Repression of P66Shc Expression by SIRT1 Contributes to the Prevention of Hyperglycemia-Induced Endothelial Dysfunction

Zhou, Shuang; Chen, Hou-Zao; Wan, Yong; Zhang, Qingjun; Wei, Yu‐Sheng; Huang, Shuai; Liu, Jinjing; Lu, Yunbiao; Zhang, Zhu-Qin; Yang, Ruifeng; Zhang, Ran; Cai, Hua; Liu, Depei; Liang, Chih‐Chuan

doi:10.1161/circresaha.111.243592

Cited by 246 publications

(237 citation statements)

References 37 publications

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“…Mechanistically, SIRT1 binds to PPAR␣, favoring the deacetylation of PPAR␥ coactivator 1␣ and preventing the down-regulation of fatty acid oxidation genes (75). In line with a protective role for SIRT1 in cardiovascular disease, it also protects mice from hyperglycemia-induced endothelial dysfunction by inhibiting the expression of p66Shc (77). Mice deficient in p66Shc have increased resistance to oxidative stress and improved endothelial function and are protected against vascular and cardiac diseases (78).…”

Section: Cardiovascular Diseasementioning

confidence: 96%

From Sirtuin Biology to Human Diseases: An Update

Sebastián

Satterstrom

Haigis

et al. 2012

Journal of Biological Chemistry

210

159

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Originally rising to notoriety for their role in the regulation of aging, sirtuins are a family of NAD ؉ -dependent enzymes that have been connected to a steadily growing set of biological processes. In addition to regulating aging, sirtuins play key roles in the maintenance of organismal metabolic homeostasis. These enzymes also have primarily protective functions in the development of many age-related diseases, including cancer, neurodegeneration, and cardiovascular disease. In this minireview, we provide an update on the known roles for each of the seven mammalian sirtuins in these areas.Over three-quarters of a century ago, Clive McCay and colleagues first noted that rats kept on a calorie-restricted diet lived longer than freely fed controls (1). Despite the length of time that has elapsed since this discovery, the molecular mechanism that drives this life span extension has remained elusive. Originally described as a silencing factor in yeast (silencing information regulator), the protein Sir2 came out on top in a screen for modulators of yeast life span (2). Moreover, Sir2 was required for the life span of yeast to be extended by calorie restriction (3). These discoveries launched a new field in biology: the study of Sir2 and its homologs in mammals, called sirtuins.Mammals have seven sirtuins (SIRT1-7) that possess NAD ϩ -dependent deacetylase, deacylase, and ADP-ribosyltransferase activities (4). Sirtuins are found in different subcellular locations, including the nucleus (SIRT1, SIRT6, and SIRT7), cytosol (SIRT2), and mitochondria (SIRT3-5), although in some studies, SIRT1 has been found to possess cytosolic activities, and SIRT2 has been found to associate with nuclear proteins. Sirtuins have important functions in a diverse yet interrelated set of physiological processes. In this minireview, we discuss research done in the past four years featuring their roles in aging, metabolism, cancer biology, cardiovascular disease, inflammation, and brain pathology. AgingFollowing the first publication describing a role for yeast Sir2 in promoting longevity (2), many laboratories focused on elucidating whether sirtuins might play similar roles in other organisms. Sirtuins have been shown to regulate life span in lower organisms, including yeast, nematodes, and fruit flies (5), although their role in worm and fly life span has recently been debated (6, 7). Most of these studies have described a key role for SIRT1 in regulating the metabolic response to calorie restriction (CR) 5 (8), a dietary intervention that robustly extends life span across numerous species. However, wholebody overexpression of SIRT1 in mice does not affect life span (9). Nevertheless, SIRT1 does appear to promote healthy aging by protecting against several age-related pathologies (10).The strongest link between mammalian sirtuins and the antiaging effects of CR comes from SIRT3, which mediates the prevention of age-related hearing loss by CR (11). Hearing loss is a hallmark of mammalian aging and is characterized by a gradual loss of spiral...

