Redox environment of the cell as viewed through the redox state of the glutathione disulfide/glutathione couple

Schäfer, Freya; Buettner, Garry R.

doi:10.1016/s0891-5849(01)00480-4

Cited by 4,048 publications

(3,464 citation statements)

References 148 publications

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“…This occurs despite the observed increase in NF‐ κ B activity, known to regulate the expression of several antioxidant proteins, including MnSOD (reviewed in Morgan and Liu 2011). H 2 O 2 can alter the redox state of the cell by either reacting directly with thiol residues within redox‐sensitive proteins or by shifting the GSH/GSSG ratio (Schafer and Buettner 2001). Detoxification of H 2 O 2 is achieved enzymatically by glutathione peroxidases, catalase, and peroxiredoxins.…”

Section: Discussionmentioning

confidence: 99%

Alterations in fatty acid metabolism and sirtuin signaling characterize early type-2 diabetic hearts of fructose-fed rats

et al. 2017

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Despite the fact that skeletal muscle insulin resistance is the hallmark of type‐2 diabetes mellitus (T2DM), inflexibility in substrate energy metabolism has been observed in other tissues such as liver, adipose tissue, and heart. In the heart, structural and functional changes ultimately lead to diabetic cardiomyopathy. However, little is known about the early biochemical changes that cause cardiac metabolic dysregulation and dysfunction. We used a dietary model of fructose‐induced T2DM (10% fructose in drinking water for 6 weeks) to study cardiac fatty acid metabolism in early T2DM and related signaling events in order to better understand mechanisms of disease. In early type‐2 diabetic hearts, flux through the fatty acid oxidation pathway was increased as a result of increased cellular uptake (CD36), mitochondrial uptake (CPT1B), as well as increased β‐hydroxyacyl‐CoA dehydrogenase and medium‐chain acyl‐CoA dehydrogenase activities, despite reduced mitochondrial mass. Long‐chain acyl‐CoA dehydrogenase activity was slightly decreased, resulting in the accumulation of long‐chain acylcarnitine species. Cardiac function and overall mitochondrial respiration were unaffected. However, evidence of oxidative stress and subtle changes in cardiolipin content and composition were found in early type‐2 diabetic mitochondria. Finally, we observed decreased activity of SIRT1, a pivotal regulator of fatty acid metabolism, despite increased protein levels. This indicates that the heart is no longer capable of further increasing its capacity for fatty acid oxidation. Along with increased oxidative stress, this may represent one of the earliest signs of dysfunction that will ultimately lead to inflammation and remodeling in the diabetic heart.

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Section: Discussionmentioning

confidence: 99%

Alterations in fatty acid metabolism and sirtuin signaling characterize early type-2 diabetic hearts of fructose-fed rats

et al. 2017

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“…The glutathione status represents the most important indicator of and determinant for the cellular redox environment (Schafer and Buettner 2001). Frozen tissue was ground in liquid nitrogen and the resulting powder homogenised in 1:10 (w:v) pre-cooled PCA (10% containing 2 mM bathophenantroline-disulphonic acid).…”

Section: Oxidative Stress Parametersmentioning

confidence: 99%

Effects of seasonal and latitudinal cold on oxidative stress parameters and activation of hypoxia inducible factor (HIF-1) in zoarcid fish

Heise

Estevez²,

Puntarulo³

et al. 2007

J Comp Physiol B

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Acute, short term cooling of North Sea eelpout Zoarces viviparus is associated with a reduction of tissue redox state and activation of hypoxia inducible factor (HIF-1) in the liver. The present study explores the response of HIF-1 to seasonal cold in Zoarces viviparus, and to latitudinal cold by comparing the eurythermal North Sea fish to stenothermal Antarctic eelpout (Pachycara brachycephalum). Hypoxic signalling (HIF-1 DNA binding activity) was studied in liver of summer and winter North Sea eelpout as well as of Antarctic eelpout at habitat temperature of 0°C and after long-term warming to 5°C. Biochemical parameters like tissue iron content, glutathione redox ratio, and oxidative stress indicators were analyzed to see whether the cellular redox state or reactive oxygen species formation and HIF activation in the fish correlate. HIF-1 DNA binding activity was significantly higher at cold temperature, both in the interspecific comparison, polar vs. temperate species, and when comparing winter and summer North Sea eelpout. Compared at the low acclimation temperatures (0°C for the polar and 6°C for the temperate eelpout) the polar fish showed lower levels of lipid peroxidation although the liver microsomal fraction turned out to be more susceptible to lipid radical formation. The level of radical scavenger, glutathione, was twofold higher in polar than in North Sea eelpout and also oxidised to over 50%. Under both conditions of cold exposure, latitudinal cold in the Antarctic and seasonal cold in the North Sea eelpout, the glutathione redox ratio was more oxidised when compared to the warmer condition. However, oxidative damage parameters (protein carbonyls and thiobarbituric acid reactive substances (TBARS) were elevated only during seasonal cold exposure in Z. viviparus. Obviously, Antarctic eelpout are keeping oxidative defence mechanisms high enough to avoid accumulation of oxidative damage products at low habitat temperature. The paper discusses how HIF could be instrumental in cold adaptation in fish.

