title: Angiotensin II induces human astrocyte senescence through reactive oxygen species production.
abstract: Angiotensin II (Ang II)-induced astrocyte senescence may be involved in cerebral ischemic injury and age-associated neurodegenerative disease. This study was conducted to determine the roles of reactive oxygen species production in Ang II-induced cellular senescence in cultured human astrocytes. Human astrocytes were stimulated with Ang II either with or without an angiotensin type 1 receptor blocker, CV11974, or an antioxidant, tempol. Application of Ang II to human astrocytes resulted in a concentration-dependent increase in staining for dihydroethidium. Ang II (100 nM for 30 min) increased the translocation of two cytosolic components of NADPH oxidase, p47phox and p67phox, to the cell membrane and formation of the complex of p47phox, p67phox and p22phox. Ang II concentration-dependently induced an increase in β-galactosidase staining. Pretreatment with CV11974 (100 nM) or tempol (3 mM) abolished Ang II-induced astrocyte β-galactosidase staining. Moreover, Ang II significantly upregulated p16 mRNA expression, which was inhibited by pretreatment with CV11974 or tempol. These findings indicate that superoxide production contributes to Ang II-induced astrocyte senescence.
authors.affiliation: Department of Pharmacology, Kagawa University School of Medicine, Kagawa, Japan.
authors.forename: Gang
authors.initials: G
authors.lastname: Liu
authors.forename: Naohisa
authors.initials: N
authors.lastname: Hosomi
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Hitomi
authors.forename: Nicolas
authors.initials: N
authors.lastname: Pelisch
authors.forename: Hua
authors.initials: H
authors.lastname: Fu
authors.forename: Hisashi
authors.initials: H
authors.lastname: Masugata
authors.forename: Koji
authors.initials: K
authors.lastname: Murao
authors.forename: Masaki
authors.initials: M
authors.lastname: Ueno
authors.forename: Masayasu
authors.initials: M
authors.lastname: Matsumoto
authors.forename: Akira
authors.initials: A
authors.lastname: Nishiyama
mesh_terms: D000804:Angiotensin II / Q000494:pharmacology*; D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology; D000975:Antioxidants / Q000494:pharmacology; D001253:Astrocytes / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D001562:Benzimidazoles / Q000494:pharmacology; D001713:Biphenyl Compounds; D002478:Cells, Cultured; D016922:Cellular Senescence / Q000187:drug effects*; D003497:Cyclic N-Oxides / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D006801:Humans; D019255:NADPH Oxidases / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism*; D013113:Spin Labels; D013481:Superoxides / Q000378:metabolism; D013777:Tetrazoles / Q000494:pharmacology
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D000975:Antioxidants; D001562:Benzimidazoles; D001713:Biphenyl Compounds; D003497:Cyclic N-Oxides; D017382:Reactive Oxygen Species; D013113:Spin Labels; D013777:Tetrazoles; D013481:Superoxides; D000804:Angiotensin II; D019255:NADPH Oxidases; C081643:candesartan; C001803:tempol