The role of glutathione in the retention of Ca2+ by liver mitochondria.
The role of glutathione in the retention of Ca2+ by liver mitochondria.
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DOI：
10.1016/s0021-9258(17)43600-3
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发表时间：
1984-01
期刊：
影响因子：
--
通讯作者：
M. C. Beatrice;D. L. Stiers;D. Pfeiffer
中科院分区：
文献类型：
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作者：
M. C. Beatrice;D. L. Stiers;D. Pfeiffer
大黄酸和呋喃妥因的浓度在微摩尔范围内诱导Ca 2+的释放和发展增加的内膜通透性在肝线粒体。两种化合物均抑制线粒体谷胱甘肽还原酶，导致GSH耗竭和GSSG在通电线粒体中蓄积。在这些条件下，化合物还改变吡啶核苷酸的氧化态，NADH被氧化，而NADPH保持还原。使用大黄酸或呋喃妥因，与叔丁基氢过氧化物和β-羟基丁酸酯一起，可以选择性地改变NAD/NADH、NADP/NADPH和GSSG/GSH比率，并确定这些不同状态对Ca 2+产生可渗透内膜的能力的影响。未观察到吡啶核苷酸比率与对Ca 2+的敏感性之间的相关性。当GSH含量高时，线粒体对Ca 2+是稳定的，但当Ca 2+存在且GSH转化为GSSG时，线粒体变得可渗透。有人提出，GSSG/GSH的比例，通过控制关键巯基的还原状态，调节溶血磷脂酰基转移酶的活性，因此，线粒体的能力，以保持不可渗透的激活后，线粒体内的Ca 2+需要磷脂酶A2。
Concentrations of rhein and nitrofurantoin in the micromolar range induce Ca2+ release and the development of increased inner membrane permeability in liver mitochondria. Both compounds inhibit the mitochondrial glutathione reductase causing a depletion of GSH and an accumulation of GSSG in energized mitochondria. Under these conditions, the compounds also alter the oxidation state of pyridine nucleotides, NADH becoming oxidized while NADPH remains reduced. Using rhein or nitrofurantoin, together with t-butyl-hydroperoxide and beta-hydroxybutyrate, it is possible to selectively alter the NAD/NADH, the NADP/NADPH, and the GSSG/GSH ratios and to determine the effect of these different states on the ability of Ca2+ to produce a permeable inner membrane. No correlation between pyridine nucleotide ratios and sensitivity to Ca2+ was observed. Mitochondria are stable to Ca2+ when the GSH content is high, but become permeable when Ca2+ is present and GSH is converted to GSSG. It is proposed that the GSSG/GSH ratio, by controlling the reduction state of critical sulfhydryl groups, regulates lysophospholipid acyltransferase activity and, therefore, the ability of mitochondria to remain impermeable upon activation of the intramitochondrial Ca2+ requiring phospholipase A2.