Cyclic strain modulates resistance to oxidant stress by increasing G6PDH expression in smooth muscle cells

Leopold, Jane A.; Loscalzo, Joseph

doi:10.1152/ajpheart.2000.279.5.h2477

Cited by 57 publications

(50 citation statements)

References 37 publications

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Section: Mayr Et Al Pkc␦ In Smcsmentioning

confidence: 78%

“…[42][43][44] Importantly, enhanced apoptosis after mechanical injury is associated with a decrease in GSH levels, 45 and the response of SMCs to mechanical strain is modulated by glucose 6-phosphate dehydrogenase activity. 23 Therefore, our mechanistic data provide a better explanation of why PKC␦ Ϫ/Ϫ SMCs are resistant to apoptosis and contribute to accelerated neointima formation in PKC␦ Ϫ/Ϫ vein grafts.In summary, the present study provides new insights into PKC␦ isoform specific effects, which could not have been obtained by studying individual signaling pathways. Our integrated approach highlights the intimate connections between glucose metabolism and susceptibility to cell death, and identifies PKC␦ as one of the key kinases in vascular SMCs, ideally positioned to serve as a "sentinel" responding to abnormalities in glucose metabolism, oxidative stress, and cytoskeleton rearrangement.…”

mentioning

confidence: 78%

“…21,22 GSH is a tripeptide with a free sulfhydryl group and is of paramount importance in maintaining the reducing intracellular environment. 21,23 Consequently, increased GSH protected PKC␦ Ϫ/Ϫ SMCs against oxidative stress-induced cell death: treatment with 100 mol/L diethylmaleate (DEM), a sulfhydrylreactive agent, resulted in rapid depletion of GSH ( Figure 6A), followed by a drop in ATP levels ( Figure 6B) and cell death in PKC␦ ϩ/ϩ SMCs ( Figure 6C). In contrast, PKC␦ -/-SMCs were less sensitive to DEM-induced cell death ( Figure 6A to C), tolerating up to 20-times higher concentrations of DEM than PKC␦ ϩ/ϩ SMCs (data not shown).…”

Section: Elevated Glutathione Levels Protect Pkc␦ ؊/؊ Smcsmentioning

confidence: 99%

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Proteomic and Metabolomic Analysis of Vascular Smooth Muscle Cells

Mayr

Siow

Chung

et al. 2004

Circulation Research

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Abstract-Recent developments of proteomic and metabolomic techniques provide powerful tools for studying molecular mechanisms of cell function. Previously, we demonstrated that neointima formation was markedly increased in vein grafts of PKC␦-deficient mice compared with wild-type controls. To clarify the underlying mechanism, we performed a proteomic and metabolomic analysis of cultured vascular smooth muscle cells (SMCs) derived from PKC␦ ϩ/ϩ and PKC␦ Ϫ/Ϫ mice. Using 2-dimensional electrophoresis and mass spectrometry, we identified Ͼ30 protein species that were altered in PKC␦ Ϫ/Ϫ SMCs, including enzymes related to glucose and lipid metabolism, glutathione recycling, chaperones, and cytoskeletal proteins. Interestingly, nuclear magnetic resonance spectroscopy confirmed marked changes in glucose metabolism in PKC␦ Ϫ/Ϫ SMCs, which were associated with a significant increase in cellular glutathione levels resulting in resistance to cell death induced by oxidative stress. Furthermore, PKC␦ Ϫ/Ϫ SMCs overexpressed RhoGDI␣, an endogenous inhibitor of Rho signaling pathways. Inhibition of Rho signaling was associated with a loss of stress fiber formation and decreased expression of SMC differentiation markers. Thus, we performed the first combined proteomic and metabolomic study in vascular SMCs and demonstrate that PKC␦ is crucial in regulating glucose and lipid metabolism, controlling the cellular redox state, and maintaining SMC differentiation. (Circ Res. 2004;94:e87-e96.)Key Words: proteomics Ⅲ metabolomics Ⅲ smooth muscle cells Ⅲ PKC Ⅲ signal transduction P roteomic and metabolomic techniques are ideal for clarifying quantitative protein and metabolite changes in physiological and diseased conditions, respectively. [1][2][3][4][5] In vascular research, however, proteomics and metabolomics are still in their infancies 6 -8 and no studies have been performed so far comparing proteomic and metabolomic profiles in vascular smooth muscle cells (SMCs).PKC␦ represents a novel PKC isoform as characterized on the basis of its structure and maximal activation by diacylglycerol in the absence of calcium. 9,10 We recently developed knockout mice lacking PKC␦ and studied its effect on neointima formation in vein grafts. 11 We demonstrated that loss of PKC␦ markedly accelerated neointima formation, resulting in complete occlusion of the vessel lumen in one-third of the vein grafts. As with p53-deficient mice, 12 neointimal lesions in PKC␦ Ϫ/Ϫ vein grafts contained twice as many SMCs as wild-type controls and showed significantly lower numbers of apoptotic SMCs. 11 In vitro experiments revealed that SMCs derived from PKC␦ Ϫ/Ϫ mice were less sensitive to various apoptotic stimuli, including cytokine treatment. Their apoptotic resistance appeared to involve a loss of free radical generation as evidenced by redoxsensitive fluorescent dyes. 11 Besides modulating apoptosis, PKC␦ was found to be important for cytoskeleton rearrangement and cell migration. 13 However, the molecular mechanisms of resistance to apoptosis and cyt...

