Ectopic localization of mitochondrial ATP synthase: A target for anti-angiogenesis intervention?
Ectopic localization of mitochondrial ATP synthase: A target for anti-angiogenesis intervention?
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DOI：
10.1007/s10863-005-9492-x
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发表时间：
2005-12-01
影响因子：
3
通讯作者：
Wahl, ML
中科院分区：
文献类型：
--
作者：
Kenan, DJ;Wahl, ML
血管抑素受体被鉴定为血管内皮细胞表面的F1F0ATP合成酶(Moser等人，1999)。程序没有。阿西德。SCI。美国96,2811-2816。这种异位的三磷酸腺苷合成酶催化三磷酸腺苷的合成，并在很宽的pH范围内被血管抑素抑制。在正常pH下生长的内皮细胞在血管抑素介导的对ATP合成酶的抑制之前没有不良影响，而在低的肿瘤样细胞外pH下生长的内皮细胞不能维持正常的细胞内pH而死亡。Angiostatin抑制ATP合成和ATP水解(Moser等人，2001)，并干扰细胞内pH调节(Wahl和Grant，2002；Wahl等人。2002年)。虽然静脉注射的血管抑素在几分钟内就能从循环中清除，但更稳定的血管抑素类药物具有临床应用的潜力。最近使用抗ATP合成酶的β催化亚基的多克隆抗体观察到了血管抑素的模拟活性。为了探索血管抑素及其模拟物的作用机制，还需要进一步的工作来评估这类药物的临床适用性、特异性和禁忌症。
A receptor for angiostatin was identified oil the surface of endothelial cells as F1F0 ATP synthase (Moser et al., 1999). Proc. Nall. Accid. Sci. U.S.A. 96, 2811-2816. This ectopic ATP synthase catalyzes ATP synthesis and is inhibited by angiostatin over a wide pH range. Endothelial cells grown at normal pH stiffer no ill effects front this angiostatin-mediated inhibition of ATP synthase, whereas endothelial cells grown at low, tumour-like extracellular pH cannot maintain a normal intracellular pH and die. Angiostatin inhibits both ATP synthesis and ATP hydrolysis (Moser et al., 2001) and interferes with intracellular pH regulation (Wahl and Grant, 2002; Wahl et al.. 2002). Although angiostatin administered intravenously is cleared from the circulation in a matter of minutes, angiostatinmimetics that are more stable have potential for clinical application. An angiostatin-mimetic activity has recently been observed Using a polyclonal antibody against the beta catalytic subunit of ATP synthase. In order to explore the mechanism of action of angiostatin and its mimetics, further work needs to be done to evaluate clinical applicability, specificity, and contraindicalions for this class of therapeutics.