Richter C
Laboratory of Biochemistry I, Swiss Federal Institute of Technology (ETH), Zürich.
FEBS Lett. 1993 Jun 28;325(1-2):104-7. doi: 10.1016/0014-5793(93)81423-w.
Apoptosis is a physiological process for active cell removal. One of its hallmarks is an increased cytosolic Ca2+ content. Several genes involved in apoptosis control have been identified, but their mode of action is not understood in detail. Apoptosis may relate to oncogenesis, in that some malignant tumors may grow because genes engaged in apoptosis control are altered. L929 cells overexpressing the proto-oncogene bcl-2 have an increased mitochondrial membrane potential (delta psi), as have many carcinoma cells. bcl-2 protects L929 cells against apoptosis caused by pro-oxidant-induced mitochondrial Ca2+ 'cycling' and increased cytosolic Ca2+ levels. Nerve growth factor, which induces catalase, and inhibitors of mitochondrial Ca2+ release also prevent apoptosis. It is suggested that a pro-oxidant-induced Ca2+ release from mitochondria, followed by Ca2+ cycling and ATP depletion, is a common basic event during apoptosis. Accordingly, maintenance of delta psi stabilizes mitochondria, thereby prevents apoptosis, and may confer increased growth potential to cells.
细胞凋亡是一种主动清除细胞的生理过程。其特征之一是胞质Ca2+含量增加。已经鉴定出几种参与细胞凋亡控制的基因，但其作用方式尚不清楚。细胞凋亡可能与肿瘤发生有关，因为一些恶性肿瘤可能由于参与细胞凋亡控制的基因发生改变而生长。过表达原癌基因bcl-2的L929细胞具有增加的线粒体膜电位（Δψ），许多癌细胞也是如此。bcl-2保护L929细胞免受由促氧化剂诱导的线粒体Ca2+“循环”和胞质Ca2+水平升高引起的细胞凋亡。诱导过氧化氢酶的神经生长因子以及线粒体Ca2+释放抑制剂也可预防细胞凋亡。有人提出，促氧化剂诱导的线粒体Ca2+释放，随后是Ca2+循环和ATP耗竭，是细胞凋亡期间常见的基本事件。因此，维持Δψ可使线粒体稳定，从而防止细胞凋亡，并可能赋予细胞增加的生长潜力。
