Chowdhury Anindya Roy, Ghosh Ilora, Datta Kasturi
Biochemistry Laboratory, School of Environmental Sciences, Jawaharlal Nehru University, New Delhi-110067, India.
Exp Cell Res. 2008 Feb 1;314(3):651-67. doi: 10.1016/j.yexcr.2007.10.033. Epub 2007 Nov 21.
Constitutively expressed HABP1 in normal murine fibroblast cell line induces growth perturbation, morphological abnormalities along with initiation of apoptosis. Here, we demonstrate that though HABP1 accumulation started in mitochondria from 48 hr of growth, induction of apoptosis with the release of cytochrome c and apoptosome complex formation occurred only after 60 hr. This mitochondrial dysfunction was due to gradual increase in ROS generation in HABP1 overexpressing cells. Along with ROS generation, increased Ca 2+ influx in mitochondria leading to drop in membrane potential was evident. Interestingly, upon expression of HABP1, the respiratory chain complex I was shown to be significantly inhibited. Electronmicrograph confirmed defective mitochondrial ultrastructure. The reduction in oxidant generation and drop in apoptotic cell population accomplished by disruption of HABP1 expression, corroborating the fact that excess ROS generation in HABP1 overexpressing cells leading to apoptosis was due to mitochondrial HABP1 accumulation.
在正常小鼠成纤维细胞系中组成性表达的HABP1会诱导生长紊乱、形态异常以及凋亡的启动。在此，我们证明，虽然HABP1的积累在生长48小时后开始于线粒体，但细胞色素c的释放和凋亡小体复合物的形成所诱导的凋亡仅在60小时后发生。这种线粒体功能障碍是由于HABP1过表达细胞中活性氧（ROS）生成的逐渐增加。随着ROS的生成，线粒体中钙离子内流增加导致膜电位下降是明显的。有趣的是，在HABP1表达后，呼吸链复合物I被证明受到显著抑制。电子显微镜证实了线粒体超微结构的缺陷。通过破坏HABP1的表达实现了氧化剂生成的减少和凋亡细胞群体的下降，这证实了HABP1过表达细胞中过量ROS生成导致凋亡是由于线粒体HABP1积累这一事实。
