Humes H D
Am J Physiol. 1986 Apr;250(4 Pt 2):F579-89. doi: 10.1152/ajprenal.1986.250.4.F579.
The potential for calcium to play a key role in cell injury has been long suspected. Major sites of calcium action to promote cell injury include the plasma membrane, mitochondria, endoplasmic reticulum, and the cytoskeleton. Major mechanisms of calcium action to promote cell injury include activation of phospholipases, direct and indirect effects on permeability pathways, and effects on contractile and cytoskeletal structure and function. The activation of phospholipases and deterioration of mitochondrial structure and function by calcium appear to be most important in the evolution of cell injury. Tissue calcium levels invariably increase when lethal cell injury develops in a tissue and is due predominantly to mitochondrial accumulation and sequestration. The simultaneous occurrence of cell calcium overload and lethal cell injury, however, only establishes an association between these two events but does not prove causality. Over the past several years, a large amount of data has established that calcium plays a critical modifying role in the pathogenesis of both ischemic and toxic cell injury, but evidence for the thesis that calcium is the "final common pathway" for lethal cell injury is not conclusive. Many studies have emphasized the role of calcium influx from extracellular to intracellular spaces with resulting cellular calcium overload in cell injury. A critical role for intracellular redistribution of calcium pools rather than cellular calcium influx during the important early stages of cell injury may be more important. Modifying alterations in cell calcium redistribution or cellular calcium influx with a variety of agents has been beneficial in ameliorating the degree of cell injury in a number of experimental settings. It is still unclear whether these beneficial effects are due mainly to alterations of calcium-mediated processes that determine the reversibility of injury or are due to alterations in other critical metabolic processes not importantly influenced by calcium.
长期以来，人们一直怀疑钙在细胞损伤中可能发挥关键作用。钙促进细胞损伤的主要作用部位包括质膜、线粒体、内质网和细胞骨架。钙促进细胞损伤的主要作用机制包括磷脂酶的激活、对通透性途径的直接和间接影响，以及对收缩和细胞骨架结构与功能的影响。钙对磷脂酶的激活以及线粒体结构和功能的恶化在细胞损伤的发展过程中似乎最为重要。当组织发生致命性细胞损伤时，组织钙水平总是会升高，这主要是由于线粒体的积累和螯合作用。然而，细胞钙超载和致命性细胞损伤的同时出现，仅建立了这两个事件之间的关联，但并未证明因果关系。在过去几年中，大量数据表明钙在缺血性和中毒性细胞损伤的发病机制中起关键的调节作用，但钙是致命性细胞损伤的“最终共同途径”这一论点的证据并不确凿。许多研究强调了细胞外钙流入细胞内导致细胞钙超载在细胞损伤中的作用。在细胞损伤的重要早期阶段，钙池的细胞内重新分布而非细胞钙流入可能发挥更关键的作用。在许多实验环境中，用各种药物改变细胞钙重新分布或细胞钙流入，对减轻细胞损伤程度有益。目前尚不清楚这些有益作用主要是由于决定损伤可逆性的钙介导过程的改变，还是由于不受钙重要影响的其他关键代谢过程的改变。
