Alkylating Toxins and the Liver Plasma Membrane Calcium Pump/Calcium ATPase
The role of altered calcium homeostasis as a possible unifying mechanism of acute lethal cell injury by chemical toxins, ischemia, and other agents has attracted much interest (Trump and Berezesky, 1984; Schanne et al., 1979; Jewell et al., 1982; Lowrey et al., 1981; Bellomo and Orrenius, 1985). Clearly, many cellular processes are regulated or influenced by the cytosolic free calcium concentration, which in turn is controlled by calcium transport systems of the plasma membrane, the endoplasmic reticulum, and the mitochondria. Moore and coworkers (1976) first showed over 10 years ago that liver microsomes isolated 30 or more minutes after administration of CC14 to Sprague-Dawley rats had virtually lost the capacity for ATP-dependent Ca2+ uptake. They postulated that inhibition of the liver endoplasmic reticulum Ca2+ pump might be the initial insult disrupting Ca2+ homeostasis sufficiently to produce an injury allowing massive Ca2+ influx into the cell (Moore et al., 1976).
KeywordsLiver Plasma Membrane Plasma Membrane Vesicle Lipid Oxidation Product Cytosolic Free Calcium Concentration Altered Calcium Homeostasis
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