Angiotensin II-induced JNK activation is mediated by NAD(P)H oxidase in isolated rat pancreatic islets

Alves, Eduardo da Silva; Haidar, André Abou; Quadros, C. D.; Carvalho, Daniela; Morgan, D.; Rocha, M. S.; Curi, Rui; Carpinelli, Ângelo Rafael; Hirata, Aparecida Emiko

doi:10.1016/j.regpep.2012.01.003

Cited by 6 publications

(3 citation statements)

References 35 publications

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“…AT1r activation leads to the phosphorylation of tyrosine kinases, including JAK2 [29]. Recently, it was reported that in the liver, JAK2 phosphorylation is an important step in HSC activation [10].…”

Section: Discussionmentioning

confidence: 99%

Short-term administration of GW501516 improves inflammatory state in white adipose tissue and liver damage in high-fructose-fed mice through modulation of the renin-angiotensin system

et al. 2015

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High activation of the angiotensin-converting enzyme (ACE)/(angiotensin-II type 1 receptor) AT1r axis is closely linked to pro-inflammatory effects and liver damage. The aim of this study was to evaluate the effects of the short-term administration of GW501516 on pro-inflammatory markers in white adipose tissue (WAT) and hepatic stellate cells (HSCs), lipogenesis and insulin resistance in the liver upon high-fructose diet (HFru)-induced ACE/AT1r axis activation. Three-month-old male C57Bl/6 mice were fed a standard chow diet or a HFru for 8 weeks. Then, the animals were separated randomly into four groups and treated with GW501516 for 3 weeks. Morphological variables, systolic blood pressure, and plasma determinations were analyzed. In the WAT, the ACE/AT1r axis and pro-inflammatory cytokines were assessed, and in the liver, the ACE/AT1r axis, HSCs, fatty acid oxidation, insulin resistance, and AMPK activation were evaluated. The HFru group displayed a high activation of the ACE/AT1r axis in both the WAT and liver; consequently, we detected inflammation and liver damage. Although GW501516 abolished the increased activation of the ACE/AT1r axis in the WAT, no differences were found in the liver. GW501516 blunted the inflammatory state in the WAT and reduced HSC activation in the liver. In addition, GW501516 alleviates damage in the liver by increasing the expression of the genes that regulate beta-oxidation and decreasing the expression of the genes and proteins that are involved in lipogenesis and gluconeogenesis. We conclude that GW501516 may serve as a therapeutic option for the treatment of a highly activated ACE/AT1r axis in WAT and liver.

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Section: Discussionmentioning

confidence: 99%

Short-term administration of GW501516 improves inflammatory state in white adipose tissue and liver damage in high-fructose-fed mice through modulation of the renin-angiotensin system

et al. 2015

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“…Activation of JNK has been implicated in the cytotoxicity of AngII (Alves et al 2012). Importantly, activation of JNK has been reported to play an important role in the pathogenesis of cardiovascular and metabolic diseases (Zhou et al 2010).…”

Section: Discussionmentioning

confidence: 99%

Upregulation of sestrin-2 expression protects against endothelial toxicity of angiotensin II

Liu¹,

Li²,

Yuan³

et al. 2014

Cell Biol Toxicol

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Sestrin-2 (SESN2) is involved in the cellular response to different stress conditions. However, the function of SESN2 in the cardiovascular system remains unknown. In the present study, we tested whether SESN2 has a beneficial effect on vascular endothelial damage induced by angiotensin II (AngII). Firstly, we found that AngII induces expression of SESN2 in human umbilical vein endothelial cells (HUVECs) in a time-dependent and dose-dependent manner. We also found that knockdown of SESN2 using small RNA interference promotes cellular toxicity of AngII, as well as a reduction in cell viability, exacerbation of oxidative stress, and stimulation of apoptosis. In addition, our results show that the c-Jun NH (2)-terminal kinase (JNK)/c-Jun pathway is activated by AngII. Inhibiting the activity of the JNK pathway abolishes the increase in SESN2 induced by AngII. Importantly, overexpression of c-Jun promotes luciferase activity of the SESN2 promoter. These findings suggest that the inductive effect of SESN2 is mediated by the JNK/c-Jun pathway. Our results indicate that the induction of SESN2 acts as a compensatory response to AngII for survival, implying that stimulating expression of SESN2 might be an effective pharmacological target for the treatment of AngII-associated cardiovascular diseases.

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“…Ang II activates NOX‐4, increases production of superoxide, and activates MAPKs in rat pancreatic islets (Alves et al. ). However, Ang II levels were not different among groups on postop 6 month.…”

Section: Discussionmentioning

confidence: 99%

Oxidative stress increases the risk of pancreatic β cell damage in chronic renal hypertensive rats

et al. 2016

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Hypertension often occurs in conjunction with insulin resistance. The purpose of this study was to evaluate whether sustained renal hypertension increases the risk of diabetes mellitus in rats, and to define the underlying mechanisms. Two‐kidney, one‐clip hypertensive (2K1C) rats received captopril (50 mg/kg/day), α‐lipoic acid (100 mg/kg/day), or vehicle treatment for 3 months after surgery. Blood pressure was measured by tail cuff plethysmography. Oral glucose tolerance test (OGTT), immunohistochemistry, and western blotting were performed. In addition, insulin secretion from islet cells was measured. OGTT yielded abnormal results, and the number of islet cells and the size of pancreatic β/α cells were decreased in 2K1C rats. Basal insulin levels were also reduced in the plasma. Insulin secretion from pancreatic islet cells in response to high glucose was also attenuated in 2K1C rats compared with sham rats. The levels of oxidative stress markers, including 8‐hydroxydeoxyguanosine and NADPH oxidase‐4, were increased in pancreatic tissue and pancreatic islets in 2K1C rats. The abnormalities observed in 2K1C rats were improved by captopril or α‐lipoic acid treatment. These findings indicate that sustained renal hypertension may lead to pancreatic dysfunction, increasing oxidative stress in pancreatic islets.

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Angiotensin II-induced JNK activation is mediated by NAD(P)H oxidase in isolated rat pancreatic islets

Cited by 6 publications

References 35 publications

Short-term administration of GW501516 improves inflammatory state in white adipose tissue and liver damage in high-fructose-fed mice through modulation of the renin-angiotensin system

Short-term administration of GW501516 improves inflammatory state in white adipose tissue and liver damage in high-fructose-fed mice through modulation of the renin-angiotensin system

Upregulation of sestrin-2 expression protects against endothelial toxicity of angiotensin II

Oxidative stress increases the risk of pancreatic β cell damage in chronic renal hypertensive rats

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