Aw T Y, Jones D P
Department of Biochemistry, Emory University School of Medicine, Atlanta, Georgia 30322.
Am J Physiol. 1989 Sep;257(3 Pt 1):C435-41. doi: 10.1152/ajpcell.1989.257.3.C435.
The effect of cyanide on cell viability and mitochondrial function was studied in hepatocytes exposed to air or argon. Cells were more susceptible to cyanide toxicity under air than under argon. Analysis of the disposition of cyanide showed that the difference in susceptibility to KCN was not due to O2-dependent differences in cyanide metabolism or elimination. Studies of mitochondrial function revealed that cyanide under aerobic conditions resulted in substantial swelling of the mitochondria, which corresponded to a matrix loading of phosphate. In addition, cyanide caused a loss of the mitochondrial protonmotive force. This was in contrast to the results for cells exposed to 30 min of anoxia alone in which there was no loss of mitochondrial delta pH, no detectable change in mitochondrial volume, and little matrix loading of phosphate. These results show that at least some of the protective mechanisms elicited by anoxia (B. S. Andersson, T. Y. Aw, and D. P. Jones. Am. J. Physiol. 252 (Cell Physiol. 21): C349-C355, 1987) are not elicited by cyanide alone. Thus cyanide under aerobic conditions does not provide a completely valid model for simple anoxia. Moreover, the results suggest that the molecular sensor necessary to signal suppression of metabolic and transport functions during neahypoxia is dependent on O2 and is neither stimulated nor antagonized by KCN.
研究了氰化物对暴露于空气或氩气中的肝细胞的细胞活力和线粒体功能的影响。与氩气环境相比，细胞在空气环境下对氰化物毒性更敏感。氰化物处置分析表明，对氰化钾敏感性的差异并非由于氰化物代谢或消除过程中氧气依赖的差异所致。线粒体功能研究显示，有氧条件下的氰化物会导致线粒体大量肿胀，这与磷酸盐的基质负载相对应。此外，氰化物会导致线粒体质子动力丧失。这与单独暴露于30分钟缺氧环境的细胞结果形成对比，在缺氧环境下线粒体δpH没有丧失，线粒体体积没有可检测到的变化，且磷酸盐的基质负载很少。这些结果表明，缺氧引发的至少一些保护机制（B. S. 安德森、T. Y. 奥和D. P. 琼斯。《美国生理学杂志》252卷（细胞生理学21）：C349 - C355，1987年）并非仅由氰化物引发。因此，有氧条件下的氰化物不能为单纯缺氧提供一个完全有效的模型。此外，结果表明，在接近缺氧期间信号抑制代谢和转运功能所需的分子传感器依赖于氧气，且不受氰化钾刺激或拮抗。
