Regulation of Inducible Nitric Oxide Synthase (iNOS) and its Potential Role in Insulin Resistance, Diabetes and Heart Failure

Šoškić, Sanja; Dobutović, Branislava; Sudar-Milovanović, Emina; Obradović, Milan; Nikolić, Dragana; Djordjević, Jelena; Radak, Djordje; Mikhailidis, Dimitri P.; Isenović, Esma R.

doi:10.2174/1874192401105010153

Cited by 134 publications

(96 citation statements)

References 176 publications

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“…These complications lead to increased morbidity and mortality rate among these patients [1]. Nitric oxide (NO) is a gaseous free radical that is generated under the influence of nitric oxide synthase (NOS) and has been proven to plays an integral role in several physiological activities in cell-cell communication, cellular defense, and cell injury [17] as well as being an intermediate in the pathology of several systemic diseases including cardiovascular diseases and both types of diabetes mellitus [18].…”

Section: Discussionmentioning

confidence: 99%

Effect of Exercise Training on the Expression of p53 and iNOS in the Cardiac Muscle of Type I Diabetic Rats

Al-Jarrah

2012

J Endocrinol Metab

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Background: Diabetes is associated with a marked increase in the risk of cardiac diseases, including atherosclerosis, cardiomyopathy, and impaired ventricular function. The ability of exercise to reduce the risk of cardiac troubles has been established, but no studies have examined this link in type 1 diabetes. A randomized, controlled animal study was designed using a standard rat model of type 1 diabetes. The goal of this study was to investigate the expression of P53 and iNOS in cardiac muscle of rat with Alloxan-induced diabetes.

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Section: Discussionmentioning

confidence: 99%

Effect of Exercise Training on the Expression of p53 and iNOS in the Cardiac Muscle of Type I Diabetic Rats

Al-Jarrah

2012

J Endocrinol Metab

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“…The enhanced oxidative stress in diabetes promotes iNOS up-regulation, BH4 oxidation, and, consequently, iNOS uncoupling, thus further exacerbating the oxidative/nitrosative stress (186,251). However, Okazaki et al showed that BH4 treatment was sufficient to restore iNOS coupling in isolated diabetic rat hearts and the iNOSderived NO conferred cardioprotection against I/R injury in terms of both infarct size and left ventricular function (21,83,112,195).…”

Section: Ischemia/reperfusion Injury and Infarctionmentioning

confidence: 99%

Tetrahydrobiopterin in Cardiovascular Health and Disease

Bendall

Douglas

McNeill

et al. 2014

Antioxidants & Redox Signaling

192

187

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Tetrahydrobiopterin (BH4) functions as a cofactor for several important enzyme systems, and considerable evidence implicates BH4 as a key regulator of endothelial nitric oxide synthase (eNOS) in the setting of cardiovascular health and disease. BH4 bioavailability is determined by a balance of enzymatic de novo synthesis and recycling, versus degradation in the setting of oxidative stress. Augmenting vascular BH4 levels by pharmacological supplementation has been shown in experimental studies to enhance NO bioavailability. However, it has become more apparent that the role of BH4 in other enzymatic pathways, including other NOS isoforms and the aromatic amino acid hydroxylases, may have a bearing on important aspects of vascular homeostasis, inflammation, and cardiac function. This article reviews the role of BH4 in cardiovascular development and homeostasis, as well as in pathophysiological processes such as endothelial and vascular dysfunction, atherosclerosis, inflammation, and cardiac hypertrophy. We discuss the therapeutic potential of BH4 in cardiovascular disease states and attempt to address how this modulator of intracellular NO-redox balance may ultimately provide a powerful new treatment for many cardiovascular diseases. Antioxid. Redox Signal. 20, 3040-3077.

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“…A previous study has dem- onstrated that H 2 O 2 could activate the NF-κB pathway in hLEC [30], whereas inactivation of NF-κB pathway effectively alleviated the cytotoxicity of H 2 O 2 to hLEC [21], and consistently, the NF-κB p65 translocated from the cytoplasm to the nucleus when NF-κB pathway was activated in cataract [31]. The possible reason might be that NF-κB could act as a pro-oxidant gene to increase the binding with iNOS promoter to enhance the expression of iNOS [32], which is a crucial enzyme related to oxidative stress to promote the excessive production of nitric oxide and superoxide anions (O 2 -), resulting in extensive oxidative damage [33]. However, no significant difference was discovered between the H 2 O 2 group and the inhibitors + PDTC + H 2 O 2 group concerning the oxidative stress-related indices, suggesting that miRNA-124 may directly affect NF-κB p65 [17] to inhibit the oxidative stress of hLEC induced by H 2 O 2 .…”

Section: Discussionmentioning

confidence: 99%

MicroRNA-124 Prevents H<sub>2</sub>O<sub>2</sub>-Induced Apoptosis and Oxidative Stress in Human Lens Epithelial Cells via Inhibition of the NF-κB Signaling Pathway

Gu¹

2018

Pharmacology

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Aim: To investigate the regulation of microRNA-124 (miRNA-124) on NF-κB pathway from H₂O₂-induced apoptosis and oxidative stress in human lens epithelial cells (hLEC). Methods: The MTT (3-[4, 5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide) assay was used to detect hLEC viability. HLECs were divided into Blank, H₂O₂, mimics (miRNA-124 mimics) + H₂O₂, NC+ H₂O₂, pyrrolidine dithiocarbamate (PDTC; NF-κB signaling pathway inhibitor) + H₂O₂, and inhibitors (miRNA-124 inhibitors) + PDTC + H₂O₂ groups. Quantitative real-time polymerase chain reaction and Western blot were employed to detect mRNA and protein expressions, Dichloro-dihydro-fluorescein diacetate to measure reactive oxygen species (ROS) production, and AnnexinV-FITC/PI staining to determine cell apoptosis. The mitochondrial membrane potential (MMP) was detected by fluorescence probe JC-1. Results: The H₂O₂-induced hLEC showed reductions in cell viability with decreased miRNA-124 but increased p-p65 in a dose-/time-dependent manner. Furthermore, ROS production, malondialdehyde content, Bax and Caspase-3 expressions, and cell apoptosis were elevated in H₂O_2-induced hLEC, whereas the activities of superoxide dismutase and glutathione peroxidase, Bcl-2 expression, MMP, as well as the mitochondrial energy metabolism genes were reduced. Additionally, miRNA-124 mimics and PDTC both decreased the p-p65 and reversed the cytotoxicity in H₂O₂-induced hLEC. Conclusion: MiRNA-124 prevents H₂O₂-induced oxidative stress and apoptosis in hLEC through suppressing the activation of the NF-κB pathway.

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Regulation of Inducible Nitric Oxide Synthase (iNOS) and its Potential Role in Insulin Resistance, Diabetes and Heart Failure

Cited by 134 publications

References 176 publications

Effect of Exercise Training on the Expression of p53 and iNOS in the Cardiac Muscle of Type I Diabetic Rats

Effect of Exercise Training on the Expression of p53 and iNOS in the Cardiac Muscle of Type I Diabetic Rats

Tetrahydrobiopterin in Cardiovascular Health and Disease

MicroRNA-124 Prevents H<sub>2</sub>O<sub>2</sub>-Induced Apoptosis and Oxidative Stress in Human Lens Epithelial Cells via Inhibition of the NF-κB Signaling Pathway

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