The role of Ca2+ in cell killing.
The role of Ca2+ in cell killing.
复制标题
Ca2 在细胞杀伤中的作用。
DOI：
10.1021/tx00018a001
复制
发表时间：
1990
影响因子：
4.1
通讯作者：
S. Orrenius
中科院分区：
文献类型：
--
作者：
P. Nicotera;G. Bellomo;S. Orrenius
The involvement of Ca2+ in the regulation of a large number of physiological processes is now well established. Along with this knowledge has come the understanding that Ca2+ can also play a determinant role in a variety of pathological and toxicological processes. It has long been recognized that Ca2+ accumulates in necrotic tissue (1, 2), and subsequent work has revealed that a disruption of intracellular Ca2+ homeostasis is frequently associated with the early development of cell injury (3, 4). This led to the formation of the Ca2+ hypothesis of cell injury, proposing that disruption of the intracellular Ca2+ homeostasis may be a common step in the development of cytotoxicity (3). The possible involvement of changes in intracellular Ca2+ homeostasis in cell killing by toxic agents has since been debated.During thepast several years it has become progressively clear that sustained increases in intracellular Ca2+ can activate cytotoxic mechanisms associated with irreversible injury in various cell systems and organs (Figure 1). Thus, Ca2+ appears to mediate theneurotoxicity of cyanide, chlordecone, and heavy metals, including lead, mercury, and organotin compounds (see ref 5 for review). In ad-dition, intracellular Ca2+ accumulation due to excessive stimulation of excitatory amino acid receptors (6) and enhanced Ca2+ influx through membrane channels (7) appears toplay an important role in brain ischemia. An elevation of intracellular Ca2+ also seems to contribute to cell killing by several hepatotoxic agents, such as acet-aminophen (8-10), diquat and CC14 (10), quinones (11), cyanide (12), and maitotoxin, a polyhydroxy polyether compound that stimulates intracellular Ca2+ accumulation (13). An increased intracellular Ca2+ level has also been reported to be the determinant factor in the development of cardiotoxicity following exposure to the environmental contaminant TCDD (14) and in thymocyte killing by TCDD and tributyltin (15, 16). Moreover, intracellular Ca2+ overload is involved in the development of reperfusion injury in the heart (17) and oxidative damage to kidney membranes during cold ischemia (18). There is also increasing evidence that Ca2+ plays an important role in cell killing in the immune system. Thus, the killing of immature thymocytes by glucocorticoids (19, 20), the killing of target cells bycytotoxic T lymphocytes (21) and by natural killer cells (22), and complement-mediated cell killing (23) all appear to be Ca2+-dependent. Finally, re-
