Angiotensin II induces human astrocyte senescence through reactive oxygen species production
Angiotensin II induces human astrocyte senescence through reactive oxygen species production
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DOI：
10.1038/hr.2010.269
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发表时间：
2011-04-01
影响因子：
5.4
通讯作者：
Nishiyama, Akira
中科院分区：
文献类型：
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作者：
Liu, Gang;Hosomi, Naohisa;Nishiyama, Akira
血管紧张素 II (Ang II) 诱导的星形胶质细胞衰老可能与脑缺血损伤和年龄相关的神经退行性疾病有关。本研究旨在确定活性氧产生在血管紧张素 II 诱导的培养人星形胶质细胞细胞衰老中的作用。使用 Ang II 刺激人星形胶质细胞，无论是否使用 1 型血管紧张素受体阻滞剂 CV11974 或抗氧化剂 tempol。将 Ang II 应用于人星形胶质细胞导致二氢乙锭染色呈浓度依赖性增加。 Ang II（100 nM，30 分钟）增加了 NADPH 氧化酶的两种胞质成分（p47phox 和 p67phox）向细胞膜的易位以及 p47phox、p67phox 和 p22phox 复合物的形成。 Ang II浓度依赖性地诱导β-半乳糖苷酶染色的增加。用 CV11974 (100 nM) 或 tempol (3 mM) 预处理消除了 Ang II 诱导的星形胶质细胞 β-半乳糖苷酶染色。此外，Ang II 显着上调 p16 mRNA 表达，而该表达可被 CV11974 或 tempol 预处理所抑制。这些发现表明超氧化物的产生有助于 Ang II 诱导的星形胶质细胞衰老。高血压研究 (2011) 34, 479-483; doi：10.1038/hr.2010.269； 2011 年 1 月 27 日在线发布
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 beta-galactosidase staining. Pretreatment with CV11974 (100 nM) or tempol (3 mM) abolished Ang II-induced astrocyte beta-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. Hypertension Research (2011) 34, 479-483; doi:10.1038/hr.2010.269; published online 27 January 2011