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Section: Cardiovascular Diseasementioning

confidence: 96%

From Sirtuin Biology to Human Diseases: An Update

Sebastián

Satterstrom

Haigis

et al. 2012

Journal of Biological Chemistry

210

159

View full text Add to dashboard Cite

show abstract

“…The homogenates were sonicated and centrifuged at 4°C for 15 min, and the supernatants were used for western blotting. The western blot was performed as described previously (Zhou et al, 2011). The primary antibodies were used for PON1 (Abcam, ab24261), PON2 (Epitomics, S1585), PON3 (Abcam, ab42322), MMP2 (Epitomics, 2008-1), MMP9 (CST, 2270), TIMP1 (Santa, sc-5538), TIMP2 (Abcam, ab1828), GAPDH (Abcam, ab8245).…”

Section: Western Blot Analysismentioning

confidence: 99%

Human paraoxonase gene cluster overexpression alleviates angiotensin II-induced cardiac hypertrophy in mice

Pei

Yan

Tang

et al. 2016

Sci. China Life Sci.

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Cardiac hypertrophy is the strongest predictor of the development of heart failure, and anti-hypertrophic treatment holds the key to improving the clinical syndrome and increasing the survival rates for heart failure. The paraoxonase (PON) gene cluster (PC) protects against atherosclerosis and coronary artery diseases. However, the role of PC in the heart is largely unknown. To evaluate the roles of PC in cardiac hypertrophy, transgenic mice carrying the intact human PON1, PON2, and PON3 genes and their flanking sequences were studied. We demonstrated that the PC transgene (PC-Tg) protected mice from cardiac hypertrophy induced by Ang II; these mice had reduced heart weight/body weight ratios, decreased left ventricular wall thicknesses and increased fractional shortening compared with wild-type (WT) control. The same protective tendency was also observed with an Apoe / background. Mechanically, PC-Tg normalized the disequilibrium of matrix metalloproteinases (MMPs)/tissue inhibitors of MMPs (TIMPs) in hypertrophic hearts, which might contribute to the protective role of PC-Tg in cardiac fibrosis and, thus, protect against cardiac remodeling. Taken together, our results identify a novel anti-hypertrophic role for the PON gene cluster, suggesting a possible strategy for the treatment of cardiac hypertrophy through elevating the levels of the PON gene family.cardiac hypertrophy, fibrosis, paraoxonase gene cluster, angiotensin II Citation:

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“…Chromatin immunoprecipitation (ChIP) assays were performed in HUVECs as described [19]. A rabbit polyclonal antibody for SIRT1 (Santa Cruz Biotechnology, Cat #sc-15404) was used in ChIP assay.…”

Section: Chipmentioning

confidence: 99%

SIRT1 suppresses PMA and ionomycin-induced ICAM-1 expression in endothelial cells

Jia

Gao

Chen

et al. 2012

Sci. China Life Sci.

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Intercellular adhesion molecule-1 (ICAM-1) plays an important role in the recruitment of leukocytes to the endothelium, which causes inflammation and initiation of atherosclerosis. We have previously shown that endothelium-specific over-expression of class III deacetylase SIRT1 decreases atherosclerosis. We therefore addressed the hypothesis that SIRT1 suppresses ICAM-1 expression in the endothelial cells. Here, we found that expression of SIRT1 and ICAM-1 was significantly induced by PMA and ionomycin (PMA/Io) in human umbilical vein endothelial cells (HUVECs). Adenovirus-mediated over-expression of SIRT1 significantly inhibited PMA/Io-induced ICAM-1 expression in HUVECs. Knockdown of SIRT1 by RNA interference (RNAi) resulted in increased expression of ICAM-1 in HUVECs. Luciferase report assay showed that over-expression of SIRT1 suppressed ICAM-1 promoter activity both in basic and in PMA/Io-induced conditions. We further found that SIRT1 was involved in transcription complex binding on the ICAM-1 promoter by chromatin immunoprecipitation (ChIP) assays. Furthermore, SIRT1 RNAi increased NF-κB p65 binding ability to the ICAM-1 promoter by ChIP assays. Overall, these data suggests that SIRT1 inhibits ICAM-1 expression in endothelial cells, which may contribute to its anti-atherosclerosis effect. SIRT1, ICAM-1, PMA and ionomycin Citation:Jia Y Y, Gao P, Chen H Z, et al. SIRT1 suppresses PMA and ionomycin-induced ICAM-1 expression in endothelial cells .

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Repression of P66Shc Expression by SIRT1 Contributes to the Prevention of Hyperglycemia-Induced Endothelial Dysfunction

Cited by 246 publications

References 37 publications

From Sirtuin Biology to Human Diseases: An Update

From Sirtuin Biology to Human Diseases: An Update

Human paraoxonase gene cluster overexpression alleviates angiotensin II-induced cardiac hypertrophy in mice

SIRT1 suppresses PMA and ionomycin-induced ICAM-1 expression in endothelial cells

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