Biochemical mechanisms involved in toxic cell injury have attracted inÂ creased interest during recent years and have been the subject of several reviews (1-6). In this chapter we discuss one particular aspect of chemically induced cell death, i.e. the role of the calcium ion in the early development of damage. We summarize current evidence for an association between a perÂ and cytotoxicity and discuss various Ca2+ -mediated mechanisms that may contribute to the development of cell damage. turbation of intracellular Ca2+ homeostasis Ca2+ OVERLOAD AND CYTOTOXICITY The role of Ca2+ as an intracellular regulator of many physiological processes is well established. During the past several years, however, it has also become incre asingly clear that Ca2+ can play a determinant role in a variety of pathological conditions. Disruption of the mechanisms that regulate intraIpennanent address: Clinica Medica I, Universita di Pavia, 2To whom correspondence should be addressed Pavia, Italy 0362-1642/92/0415-0449$02. 00 NICOTERA, BELLOMO, & ORRENIUS cellular Ca2+ homeostasis is often an early event in the development of irreversible cell injury (7,8). There is convincing evidence that sustained increases in intracellular Ca2+ can activate cytotoxic mechanisms in various cells and tissues. For example, intracellular Ca2+ accumulation appears to mediate
Annual Review of Pharmacology and Toxicology – Annual Reviews
Published: Apr 1, 1992
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