Belosludtsev Konstantin, Saris Nils-Erik L, Andersson Leif C, Belosludtseva Natalia, Agafonov Alexey, Sharma Ankit, Moshkov Dmitry A, Mironova Galina D
Institute of Theoretical and Experimental Biophysics RAS, Pushchino, Moscow Region, 142290, Russia.
J Bioenerg Biomembr. 2006 Apr;38(2):113-20. doi: 10.1007/s10863-006-9010-9. Epub 2006 Jul 18.
Palmitic acid (Pal) is known to promote apoptosis (Sparagna G et al (2000) Am J Physiol Heart Circ Physiol 279: H2124-H2132) and its amount in blood and mitochondria increases under some pathological conditions. Yet, the mechanism of the proapoptotic action of Pal has not been elucidated. We present evidence for the involvement of the mitochondrial cyclosporin A-insensitive pore induced by Pal/Ca(2+) complexes in the apoptotic process. Opening of this pore led to a fall of the mitochondrial membrane potential and the release of the proapoptotic signal cytochrome c. The addition of cytochrome c prevented these effects and recovered membrane potential, which is in contrast to the cyclosporin A-sensitive mitochondrial permeability transition pore. Oleic and linoleic acids prevented the Pal/Ca(2+)-induced pore opening in the intact mitochondria, this directly and significantly correlating with the effect of these fatty acids on Pal-induced apoptosis in cells (Hardy S et al (2003) J Biol Chem 278: 31861-31870). The specific probe for cardiolipin, 10-N-nonyl acridine orange, inhibited formation of this pore.
已知棕榈酸（Pal）可促进细胞凋亡（Sparagna G等人，2000年，《美国生理学杂志：心脏和循环生理学》279卷：H2124 - H2132），并且在某些病理条件下其在血液和线粒体中的含量会增加。然而，Pal促凋亡作用的机制尚未阐明。我们提供证据表明，由Pal/Ca(2+)复合物诱导的线粒体环孢菌素A不敏感孔参与了凋亡过程。该孔的开放导致线粒体膜电位下降以及促凋亡信号细胞色素c的释放。添加细胞色素c可防止这些效应并恢复膜电位，这与环孢菌素A敏感的线粒体通透性转换孔相反。油酸和亚油酸可防止完整线粒体中Pal/Ca(2+)诱导的孔开放，这直接且显著地与这些脂肪酸对细胞中Pal诱导的凋亡的影响相关（Hardy S等人，2003年，《生物化学杂志》278卷：31861 - 31870）。心磷脂的特异性探针10 - N - 壬基吖啶橙可抑制该孔的形成。
