Influence of diabetes on cardiac nitric oxide synthase expression and activity

Stockklauser-Färber, K.; Ballhausen, Th.; Laufer, A; Rösen, P.

doi:10.1016/s0925-4439(00)00078-8

Cited by 73 publications

(68 citation statements)

References 36 publications

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“…Stockklauser-Färber et al (2000) observed that the activity of total NOS and mRNA were dependent on the duration of diabetes in rat hearts, in which there was an increase in activity after 4-6 weeks, but a reduction after 20 weeks. It is now apparent that the mechanisms by which glucose may influence iNOS regulation may be cell-typedependent.…”

Section: Discussionmentioning

confidence: 96%

High glucose decreases intracellular glutathione concentrations and upregulates inducible nitric oxide synthase gene expression in intestinal epithelial cells

Powell¹,

Warpeha²,

Xu³

et al. 2004

Journal of Molecular Endocrinology

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Diabetes is associated with oxidative stress and increased concentrations of inflammatory cytokines. The aim of the study was to assess the effects of inflammatory cytokines and oxidative stress associated with increased glucose concentrations on inducible nitric oxide synthase (iNOS) promoter activity in intestinal epithelial cells. High-glucose (25 mmol/l) conditions reduced glutathione (GSH) concentrations in the human intestinal epithelial cell line, DLD-1. Addition of the antioxidant, α-lipoic acid, resulted in the restoration of GSH concentrations to normal. Upregulation of basal iNOS promoter activity was observed when cells were incubated in high glucose alone. This effect was significantly reduced by the addition of the antioxidant, α-lipoic acid, and completely blocked with inhibition of nuclear factor kappa B (NFκB) activity. Stimulation of cytokines (interleukin-1 beta, tumour necrosis factor-alpha, interferon-gamma) induced iNOS promoter activity in all conditions and this was accompanied by an increase in nitric oxide (NO) production. Inhibition of NFκB activity decreased, but did not completely inhibit, cytokine-induced iNOS promoter activity and subsequent production of NO. In conclusion, iNOS promoter activity induced by high concentrations of glucose is mediated in part through intracellular GSH and NFκB.

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Section: Discussionmentioning

confidence: 96%

High glucose decreases intracellular glutathione concentrations and upregulates inducible nitric oxide synthase gene expression in intestinal epithelial cells

Powell¹,

Warpeha²,

Xu³

et al. 2004

Journal of Molecular Endocrinology

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“…Recent evidence from our laboratory revealed that gene delivery of eNOS into cardiomyocytes directly improved cardiac contractile function through a phosphatidylinositol-3-kinase-dependent mechanism [35]. Additional evidence suggested that impairment of endothelium-dependent vasodilatation is not a direct consequence of reduced activity/expression of eNOS, but is rather triggered by an enhanced inactivation of nitric oxide by oxidative stress, especially ROS [38]. Oxidative stress and impaired cardiac contractile function have been demonstrated in insulin-resistant states such as type 2 diabetes, hypertension and obesity [1,39].…”

Section: Discussionmentioning

confidence: 97%

Cardiac overexpression of catalase rescues cardiac contractile dysfunction induced by insulin resistance: role of oxidative stress, protein carbonyl formation and insulin sensitivity

