Richter C, Gogvadze V, Schlapbach R, Schweizer M, Schlegel J
Laboratory of Biochemistry I, Swiss Federal Institute of Technology, Zürich.
Biochem Biophys Res Commun. 1994 Dec 15;205(2):1143-50. doi: 10.1006/bbrc.1994.2785.
We have recently shown (Schweizer, M., and Richter, C. (1994) Biochem. Biophys. Res. Commun. 204, 169-175) that nitric oxide (nitrogen monoxide, NO) at low concentrations potently and reversibly deenergizes isolated liver and brain mitochondria at oxygen concentrations that prevail in cells and tissues. We now report that also in freshly prepared hepatocytes NO deenergizes mitochondria. Deenergization is reversible at low, but longer-lasting at higher NO concentrations. The drop and the recovery of the mitochondrial membrane potential are accompanied by a rise and fall of cytosolic Ca2+ levels. At higher concentrations NO kills hepatocytes. Killing is reduced when the cytosolic Ca2+ is chelated, or when the cyclic uptake and release of Ca2+ ("Ca2+ cycling") by mitochondria is prevented. We conclude that NO can kill cells by deenergizing mitochondria and thereby flooding the cytosol with Ca2+.
我们最近已经表明（施韦泽，M.，和里希特，C.（1994年）《生物化学与生物物理研究通讯》204，169 - 175），在细胞和组织中普遍存在的氧浓度下，低浓度的一氧化氮（二氧化氮，NO）能有效且可逆地使分离的肝脏和脑线粒体失去能量。我们现在报告，在新鲜制备的肝细胞中，NO也会使线粒体失去能量。在低浓度时，能量丧失是可逆的，但在较高NO浓度下持续时间更长。线粒体膜电位的下降和恢复伴随着胞质Ca2 +水平的升高和降低。在较高浓度下，NO会杀死肝细胞。当胞质Ca2 +被螯合，或者当线粒体对Ca2 +的循环摄取和释放（“Ca2 +循环”）被阻止时，细胞死亡减少。我们得出结论，NO可以通过使线粒体失去能量，从而使胞质充满Ca2 +来杀死细胞。
