Hyperglycemia and oxidative stress: complex relationships with attractive prospects

Leverve, Xavier

doi:10.1007/s00134-002-1629-3

Cited by 46 publications

(31 citation statements)

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“…Although free fatty acids are generally kept at low micromolar concentrations in plasma (20), their concentration increases up to millimolar range in diabetic patients (29). Excessive influx of acetylCoA, both derived from glycolysis of glucose and ␤-oxidation of free fatty acids, in the tricarboxylic acid cycle can generate an accumulation of mitochondrial NADH in excess of electron transport capacity (3,21). This condition may lead to an overproduction of ROS at the mitochondrial level, which in turn stimulates NAD(P)H oxidase and other enzymes associated with amplification of oxidative stress and inflammation (15,26).…”

Section: Discussionmentioning

confidence: 99%

Laminar shear stress inhibits lipid peroxidation induced by high glucose plus arachidonic acid in endothelial cells

Mun¹,

An²,

Park³

et al. 2008

American Journal of Physiology-Heart and Circulatory Physiology

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Mun GI, An SM, Park H, Jo H, Boo YC. Laminar shear stress inhibits lipid peroxidation induced by high glucose plus arachidonic acid in endothelial cells. Am J Physiol Heart Circ Physiol 295: H1966-H1973, 2008. First published September 12, 2008 doi:10.1152/ajpheart.00727.2008.-Elevated blood glucose and free fatty acids induce oxidative stress associated with the incidence of cardiovascular disease. In contrast, laminar shear stress (LSS) plays a critical role in maintaining vascular health. The present study examined the mechanism for the antioxidant effect of LSS attenuating the oxidative stress induced by high glucose (HG) and arachidonic acid (AA) in human umbilical vein endothelial cells. HG and AA synergistically decreased cell viability and increased glutathione (GSH) oxidation and lipid peroxidation. The lipid peroxidation was markedly prevented by LSS as well as tetrahydrobiopterin (BH4) and GSH. LSS increased BH4 and GSH contents, and expression of GTP cyclohydrolase-1 and glutamylcysteine ligase (GCL) involved in their biosynthesis. Inhibition of GCL activity by DL-buthionine-(S,R)-sulfoximine and small-interfering RNA-mediated knockdown of GCL lessened the antioxidant effect of LSS. Therefore, it is suggested that LSS enhances antioxidant capacity of endothelial cells and thereby attenuates the oxidative stress caused by cardiovascular risk factors. laminar shear stress; high glucose; arachidonic acid; lipid peroxidation; glutamylcysteine ligase SHEAR STRESS, A HEMODYNAMIC force generated by blood flow, is known to regulate various vascular functions as well as gene expression in a magnitude-and flow pattern-dependent manner (22). The regions of arteries experiencing laminar shear stress (LSS) due to orderly blood flow are usually protected from atherosclerotic lesion formation, and thus LSS of relatively high level has been proposed to play anti-atherogenic roles. Differently from oscillatory shear stress, LSS usually does not stimulate inflammatory reactions but suppresses them probably by increasing nitric oxide (NO) production rather than reactive oxygen species (ROS) (8) or by induction of enzymes associated with antioxidant defense (25).Chronic LSS enhances endothelial NO production by inducing endothelial nitric oxide synthase (eNOS) expression (5). A recent study demonstrated that LSS increases the content of tetrahydrobiopterin (BH 4 ), an essential cofactor of eNOS, by activating GTP cyclohydrolase-1 (GTPCH-1), a rate-limiting enzyme for de novo synthesis of this cofactor, providing an additional mechanism for the increased NO production by LSS (34). However, BH 4 is very prone to oxidation by ROS and can be depleted under oxidative stress conditions. Then, eNOS reaction can be "uncoupled" and produce ROS instead of NO, causing further increase of oxidative stress, rather than attenuation of oxidative stress.Plasma free fatty acids are elevated in diabetic patients and play a role in the pathogenesis of diabetic vascular complications (35). High blood glucose and free fatty acids can cause...

