Activation of BKCa channel is associated with increased apoptosis of cerebrovascular smooth muscle cells in simulated microgravity rats
Activation of BKCa channel is associated with increased apoptosis of cerebrovascular smooth muscle cells in simulated microgravity rats
复制标题
BKCa 通道的激活与模拟微重力大鼠脑血管平滑肌细胞凋亡的增加有关。
DOI：
10.1152/ajpcell.00474.2009
复制
发表时间：
2010-06-01
影响因子：
5.5
通讯作者：
Ma, Jin
中科院分区：
文献类型：
--
作者：
Xie, Man-Jiang;Ma, Yu-Guang;Ma, Jin
脑动脉重构是航天后立位耐力不良发生的重要因素之一。我们推测血管平滑肌细胞（VSMCs）中的大电导钙激活钾（+）（BK（Ca））通道可能在微重力暴露期间调节脑血管适应中起重要作用。本工作的目的是研究BK（Ca）通道的激活是否参与模拟微重力大鼠脑动脉的凋亡重构的调节。在动物研究中，对Sprague-Dawley大鼠进行为期1周的后肢减重，以模拟微重力。采用膜片钳和Western blotting方法观察脑VSMCs BK（Ca）通道的变化，采用电镜和末端脱氧核苷酸转移酶介导的dUTP-生物素缺口末端标记法（TUNEL）检测细胞凋亡。为探讨BK（Ca）通道与细胞凋亡的相关性，对通道蛋白和细胞核进行双染。在细胞研究中，将hSloalpha+beta1通道共表达于人胚肾293（HEK 293）细胞中，观察BK（Ca）通道对细胞凋亡的影响。在大鼠中，BK（Ca）通道的活性和表达增强与模拟微重力后脑VSMCs凋亡增加相关。在转染的HEK 293细胞中，激活克隆的BK（Ca）通道可诱导凋亡，而抑制克隆的BK（Ca）通道可降低凋亡。总之，BK（Ca）通道的激活与模拟微重力大鼠脑VSMCs凋亡增加有关。
Cerebral arterial remodeling is one of the critical factors in the occurrence of postspaceflight orthostatic intolerance. We hypothesize that large-conductance calcium-activated K(+) (BK(Ca)) channels in vascular smooth muscle cells (VSMCs) may play an important role in regulating cerebrovascular adaptation during microgravity exposure. The aim of this work was to investigate whether activation of BK(Ca) channels is involved in regulation of apoptotic remodeling of cerebral arteries in simulated microgravity rats. In animal studies, Sprague-Dawley rats were subjected to 1-wk hindlimb unweighting to simulate microgravity. Alterations of BK(Ca) channels in cerebral VSMCs were investigated by patch clamp and Western blotting; apoptosis was assessed by electron microscopy and terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick-end labeling (TUNEL). To evaluate the correlation of BK(Ca) channel and apoptosis, channel protein and cell nucleus were double-stained. In cell studies, hSloalpha+beta1 channel was coexpressed into human embryonic kidney 293 (HEK293) cells to observe the effects of BK(Ca) channels on apoptosis. In rats, enhanced activities and expression of BK(Ca) channels were found to be correlated with increased apoptosis in cerebral VSMCs after simulated microgravity. In transfected HEK293 cells, activation of cloned BK(Ca) channel induced apoptosis, whereas inhibition of cloned BK(Ca) channel decreased apoptosis. In conclusion, activation of BK(Ca) channels is associated with increased apoptosis in cerebral VSMCs of simulated microgravity rats.