Gabai V L
Medical Radiology Research Center, Russian Academy of Medical Sciences, Obninsk.
FEBS Lett. 1993 Aug 23;329(1-2):67-71. doi: 10.1016/0014-5793(93)80195-z.
Uncouplers CCCP (2-4 microM) or DNP (200-400 microM) when added to EL-4 thymoma or Ehrlich carcinoma ascites cells initially stimulated endogenous respiration about 2-fold but then inhibited it to a first-order rate 20-25% of controls. This inhibition was accelerated by intracellular acidification or by A23187, a Ca2+/H(+)-antiporter (i.e. when mitochondrial Ca2+ efflux was stimulated) whereas Ruthenium red, an inhibitor of uniporter-driven Ca2+ efflux, significantly slowed down the effect of uncouplers. The respiratory inhibition was associated with NAD(P)H oxidation and was partially reversed by exogenous substrates (glutamine or glucose). In the permeabilized cells, endogenous and glutamine-supported respiration was inhibited by EGTA, while succinate-supported respiration was Ca2+ independent. It is suggested that mitochondrial Ca2+ is necessary for NADH-dependent respiration of tumor cells, and uncouplers inhibit it by activation of mitochondrial Ca2+ efflux.
解偶联剂CCCP（2 - 4微摩尔）或DNP（200 - 400微摩尔）添加到EL - 4胸腺瘤或艾氏腹水癌细胞中时，最初会使内源性呼吸增加约2倍，但随后会将其抑制至对照的20 - 25%的一级速率。细胞内酸化或Ca2+/H(+)反向转运体A23187（即刺激线粒体Ca2+外流时）会加速这种抑制作用，而单向转运体驱动的Ca2+外流抑制剂钌红则显著减缓了解偶联剂的作用。呼吸抑制与NAD(P)H氧化相关，并且可被外源性底物（谷氨酰胺或葡萄糖）部分逆转。在透化细胞中，EGTA抑制内源性和谷氨酰胺支持的呼吸，而琥珀酸支持的呼吸则不依赖Ca2+。提示线粒体Ca2+对于肿瘤细胞的NADH依赖性呼吸是必需的，解偶联剂通过激活线粒体Ca2+外流来抑制它。