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Section: Mayr Et Al Pkc␦ In Smcsmentioning

confidence: 78%

mentioning

confidence: 78%

Section: Elevated Glutathione Levels Protect Pkc␦ ؊/؊ Smcsmentioning

confidence: 99%

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Proteomic and Metabolomic Analysis of Vascular Smooth Muscle Cells

Mayr

Siow

Chung

et al. 2004

Circulation Research

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“…In this context, glucose-6-phosphate dehydrogenase (G6PD) has been proposed as a cell enzyme aiding in survival against oxidative stress by generating NADPH required for GSH regeneration (Leopold & Loscalzo 2000, Filosa et al 2003, Jiang et al 2003, Díaz-Flores et al 2006. G6PD activity increases in growing cells and prevents cell death during oxidative stress (Tian et al 1998(Tian et al , 1999; hence, its inhibition brings about a drop in NADPH levels, a decrease in cell growth (Endo et al 1993), and an exacerbation of damage caused by free radicals (Filosa et al 2003).…”

Section: Introductionmentioning

confidence: 99%

Changes in the glucose-6-phosphate dehydrogenase activity in granulosa cells during follicular atresia in ewes

et al. 2009

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Apoptosis of granulosa cells during follicular atresia is preceded by oxidative stress, partly due to a drop in the antioxidant glutathione (GSH). Under oxidative stress, GSH regeneration is dependent on the adequate supply of NADPH by glucose-6-phosphate dehydrogenase (G6PD). In this study, we analyzed the changes of G6PD, GSH, and oxidative stress of granulosa cells and follicular liquid and its association with apoptosis during atresia of small (4-6 mm) and large (O6 mm) sheep antral follicles. G6PD activity was found to be higher in granulosa cells of healthy small rather than large follicles, with similar GSH concentration in both cases. During atresia, increased apoptosis and protein oxidation, as well as a drop in GSH levels, were observed in follicles of both sizes. Furthermore, the activity of G6PD decreased in atretic small follicles, but not in large ones. GSH decreased and protein oxidation increased in follicular fluid. This was dependent on the degree of atresia, whereas the changes in G6PD activity were based on the type of follicle. The higher G6PD activity in the small follicles could be related to granulosa cell proliferation, follicular growth, and a lower sensitivity to oxidative stress when compared with large follicles. The results also indicate that GSH concentration in atretic follicles depends on other factors in addition to G6PD, such as de novo synthesis or activity of other NADPH-producing enzymes. Finally, lower G6PD activity in large follicles indicating a higher susceptibility to oxidative stress associated to apoptosis progression in follicle atresia.

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“…The role of GR is fundamental for GPX activity, maintaining the cytosolic concentration of reduced glutathione [27,28], and therefore involved in detoxification reactive oxygen. Peroxidases decompose hydrogen peroxide and organic hydroperoxides produced during normal metabolism and also prevents peroxideinduced DNA damage, lipid peroxidation, and protein degradation [29].…”

Section: Determination Of the Enzymatic Activity Of Antioxidantsmentioning

confidence: 99%

Evaluation of Acetaminophen Effect on Oxidative Stressed Mice by Peroxide Hydrogen

Zoubair¹,

Azzahra²,

Hmimid³

et al. 2013

AJBR

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Acetaminophen (Paracetamol) is among the most commonly used analgesic and antipyretic drugs worldwide, it's often, but anomalously, classified as non-steroidal anti-inflammatory drugs (NSAIDs) in textbooks of pharmacology [1,2]. This study aims to evaluate if paracetamol has an antioxidant effect, relative to its analgesic antipyretic and weak anti-inflammatory activities, or it possesses a cytotoxic potential. Oxidative stress was induced by intraperetoneal injection of peroxide hydrogen (H 2 O 2 ), and then a comparative study is made concerning the activities of the antioxidant enzymes SOD, CAT, and GR as well as lipid peroxidation levels in liver. An increase in SOD, CAT, GR activity and lipid peroxidation in mice treated with H 2 O 2 accompanied by paracetamol; compared to the group treated by vitamin C + H 2 O 2 showed that acetaminophen doesn't show any antioxidant effect. Moreover this study has suggested that acetaminophen induced cytotoxicity in liver mediated by increased oxidative stress and altered redox metabolism. Keywords: acetaminophen (paracetamol), peroxide hydrogen, oxidative stressCite This Article: BENKHASSI Zoubair, LAHLOU Fatima Azzahra, HMIMID Fouzia, LOUTFI Mohammed, BENAJI Brahim, and BOURHIM Noureddine, "Evaluation of Acetaminophen Effect on Oxidative Stressed Mice by Peroxide Hydrogen

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Cyclic strain modulates resistance to oxidant stress by increasing G6PDH expression in smooth muscle cells

Cited by 57 publications

References 37 publications

Proteomic and Metabolomic Analysis of Vascular Smooth Muscle Cells

Proteomic and Metabolomic Analysis of Vascular Smooth Muscle Cells

Changes in the glucose-6-phosphate dehydrogenase activity in granulosa cells during follicular atresia in ewes

Evaluation of Acetaminophen Effect on Oxidative Stressed Mice by Peroxide Hydrogen

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