Prohibitin-1 maintains the angiogenic capacity of endothelial cells by regulating mitochondrial function and senescence.
Prohibitin-1 maintains the angiogenic capacity of endothelial cells by regulating mitochondrial function and senescence.
复制标题
禁止素-1通过调节线粒体功能和衰老来维持内皮细胞的血管生成能力。
DOI：
10.1083/jcb.200706072
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发表时间：
2008-01-14
影响因子：
7.8
通讯作者：
Sessa, William C.
中科院分区：
文献类型：
--
作者：
Schleicher, Michael;Shepherd, Benjamin R.;Suarez, Yajaira;Fernandez-Hernando, Carlos;Yu, Jun;Pan, Yong;Acevedo, Lisette M.;Shadel, Gerald S.;Sessa, William C.
Prohibitin 1(PHB1)是一种高度保守的蛋白质，主要定位于线粒体内膜，参与酵母线粒体功能的调节。由于线粒体正在成为血管内稳态的重要调节器，我们检测了内皮细胞中PHB1的功能。PHB1在血管系统中高表达，内皮细胞中PHB1的敲除通过抑制复合体I而增加线粒体产生的活性氧物种，从而导致细胞衰老。直接的结果是，Akt和rac1都被过度激活，导致细胞骨架重排和内皮细胞运动性降低，例如迁移和管状形成。这也反映在体内的血管生成试验中，PHB1的沉默阻止了功能性血管的形成。总之，我们的结果提供了证据，证明PHB1对线粒体功能和防止活性氧诱导的衰老，从而维持内皮细胞的血管生成能力是重要的。
Prohibitin 1 (PHB1) is a highly conserved protein that is mainly localized to the inner mitochondrial membrane and has been implicated in regulating mitochondrial function in yeast. Because mitochondria are emerging as an important regulator of vascular homeostasis, we examined PHB1 function in endothelial cells. PHB1 is highly expressed in the vascular system and knockdown of PHB1 in endothelial cells increases mitochondrial production of reactive oxygen species via inhibition of complex I, which results in cellular senescence. As a direct consequence, both Akt and Rac1 are hyperactivated, leading to cytoskeletal rearrangements and decreased endothelial cell motility, e.g., migration and tube formation. This is also reflected in an in vivo angiogenesis assay, where silencing of PHB1 blocks the formation of functional blood vessels. Collectively, our results provide evidence that PHB1 is important for mitochondrial function and prevents reactive oxygen species–induced senescence and thereby maintains the angiogenic capacity of endothelial cells.
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DOI：
10.1073/pnas.92.20.9363
发表时间：
1995-09-26
影响因子：
11.1
作者：
DIMRI, GP;LEE, XH;CAMPISI, J
通讯作者：
CAMPISI, J
影响因子：
9.2
作者：
Coates, PJ;Jamieson, DJ;Hall, PA
通讯作者：
Hall, PA
影响因子：
4.8
作者：
Connor, KM;Subbaram, S;Melendez, JA
通讯作者：
Melendez, JA
影响因子：
4.8
作者：
Fusaro, G;Dasgupta, P;Chellappan, S
通讯作者：
Chellappan, S
影响因子：
7.4
作者：
Du, G;Mouithys-Mickalad, A;Sluse, FE
通讯作者：
Sluse, FE