Paeonol protects against premature senescence in endothelial cells by modulating Sirtuin 1 pathway

Jamal, Juliana; Mustafa, Mohd Rais; Wong, Pooi-Fong

doi:10.1016/j.jep.2014.04.025

Cited by 56 publications

(43 citation statements)

References 36 publications

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“…Indeed, several chemicals are reported to have anti-senescent effect in vitro by modulating SIRT1 pathway. These chemicals include a number of agents including resveratrol, 19) cilostazol, 41) paeonol, 43) statins, 21) hydrogen sulfide 23,44) and persimmon. 45) Yang et al 15) demonstrated that pretreatment with curcumin attenuated mitochondrial oxidative damage induced by myocardial ischemia reperfusion injury through activation of SIRT1.…”

Section: Discussionmentioning

confidence: 99%

Curcumin Attenuates Hydrogen Peroxide-Induced Premature Senescence <i>via</i> the Activation of SIRT1 in Human Umbilical Vein Endothelial Cells

Sun

et al. 2015

Biological & Pharmaceutical Bulletin

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Endothelial senescence has been proposed to be involved in endothelial dysfunction and atherogenesis. Curcumin, a natural phenol, possesses antioxidant and anti-inflammatory properties. However, the effect of curcumin on endothelial senescence is unclear. This study explores the effect of curcumin on hydrogen peroxide (H 2 O 2 )-induced endothelial premature senescence and the mechanisms involved. Human umbilical vein endothelial cells (HUVECs) were cultured, and premature senescence was induced with 100 µM H 2 O 2 . Results showed that pretreatment with curcumin significantly attenuated the H 2 O 2 -induced HUVECs' premature senescence, which was evidenced by a decreased percentage of senescence-associated β-galactosidase positive cells, improved cell division and decreased expression of senescence-associated protein p21 (all p<0.05). Pretreatment with curcumin decreased oxidative stress and apoptosis in H 2 O 2 -treated HUVECs. Treatment of HUVECs with H 2 O 2 also down-regulated the phosphorylation of endothelial nitric oxide synthase (eNOS), decreased the level of nitric oxide in the culture medium, and inhibited the protein expression and enzymatic activity of silent information regulator 1 (SIRT1), while pretreatment with curcumin partly reversed these effects (all p<0.05). Treatment with curcumin alone enhanced the enzymatic activity of SIRT1, but didn't affect cellular senescence, cell growth or apoptosis compared to the Control. The inhibition of SIRT1 using SIRT1 short interfering RNA (siRNA) could decrease the expression and phosphorylation of eNOS and abrogate the protective effect of curcumin on H 2 O 2 -induced premature senescence. These findings suggest that curcumin could attenuate oxidative stress-induced HUVECs' premature senescence via the activation of SIRT1.Key words curcumin; endothelial senescence; silent information regulator 1 (SIRT1); hydrogen peroxide Cellular senescence is defined as an irreversible state of growth arrest and accompanied by a specific set of phenotypic changes, gene expression and cell function.1) It has been realized that senescence is induced by a variety of insults, including those causing intracellular oxidative stress, such as hydrogen peroxide (H 2 O 2 ).2) This kind of cellular senescence is called the stress-induced premature senescence (SIPS). Endothelial senescence has been proposed to be involved in endothelial dysfunction and atherogenesis.3) Human studies showed that there were vascular cells exhibiting the morphological features of cellular senescence. [4][5][6] Silent information regulator 1 (SIRT1) is a member of the sirtuin family of proteins, which are homologs of the Sir2 gene in Saccharomyces (S.) cerevisiae. SIRT1 has been known as an oxidized form of nicotinamide adenine dinucleotide (NAD + )-dependent class III histone deacetylase (HDAC) and plays a key role in regulating cellular senescence, cell survival and metabolism through deacetylation of various histones and non-histone substrates.7,8) SIRT1 is highly expressed in the vasculature. A gro...

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Section: Discussionmentioning

confidence: 99%

Curcumin Attenuates Hydrogen Peroxide-Induced Premature Senescence <i>via</i> the Activation of SIRT1 in Human Umbilical Vein Endothelial Cells

Sun

et al. 2015

Biological & Pharmaceutical Bulletin

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“…Traditional Chinese medicine uses this compound alleviating various oxidative stress-related diseases. Jamal et al (15) suggest a beneficial role of paeonol on premature senescence in a SIRT1-dependent manner. However, the mechanism of action for this compound is still unknown.…”

Section: Discussionmentioning

confidence: 99%

“…Overexpression of endothelium-specific SIRT1 protects against endothelial dysfunction induced by a high-fat diet and hyperglycemia (12,13). Recently, resveratrol (RSV) and paeonol (2′-Hydroxy-4′-methoxyacetophenone) have been shown to activate SIRTs and thus can be used for pharmacological interventions (14,15). Activation of SIRT1 by RSV can improve vascular functions (16), while paeonol prevented premature senescence induced by oxidative stress in human umbilical vein endothelial cells (HUVECs) by modulating the expression of SIRT1 (15).…”

