Regulation of Cerebral Vascular Function by Sirtuin 1

Tajbakhsh, Negara; Sokoya, Elke M.

doi:10.1111/j.1549-8719.2012.00167.x

Cited by 23 publications

(17 citation statements)

References 31 publications

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“…Recent investigations in rodent aortic and human endothelial cells reported the relevance of SIRT1 in eNOS activation; SIRT1 interacts with eNOS, resulting in the activation of the enzyme . In our study, SIRT1 up‐regulation during PC was well correlated with the expression of eNOS which was inhibited after sirtinol or EX527 administration.…”

Section: Discussionsupporting

confidence: 66%

Silent information regulator 1 protects the liver against ischemia-reperfusion injury: implications in steatotic liver ischemic preconditioning

et al. 2014

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Section: Discussionsupporting

confidence: 66%

Silent information regulator 1 protects the liver against ischemia-reperfusion injury: implications in steatotic liver ischemic preconditioning

et al. 2014

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“…2011), and others have documented the importance of SIRT-1 expression related to endothelial function in healthy arteries (Mattagajasingh et al . 2007; Tajbakhsh & Sokoya 2012). In an earlier study, we demonstrated that short-term CR could restore arterial SIRT-1 protein concentrations in old mice (Rippe et al .…”

Section: Discussionmentioning

confidence: 99%

Life-long caloric restriction reduces oxidative stress and preserves nitric oxide bioavailability and function in arteries of old mice

et al. 2013

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Aging impairs arterial function through oxidative stress and diminished nitric oxide (NO) bioavailability. Life-long caloric restriction (CR) reduces oxidative stress, but its impact on arterial aging is incompletely understood. We tested the hypothesis that life-long CR attenuates key features of arterial aging. Blood pressure, pulse wave velocity (PWV) (arterial stiffness), carotid artery wall thickness and endothelium-dependent dilation (EDD) (endothelial function) were assessed in young (Y: 5–7 mo), old ad libitum (Old AL: 30–31 mo.) and life-long 40% CR old (30–31 mo.) B6D2F1 mice. Blood pressure was elevated with aging (P<0.05) and was blunted by CR (P<0.05 vs. Old AL). PWV was 27% greater in old vs. young AL fed mice (P<0.05), and CR prevented this increase (P<0.05 vs. Old AL). Carotid wall thickness was greater with age (P<0.05), and CR reduced this by 30%. CR effects were associated with amelioration of age-related changes in aortic collagen and elastin. Nitrotyrosine, a marker of cellular oxidative stress, and superoxide production was greater in old AL vs. young (P<0.05) and CR attenuated this increase. Carotid artery EDD was impaired with age (P<0.05); CR prevented this by enhancing NO and reducing superoxide-dependent suppression of EDD (Both P<0.05 vs. Old AL). This was associated with a smaller age-related increase in NADPH oxidase activity and p67 expression, with increases in superoxide dismutase (SOD), total SOD and catalase activities (All P<0.05 Old CR vs. Old AL). Lastly, CR normalized age-related changes in the critical nutrient sensing pathways SIRT-1 and mTOR (P<0.05 vs. Old AL). Our findings demonstrate that CR is an effective strategy for attenuation of arterial aging.

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“…Hyperglycemia decreases SIRT1 expression in cultured endothelial cells [4], whereas overexpression of SIRT1 prevents the hyperglycemia-induced vascular cell senescence and thereby protects against vascular dysfunction in mice with diabetes [4], [5]. SIRT1 is expressed not only in the endothelium but also in VSMCs [2], [6], [7], where it is required for both growth and proliferation, suggesting a potential role of SIRT1 in the control of vascular function under various stress stimuli.…”

Section: Introductionmentioning

confidence: 99%

Regulation of SIRT1 in Vascular Smooth Muscle Cells from Streptozotocin-Diabetic Rats

et al. 2013

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Sirtuins enzymes are a conserved family of nicotinamide adenine dinucleotide (NAD)-dependent deacetylases and ADP-ribosyltransferases that mediate responses to oxidative stress, fasting and dietary restriction in mammals. Vascular smooth muscle cells (VSMCs) are involved in many mechanisms that regulate vascular biology in vivo but the role of SIRT1 has not been explored in much detail. Therefore, we investigated the regulation of SIRT1 in cultured VSMCs under various stress conditions including diabetes. Sprague-Dawley rats were made diabetic by injecting a single dose of streptozotocin (65 mg/Kg), and aortic VSMCs were isolated after 4 weeks. Immunocytochemistry showed that SIRT1 was localized predominantly in the nucleus, with lower staining in VSMCs from STZ-diabetic as compared with normoglycemic rats. Previous diabetes induction in vivo and high glucose concentrations in vitro significantly downregulated SIRT1 amounts as detected in Western blot assays, whereas TNF-α (30 ng/ml) stimulation failed to induce significant changes. Because estrogen signaling affects several pathways of oxidative stress control, we also investigated SIRT1 modulation by 17β-estradiol. Treatment with the hormone (10 nM) or a selective estrogen receptor-α agonist decreased SIRT1 levels in VSMCs from normoglycemic but not in those from STZ-diabetic animals. 17β-estradiol treatment also enhanced activation of AMP-dependent kinase, which partners with SIRT1 in a signaling axis. SIRT1 downregulation by 17β-estradiol could be observed as well in human peripheral blood mononuclear cells, a cell type in which SIRT1 downregulation is associated with insulin resistance and subclinical atherosclerosis. These data suggest that SIRT1 protein levels are regulated by diverse cellular stressors to a variable extent in VSMCs from diabetic and normoglycemic rats, warranting further investigation on SIRT1 as a modulator of VSMC activity in settings of vascular inflammation.

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Regulation of Cerebral Vascular Function by Sirtuin 1

Abstract: Our results support a role for SIRT1 in endothelium-dependent relaxation in the cerebral vasculature and reveal a potential for SIRT1 as a therapeutic target in vascular-related diseases by restoring endothelial function.

Cited by 23 publications

References 31 publications

Silent information regulator 1 protects the liver against ischemia-reperfusion injury: implications in steatotic liver ischemic preconditioning

Silent information regulator 1 protects the liver against ischemia-reperfusion injury: implications in steatotic liver ischemic preconditioning

Life-long caloric restriction reduces oxidative stress and preserves nitric oxide bioavailability and function in arteries of old mice

Regulation of SIRT1 in Vascular Smooth Muscle Cells from Streptozotocin-Diabetic Rats

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