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“…However compared to the control (medium-2), ascorbate does not change the level of GSH T . The lower levels of GSH T and ascorbate in HL-60 cells compared to U937 cells indicates that the redox environment [71] of HL-60 is more oxidized than in U937 cells suggesting that HL-60 cells may have a lower capacity to buffer an increased flux of ROS and thus they would have a higher sensitivity to ROS.…”

Section: Intracellular Gsh Asch − and Pdamentioning

confidence: 98%

“…Reduction of DHA to AscH − can be both, GSH-dependent or independent [65,70]. Glutathione is considered to be the principal redox buffer in the cell [71]. Depletion of GSH has been shown to increase the vulnerability of leukemia cells to exposure to ROS [72,73].…”

Section: Intracellular Gsh Asch − and Pdamentioning

confidence: 99%

Ascorbate enhances the toxicity of the photodynamic action of Verteporfin in HL-60 cells

Kramarenko

Wilke

Dayal

et al. 2006

Free Radical Biology and Medicine

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As a reducing agent, ascorbate serves as an antioxidant. However, its reducing function can in some settings initiate an oxidation cascade, i.e. appear to be a "pro-oxidant". This dichotomy also appears to hold when ascorbate is present during photosensitization. Ascorbate can react with singlet oxygen producing hydrogen peroxide. Thus, if ascorbate is present during photosensitization the formation of highly diffusible hydrogen peroxide could enhance the toxicity of the photodynamic action. On the other side, ascorbate could decrease toxicity by converting highly reactive singlet oxygen to less reactive hydrogen peroxide, which can be removed via peroxide-removing systems such as glutathione and catalase. To test the influence of ascorbate on photodynamic treatment we incubated leukemia cells (HL-60 and U937) with ascorbate and a photosensitizer (verteporfin, VP) and examined: AscH − uptake; levels of glutathione; changes in membrane permeability; cell growth; and toxicity. Accumulation of VP was similar in each cell line. Under our experimental conditions, HL-60 cells were found to accumulate less ascorbate and have lower levels of intracellular GSH compared to U937 cells. Without added ascorbate, HL-60 cells were more sensitive to VP and light treatment than U937 cells. When cells were exposed to VP and light ascorbate acted as an antioxidant in U937 cells, while it was a "pro-oxidant" for HL-60 cells. One possible mechanism to explain these observations is that HL-60 cells express myeloperoxidase activity, while in U937 cells it is below detection limit. Inhibition of myeloperoxidase activity with 4-aminobenzoic acid hydrazide (4-ABAH) had minimal influence on the phototoxicity of VP in HL-60 in the absence of ascorbate. However, 4-ABAH decreased the toxicity of ascorbate on HL-60 cells during VP-photosensitization, but had no affect on ascorbate toxicity in U937 cells. These data demonstrate that ascorbate increases hydrogen peroxide production by VP and light. This hydrogen peroxide activates MPO, producing toxic oxidants. These observations suggest that in some settings, ascorbate may enhance the toxicity of photodynamic action.

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Redox environment of the cell as viewed through the redox state of the glutathione disulfide/glutathione couple

Cited by 4,048 publications

References 148 publications

Alterations in fatty acid metabolism and sirtuin signaling characterize early type-2 diabetic hearts of fructose-fed rats

Alterations in fatty acid metabolism and sirtuin signaling characterize early type-2 diabetic hearts of fructose-fed rats

Effects of seasonal and latitudinal cold on oxidative stress parameters and activation of hypoxia inducible factor (HIF-1) in zoarcid fish

Ascorbate enhances the toxicity of the photodynamic action of Verteporfin in HL-60 cells

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