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confidence: 99%

Gestational diabetes induces alterations of sirtuins in fetal endothelial cells

et al. 2015

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Background: Gestational diabetes (GDM) has long-term consequences for the offspring. Sirtuins (SIRTs) are associated with vascular and metabolic functions. We studied the impact of GDM on SIRT activity and expression in fetal endothelial colony-forming cells (ECFCs) and human umbilical vein endothelial cells (HUVECs) from pregnancies complicated by GDM. Methods: ECFCs and HUVECs were isolated from cord and cord blood of 10 uncomplicated pregnancies (NPs) and 10 GDM pregnancies. Nicotinamidadenindinukleotid (NAD + ) concentration, SIRT1 and SIRT3 activity, transcription levels of SIRT1, SIRT3, and SIRT4, and protein levels of SIRT1, SIRT3, and SIRT4 were determined in vitro with or without SIRT activators resveratrol (RSV) and paeonol. results: Fetal ECFCs from GDM pregnancies showed a decreased NAD + concentration, reduced SIRT1 and SIRT3 activity, and lower transcription levels of SIRT1, SIRT3, and SIRT4. HUVECs from GDM pregnancies had decreased NAD + concentrations and transcription levels of SIRT1 and SIRT4. RSV markedly enhanced the expression and activity of SIRTs in ECFCs and HUVECs, while paeonol was active only in ECFCs. conclusion: A reduction of SIRT activity and expression in fetal endothelial cells provides potential mechanistic insights into the pathophysiology of long-term cardiovascular complications observed in the offspring of GDM pregnancies. SIRT activators can increase SIRT activity in ECFCs, which opens perspectives for new therapeutic targets. a dverse events during fetal life have been implicated to induce fetal programming, which can result in chronic diseases (1). Especially gestational diabetes (GDM) of the mother has been associated with cardiovascular disease, metabolic syndrome, and obesity during later life in the offspring (2,3). The pathophysiological processes responsible for these late complications are largely unknown.Sirtuins (SIRTs) are important regulators of aging and metabolic diseases (4,5). Mammalian SIRTs belong to the histone deacetylase class III family comprising seven members (SIRT1-7), which require Nicotinamidadenindinukleotid (NAD + ) for their enzymatic activity (6). SIRT1 downregulation has been observed in peripheral blood mononuclear cells of individuals with impaired glucose tolerance (7,8). SIRT1 is known to regulate vascular endothelial cell functions (9). Furthermore, in vitro and in vivo studies demonstrated that a reduction in the number of endothelial progenitor cells (EPCs) under hyperglycemia is associated with reduced SIRT1 levels and activity (8,10). Endothelial cells regulate vascular tone and are the first fetal cells exposed to maternal hyperglycemia.In recent years, it has become evident that SIRT1 is a key player of EPC dysfunction in insulin resistance and metabolic syndrome (7,10,11). Overexpression of endothelium-specific SIRT1 protects against endothelial dysfunction induced by a high-fat diet and hyperglycemia (12,13). Recently, resveratrol (RSV) and paeonol (2′-Hydroxy-4′-methoxyacetophenone) have been shown to activate SIRTs and thus c...

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“…The activity of SIRT1 has been shown to be rescued by several compounds, such as resveratrol (D'Onofrio et al 2015;Sanchez-Fidalgo 2012), unacylated ghrelin (D'Onofrio et al 2015;Togliatto et al 2014), and ginsenoside Rb1 (D'Onofrio et al 2015;Song et al 2014), a steroid glycoside found in ginseng and paeonol (D'Onofrio et al 2015;Jamal et al 2014). Resveratrol, a polyphenolic antioxidant found in red wine, activating SIRT1 (Villalba and Alcain 2012;Wallerath et al 2002) prevents oxidative stress and coronary VSMC proliferation inhibiting extracellular signal regulated kinase (ERK) activation (Chong et al 2012;El-Mowafy et al 2008).…”

Section: The Sirtuin Familymentioning

confidence: 99%

Sirtuins, aging, and cardiovascular risks

Favero

Franceschetti

Rodella

2015

AGE

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The sirtuins comprise a highly conserved family proteins present in virtually all species from bacteria to mammals. Sirtuins are members of the highly conserved class III histone deacetylases, and seven sirtuin genes (sirtuins 1-7) have been identified and characterized in mammals. Sirtuin activity is linked to metabolic control, apoptosis, cell survival, development, inflammation, and healthy aging. In this review, we summarize and discuss the potential mutual relations between each sirtuin and cardiovascular health and the impact of sirtuins on oxidative stress and so age-related cardiovascular disorders, underlining the possibility that sirtuins will be novel targets to contrast cardiovascular risks induced by aging.

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Paeonol protects against premature senescence in endothelial cells by modulating Sirtuin 1 pathway

Cited by 56 publications

References 36 publications

Curcumin Attenuates Hydrogen Peroxide-Induced Premature Senescence <i>via</i> the Activation of SIRT1 in Human Umbilical Vein Endothelial Cells

Curcumin Attenuates Hydrogen Peroxide-Induced Premature Senescence <i>via</i> the Activation of SIRT1 in Human Umbilical Vein Endothelial Cells

Gestational diabetes induces alterations of sirtuins in fetal endothelial cells

Sirtuins, aging, and cardiovascular risks

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