et al. 2006

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Aims/hypothesis: Insulin resistance leads to oxidative stress and cardiac dysfunction. This study examined the impact of catalase on insulin-resistanceinduced cardiac dysfunction, oxidative damage and insulin sensitivity. Methods: Insulin resistance was initiated in FVB and catalase-transgenic mice by 12 weeks of sucrose feeding. Contractile and intracellular Ca 2+ properties were evaluated in cardiomyocytes including peak shortening (PS), time-to-PS (TPS), time-to-90% relengthening (TR 90 ), half-width duration (HWD), maximal velocity of shortening/relengthening (±dL/dt), fura-fluorescence intensity change (ΔFFI) and intracellular Ca 2+ clearance rate (τ). Reactive oxygen species (ROS) and protein damage were evaluated with dichlorodihydrofluorescein and protein carbonyl formation. Results: Sucrose-fed mice displayed hyperinsulinaemia, impaired glucose tolerance and normal body weight. Myocytes from FVB sucrose-fed mice exhibited depressed PS and ±dL/dt, prolonged TR 90 and τ, and reduced ΔFFI associated with normal TPS and HWD compared with those from starch-fed control mice. ROS and protein carbonyl formation were elevated in FVB sucrose-fed mice. Insulin sensitivity was reduced, evidenced by impaired insulin-stimulated 2-deoxy-D-[ 3 H] glucose uptake. Western blot analysis indicated that sucrose feeding: (1) inhibited insulin-stimulated phosphorylation of insulin receptor and Akt; (2) enhanced proteintyrosine phosphatase 1B (PTP1B) expression; and (3) suppressed endothelial nitric oxide synthase (eNOS) and Na + -Ca 2+ exchanger expression without affecting peroxisome proliferator-activated receptor γ (PPARγ), sarco(endo)plasmic reticulum Ca 2+ -ATPase isozyme 2a and phospholamban. Catalase ablated insulin-resistanceinduced mechanical dysfunction, ROS production and protein damage, and reduced eNOS, but not insulin insensitivity. Catalase itself decreased resting FFI and enhanced expression of PTP1B and PPARγ. Conclusions/ interpretation: These data indicate that catalase rescues insulin-resistance-induced cardiac dysfunction related to ROS production and protein oxidation but probably does not improve insulin sensitivity.

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“…iNOS is predominantly expressed in inflammatory cells such as macrophages, although epithelial cells from affected tissues also express the enzyme. Intensified expression of iNOS has been detected in virtually all cell types tested, including macrophages, fibroblasts, chondrocytes, osteoclasts, and epithelial cells, and results in the production of much NO in animals and patients with inflammatory diseases (18)(19)(20)(21). The level of iNOS expression is well correlated with the degree of inflammation.…”

Section: Nitrooxidative Stress: a Possible Explanation Of The Controvmentioning

confidence: 99%

Melatonin: An Established Antioxidant Worthy of Use in Clinical Trials

Korkmaz

Reíter

Topal

et al. 2009

Mol Med

258

181

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Oxidative stress plays a key role in the pathogenesis of aging and many metabolic diseases; therefore, an effective antioxidant therapy would be of great importance in these circumstances. Nutritional, environmental, and chemical factors can induce the overproduction of the superoxide anion radical in both the cytosol and mitochondria. This is the first and key event that leads to the activation of pathways involved in the development of several metabolic diseases that are related to oxidative stress. As oxidation of essential molecules continues, it turns to nitrooxidative stress because of the involvement of nitric oxide in pathogenic processes. Once peroxynitrite forms, it damages via two distinctive mechanisms. First, it has direct toxic effects leading to lipid peroxidation, protein oxidation, and DNA damage. This mechanism involves the induction of several transcription factors leading to cytokine-induced chronic inflammation. Classic antioxidants, including vitamins A, C, and E, have often failed to exhibit beneficial effects in metabolic diseases and aging. Melatonin is a multifunctional indolamine that counteracts virtually all pathophysiologic steps and displays significant beneficial actions against peroxynitrite-induced cellular toxicity. This protection is related to melatonin′s antioxidative and antiinflammatory properties. Melatonin has the capability of scavenging both oxygen-and nitrogenbased reactants, including those formed from peroxynitrite, and blocking transcriptional factors, which induce proinflammatory cytokines. Accumulating evidence suggests that this nontoxic indolamine may be useful either as a sole treatment or in conjunction with other treatments for inhibiting the biohazardous actions of nitrooxidative stress.

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Influence of diabetes on cardiac nitric oxide synthase expression and activity

Cited by 73 publications

References 36 publications

High glucose decreases intracellular glutathione concentrations and upregulates inducible nitric oxide synthase gene expression in intestinal epithelial cells

High glucose decreases intracellular glutathione concentrations and upregulates inducible nitric oxide synthase gene expression in intestinal epithelial cells

Cardiac overexpression of catalase rescues cardiac contractile dysfunction induced by insulin resistance: role of oxidative stress, protein carbonyl formation and insulin sensitivity

Melatonin: An Established Antioxidant Worthy of Use in Clinical Trials

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