イシズ　アヤコ   Ayako Nakamura-Ishizu   石津　綾子    所属   医学部 医学科    職種   教授・基幹分野長
論文種別	原著
言語種別	英語
査読の有無	査読あり
表題	Pathological neoangiogenesis depends on oxidative stress regulation by ATM.
掲載誌名	正式名：Nature medicine 略　 称：Nat Med ISSNコード：1546170X/10788956
掲載区分	国外
巻・号・頁	18(8),pp.1208-16
著者・共著者	Okuno Yuji, Nakamura-Ishizu Ayako, Otsu Kinya, Suda Toshio, Kubota Yoshiaki
発行年月	2012/08
概要	The ataxia telangiectasia mutated (ATM) kinase, a master regulator of the DNA damage response (DDR), acts as a barrier to cellular senescence and tumorigenesis. Aside from DDR signaling, ATM also functions in oxidative defense. Here we show that Atm in mice is activated specifically in immature vessels in response to the accumulation of reactive oxygen species (ROS). Global or endothelial-specific Atm deficiency in mice blocked pathological neoangiogenesis in the retina. This block resulted from increased amounts of ROS and excessive activation of the mitogen activated kinase p38α rather than from defects in the canonical DDR pathway. Atm deficiency also lowered tumor angiogenesis and enhanced the antiangiogenic action of vascular endothelial growth factor (Vegf) blockade. These data suggest that pathological neoangiogenesis requires ATM-mediated oxidative defense and that agents that promote excessive ROS generation may have beneficial effects in the treatment of neovascular disease.
DOI	10.1038/nm.2846
PMID	22797809