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Section: Discussionmentioning

confidence: 99%

Laminar shear stress inhibits lipid peroxidation induced by high glucose plus arachidonic acid in endothelial cells

Mun¹,

An²,

Park³

et al. 2008

American Journal of Physiology-Heart and Circulatory Physiology

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“…It has been suggested that insulin resistance may be a response to protect the cell against damage caused by an increased activities of ROS by limiting nutrient entry into the cell (Fridlyand and Philipson 2006). It has also been reported that once insulin resistance is established in skeletal muscle, this may lead to a vicious cycle of increased blood glucose levels resulting in further oxidative stress and ineffective increases in circulating insulin concentration propagating the catabolic effects on the muscle (Leverve 2003).…”

mentioning

confidence: 99%

Absence of insulin signalling in skeletal muscle is associated with reduced muscle mass and function: evidence for decreased protein synthesis and not increased degradation

O’Neill

Wilding

Kahn

et al. 2010

AGE

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Loss of skeletal muscle mass and function is observed in many insulin-resistant disease states such as diabetes, cancer cachexia, renal failure and ageing although the mechanisms for this remain unclear. We hypothesised that impaired insulin signalling results in reduced muscle mass and function and that this decrease in muscle mass and function is due to both increased production of atrogenes and aberrant reactive oxygen species (ROS) generation. Maximum tetanic force of the extensor digitorum longus of muscle insulin receptor knockout (MIRKO) and lox/lox control mice was measured in situ. Muscles were removed for the measurement of mass, histological examination and ROS production. Activation of insulin signalling pathways, markers of muscle atrophy and indices of protein synthesis were determined in a separate group of MIRKO and lox/lox mice 15 min following treatment with insulin. Muscles from MIRKO mice had 36% lower maximum tetanic force generation compared with muscles of lox/lox mice. Muscle fibres of MIRKO mice were significantly smaller than those of lox/lox mice with no apparent structural abnormalities. Muscles from MIRKO mice demonstrated absent phosphorylation of AKT in response to exogenous insulin along with a failure to phosphorylate ribosomal S6 compared with lox/lox mice. Atrogin-1 and MuRF1 relative mRNA expression in muscles from MIRKO mice were decreased compared with muscles from lox/ lox mice following insulin treatment. There were no differences in markers of reactive oxygen species damage between muscles from MIRKO mice and lox/lox mice. These data support the hypothesis that the absence of insulin signalling contributes to reduced muscle mass and function though decreased protein synthesis rather than proteasomal atrophic pathways.

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“…The source of reduced NADP within the cell is the pentose phosphate shuttle, an alternate metabolic pathway of glucose sharing its first step with glycolysis 9 . The next step of the pentose phosphate shuttle is catalysed by specific enzyme glucose-6-phosphodehydrogenase which is notably inhibited by high glucose concentrations 10 . This is why high concentrations of glucose lead to increased glycolysis, mitochondrial metabolic activity and subsequently ROS production but at the same time they block production of NADP, thus attenuating the antioxidant protection of the cell.…”

Section: Discussionmentioning

confidence: 99%

High Glucose Increases Susceptibility to Oxidative-Stress-Induced Apoptosis and Dna Damage in K-562 Cells

Hruda¹,

Šrámek²,

Leverve³

2010

Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub

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glucose increases susceptibility to oxidative-stressinduced apoptosis and DNA damage in K-562 cells.. Biomedical papers of the Medical Faculty of the University Palacký, Olomouc, Czechoslovakia, 2010, 154 (4), pp.315-20. 315 Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub. 2010 154(4):315-320. © J. Hruda, V. Sramek, X Methods. Glucose at 5, 11 and 30 mM concentrations was tested, as well as 5 mM glutamine and 5 mM fructose. The cells were exposed to tert-butylhydroperoxide (tBH) and apoptotic cells were evaluated by flow cytometry with FITC-Annexin V and propidium iodide. The effect of glucose concentration on DNA damage was evaluated using hydrogen peroxide and electrophoretic "DNA comets" assay at 5 mM and 30 mM glucose concentrations.Results. The exposure of cells to tBH resulted in increased number of apoptotic cells, and this effect was prevented by administration of an antioxidant -N-Acetyl cysteine. Rising concentrations of glucose added to the toxic effect of tBH; we also observed some toxic effect of fructose and no effect of glutamine. We found higher susceptibility to hydrogen peroxide induced DNA damage with 30 mM glucose concentration.Conclusion. Hyperglycemia increases the cell's susceptibility to oxidative stress and it also amplifies oxidative DNA damage. Glutamine -when used as a sole energetic substrate -showed no protective effect against oxidative stress.

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Hyperglycemia and oxidative stress: complex relationships with attractive prospects

Cited by 46 publications

References 32 publications

Laminar shear stress inhibits lipid peroxidation induced by high glucose plus arachidonic acid in endothelial cells

Laminar shear stress inhibits lipid peroxidation induced by high glucose plus arachidonic acid in endothelial cells

Absence of insulin signalling in skeletal muscle is associated with reduced muscle mass and function: evidence for decreased protein synthesis and not increased degradation

High Glucose Increases Susceptibility to Oxidative-Stress-Induced Apoptosis and Dna Damage in K-562 Cells

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