Cytosolic Free Calcium and Cell Injury in Hepatocytes
Formation of cell surface blebs is an early event in hypoxic and toxic injury to liver (Lemasterset al., 1981, 1983; Jewellet al., 1982). Many authors have proposed that a rise of cytosolic free Ca2+ is the stimulus for bleb formation and the initiating factor in a sequence of events leading to irreversible injury and cell death (see Schanneet al., 1979; Trumpet al., 1980; Bellomo and Orrenius, 1985). Recently, we applied the technique of digitized video microscopy to quantitate changes in cytosolic free Ca2+ in relation to blebbing and other cellular parameters during “chemical hypoxia” with metabolic inhibitors in single cultured hepatocytes (Lemasterset al., 1987). Here we present new data examining the relation of bleb formation to the onset of cell death during cellular injury induced by a variety of toxic chemicals. We also determine whether changes in cytosolic free Ca2+ occur during cellular injury which might initiate bleb formation and lead to cell death. The results indicate that the onset of cell death is a very rapid event initiated by rupture of a large plasma membrane bleb leaving the cell in a hyperpermeable state. An increase in cytosolic free Ca2+ is not a necessity for the progression of bleb formation or the onset of cell death.
KeywordsPropidium Iodide Iodoacetic Acid Cytosolic Free Calcium Acetoxymethyl Ester Irreversible Injury
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