title: High-fat diet increases and the polyphenol, S17834, decreases acetylation of the sirtuin-1-dependent lysine-382 on p53 and apoptotic signaling in atherosclerotic lesion-prone aortic endothelium of normal mice.
abstract: Our purpose was to determine if high-fat diet and treatment with a polyphenol regulate the acetylation of lysine-382 of p53, the site regulated by sirtuin-1, and apoptosis in the endothelium of the atherosclerotic lesion-prone mouse aortic arch. In cultured endothelial cells, 2 atherogenic stimuli, hydrogen peroxide and tumor necrosis factor-α, increased the acetylation of p53 lysine-382, and caspase-3 cleavage, an indicator of apoptotic signaling. The polyphenol, S17834, significantly prevented these changes. In low-density lipoprotein receptor-deficient mice, a high-fat diet increased, and treatment with S17834 attenuated early atherosclerotic lesions on the lesser curvature of the aortic arch. In wild-type C57BL6 mice fed the same diet, no atherosclerotic lesions were observed in this lesion-prone area, but p53 acetylation and caspase-3 cleavage increased in the endothelium. In high-fat fed mice, S17834 increased sirtuin-1 protein in the lesion-prone endothelium and prevented both the increase in p53 acetylation and caspase-3 cleavage without affecting blood lipids. These results indicate that high-fat diet increases and S17834 decreases the acetylation of p53 in lesion-prone aortic endothelial cells of normal mice independently of blood lipids, suggesting that the polyphenol may regulate endothelial cell p53 acetylation and apoptosis via local actions.
authors.affiliation: Vascular Biology Section, Department of Medicine, Whitaker Cardiovascular Institute, Boston University School of Medicine, Boston, MA, USA.
authors.forename: Shanqin
authors.initials: S
authors.lastname: Xu
authors.forename: Bingbing
authors.initials: B
authors.lastname: Jiang
authors.forename: Xiuyun
authors.initials: X
authors.lastname: Hou
authors.forename: Chaomei
authors.initials: C
authors.lastname: Shi
authors.forename: Markus M
authors.initials: MM
authors.lastname: Bachschmid
authors.forename: Mengwei
authors.initials: M
authors.lastname: Zang
authors.forename: Tony J
authors.initials: TJ
authors.lastname: Verbeuren
authors.forename: Richard A
authors.initials: RA
authors.lastname: Cohen
mesh_terms: D000107:Acetylation; D000818:Animals; D001013:Aorta, Thoracic / Q000378:metabolism / Q000473:pathology; D017209:Apoptosis; D050197:Atherosclerosis / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology / Q000503:physiopathology; D001578:Benzopyrans / Q000378:metabolism / Q000493:pharmacokinetics / Q000494:pharmacology*; D053148:Caspase 3 / Q000378:metabolism; D002478:Cells, Cultured; D059305:Diet, High-Fat; D004195:Disease Models, Animal; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism; D000960:Hypolipidemic Agents / Q000378:metabolism / Q000494:pharmacology*; D008055:Lipids / Q000097:blood; D008239:Lysine / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D059808:Polyphenols / Q000378:metabolism / Q000493:pharmacokinetics / Q000494:pharmacology*; D015398:Signal Transduction; D056564:Sirtuin 1 / Q000378:metabolism*; D013481:Superoxides / Q000037:antagonists & inhibitors; D016159:Tumor Suppressor Protein p53 / Q000737:chemistry / Q000378:metabolism*
chemical_list: C438505:6,8-diallyl 5,7-dihydroxy 2-(2-allyl 3-hydroxy 4-methoxyphenyl)1-H benzo(b)pyran-4-one; D001578:Benzopyrans; D000960:Hypolipidemic Agents; D008055:Lipids; D059808:Polyphenols; D016159:Tumor Suppressor Protein p53; D013481:Superoxides; D053148:Caspase 3; D056564:Sirtuin 1; D008239:Lysine