for Werner syndrome

Calorie restriction up-regulates the plasma membrane redox system in brain cells and suppresses oxidative stress during aging

CNS neurons express two distinct plasma membrane electron transport systems implicated in neuronal viability

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