The Role of Ionized Cytosolic Calcium ([Ca2+]i) in Acute and Chronic Cell Injury
In 1971, we introduced an hypothesis concerning the role of ion deregulation in cell injury (Trump et al., 1971). At that time, using technologies such as atomic absorption and flame photomtery, we observed that deregulation of sodium, chloride, potassium, and calcium proceed in sequence with regard to the acute effects of cell injury leading to necrosis. This hypothesis has been modified during the last several years as new technologies have developed. Although calcium precipitates have long been known in pathology as representing areas of cell injury and usually cell death, more recently we have had the opportunity to examine the effects of calcium as a messenger of cell death. For some time, free ionized cytosolic calcium ([Ca2+]i) has been noted as a first or second messenger following a variety of stimuli including growth factors in both fibroblasts and epithelia. It is very striking, however, that the effects of injurious agents, such as HgCl2, often mimic the effects of growth factors and, indeed, may well be growth factors involved in regeneration of cells at the edge of necrotic areas. In studies of chronic toxicity, it has become apparent that many non-mutagenic, injurious chemicals, such as saccharine, nitrilotriacetic acid and hypolipidemic agents can result in neoplasia. Moreover, virtually all mutagenic carcinogens, prior to the development of cancer, lead to both acute and chronic cell injury including necrosis and acute and chronic inflammation. The link between cell injury and neoplasia, therefore, needs much further clarification and, extending our previous hypothesis (Trump and Berezesky, 1985, 1987a-d; Trump et al., 1981, 1984), we propose that deregulation of [Ca2+]i and possibly intracellular pH (pHi) represents this link between cell injury, cell death, and neoplasia.
KeywordsCell Injury Nitrilotriacetic Acid Normal Human Bronchial Epithelial Cell Emergency Medical Service System Bleb Formation
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