Mitochondrial peripheral-type benzodiazepine receptor expression. Correlation with gonadotropin-releasing hormone (GnRH) agonist-induced apoptosis in the corpus luteum.
Mitochondrial peripheral-type benzodiazepine receptor expression. Correlation with gonadotropin-releasing hormone (GnRH) agonist-induced apoptosis in the corpus luteum.
复制标题
线粒体外周型苯二氮卓受体表达。
DOI：
10.1016/s0006-2952(99)00215-4
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发表时间：
1999
影响因子：
5.8
通讯作者：
Sridaran,R
中科院分区：
文献类型：
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作者：
Papadopoulos,V;Dharmarajan,AM;Li,H;Culty,M;Lemay,M;Sridaran,R
我们已经证明，持续给予促性腺激素释放激素激动剂（GnRH-Ag）降低线粒体外周型苯二氮卓受体（PBR）的表达，并以一种时间依赖性的方式增加妊娠大鼠黄体中DNA降解的速度。在本研究中，我们原位显示了gnrh - ag诱导的DNA片段，并将DNA降解率的增加与线粒体PBR配体结合的减少联系起来（r = 0.89）。gnrh - ag诱导的18 kda PBR蛋白的降低也与黄体线粒体制剂中Bcl-XL的降低相关，但与Bcl-2（细胞存活）、基因产物水平和Bax（细胞死亡）基因产物表达的增加无关。考虑到PBR在胆固醇摄取和线粒体内运动中的功能，我们提出PBR表达减少可能导致线粒体膜胆固醇水平降低，而线粒体膜胆固醇水平与Bcl-XLand Bax形成离子通道的能力一起，在外膜上产生断裂，使细胞色素c退出，从而引发细胞凋亡。或者，PBR可能发挥一种尚未确定的抗凋亡功能。
We have demonstrated that continuous administration of a gonadotropin-releasing hormone agonist (GnRH-Ag) decreases the expression of the mitochondrial peripheral-type benzodiazepine receptor (PBR) and increases the rate of DNA degradation in a time-dependent manner in the corpora lutea of pregnant rats. In the present study, we show in situ the GnRH-Ag-induced DNA fragmentation and correlate the increase of the rate of DNA degradation with the decrease in mitochondrial PBR ligand binding (r = 0.89). The GnRH-Ag-induced decrease in the 18-kDa PBR protein also correlated with the reduction in the Bcl-XL, but not Bcl-2 (cell survival), gene product levels and the increase in the Bax (cell death) gene product expression in the luteal mitochondrial preparations. Considering the function of PBR in cholesterol uptake and intramitochondrial movement, we propose that decreased PBR expression may lead to reduced levels of mitochondrial membrane cholesterol, which, together with the ability of Bcl-XLand Bax to form ion channels, produces breaks in the outer membranes allowing the exit of cytochrome c, thus triggering apoptosis. Alternatively, PBR may exert an as yet unidentified anti-apoptotic function.