CALCIUM AND PH IN ANOXIC AND TOXIC INJURY

被引:74
作者
HERMAN, B
GORES, GJ
NIEMINEN, AL
KAWANISHI, T
HARMAN, A
LEMASTERS, JJ
机构
[1] UNIV WESTERN AUSTRALIA, DEPT PHARMACOL, NEDLANDS, WA 6009, AUSTRALIA
[2] NATL INST HYG SCI, DIV PHARMACOL, SETAGAYA KU, TOKYO 158, JAPAN
关键词
D O I
10.3109/10408449009089876
中图分类号
R99 [毒物学(毒理学)];
学科分类号
100405 ;
摘要
The critical events that lead to the transition from reversible to irreversible injury remain unclear. Studies are reviewed that have suggested that a rise in cytosolic free Ca2+ initiates plasma membrane bleb formation and a sequence of events that leads ultimately to cell death. In recent studies, we have measured changes in cytosolic free Ca2+, mitochondrial membrane potential, cytosolic pH, and cell surface blebbing in relation to the onset of irreversible injury and cell death following anoxic and toxic injury to single hepatocytes utilizing multiparameter digitized video microscopy (MDVM). MDVM is an emerging new technology that permits single living cells to be labeled with multiple probes whose fluorescence is responsive to specific cellular parameters of interest. Fluorescence images specific for each probe are collected over time, and then digitized and stored. Image analysis and processing then permits quantitation of the spatial distribution of the various parameters within the single living cells. Our results indicate the following: (1) formation of plasma membrane blebs accompanies all types of injury in hepatocytes; (2) cell death is a rapid event, initiated by rupture of a plasma membrane bleb, and is coincident with the onset of irreversible injury; (3) an increase of cytosolic free Ca2+ is not the stimulus for bleb formation or the final common pathway leading to cell death; (4) a decrease of mitochondrial membrane potential precedes loss of cell viability; (5) cytosolic pH falls by more than 1 pH unit during chemical hypoxia. This acidosis protects against the onset of cell death.
引用
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页码:127 / 148
页数:22
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