title: Curcumin Attenuates Hydrogen Peroxide-Induced Premature Senescence via the Activation of SIRT1 in Human Umbilical Vein Endothelial Cells.
abstract: 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 (H2O2)-induced endothelial premature senescence and the mechanisms involved. Human umbilical vein endothelial cells (HUVECs) were cultured, and premature senescence was induced with 100 µM H2O2. Results showed that pretreatment with curcumin significantly attenuated the H2O2-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 H2O2-treated HUVECs. Treatment of HUVECs with H2O2 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 H2O2-induced premature senescence. These findings suggest that curcumin could attenuate oxidative stress-induced HUVECs' premature senescence via the activation of SIRT1.
authors.affiliation: Department of Cardiology, Renmin Hospital of Wuhan University.
authors.forename: Yueliu
authors.initials: Y
authors.lastname: Sun
authors.forename: Xiaorong
authors.initials: X
authors.lastname: Hu
authors.forename: Gangying
authors.initials: G
authors.lastname: Hu
authors.forename: Changwu
authors.initials: C
authors.lastname: Xu
authors.forename: Hong
authors.initials: H
authors.lastname: Jiang
mesh_terms: D000975:Antioxidants / Q000494:pharmacology; D017209:Apoptosis; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D016922:Cellular Senescence / Q000187:drug effects*; D030024:Curcuma / Q000737:chemistry*; D003474:Curcumin / Q000494:pharmacology*; D015536:Down-Regulation; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D010766:Phosphorylation; D010936:Plant Extracts / Q000494:pharmacology; D034741:RNA, Small Interfering; D056564:Sirtuin 1 / Q000378:metabolism*; D001616:beta-Galactosidase / Q000378:metabolism
chemical_list: D000975:Antioxidants; D010936:Plant Extracts; D034741:RNA, Small Interfering; D009569:Nitric Oxide; D006861:Hydrogen Peroxide; C496314:NOS3 protein, human; D052250:Nitric Oxide Synthase Type III; C061901:GLB1 protein, human; D001616:beta-Galactosidase; D056564:Sirtuin 1; D003474:Curcumin