An indirect method demonstrating that CCl4-dependent hepatocyte injury is linked to a rise in intracellular calcium ion concentration.
The capacity of CCl4 to activate phospholipase A2 (PLA2) of isolated hepatocytes in suspension, and the toxicity of CCl4 against such hepatocytes, was confirmed. It was shown that these actions of CCl4 are independent of the concentration of Ca2+ ions in the suspension medium over a 25,000-fold range. In particular, toxicity of CCl4 does not require high Ca2+ in the suspension medium. The Ca(2+)-ionophore A23187 can also activate PLA2, and it also is toxic. However, in this case activation of PLA2 and toxicity require a high medium Ca2+ ion concentration. These radically different modes of action of CCl4 and A23187 permitted an indirect confirmation of the hypothesis that the activation of PLA2 by CCl4, and the toxicity of CCl4 depend on CCl4-dependent mobilization of intracellular stores of Ca2+, and a rise in the concentration of Ca2+ ions in the hepatocyte cytosol.
Glende
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Department of Physiology & Biophysics, School of Medicine, Case Western Reserve University, Cleveland, OH 44106.
Recknagel
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D000818:Animals; D002118:Calcium / Q000032:analysis*; D002251:Carbon Tetrachloride / Q000633:toxicity*; D002478:Cells, Cultured; D003600:Cytosol / Q000737:chemistry; D004789:Enzyme Activation; D019856:Ethanolamine; D004983:Ethanolamines / Q000032:analysis; D066298:In Vitro Techniques; D007770:L-Lactate Dehydrogenase / Q000032:analysis; D008099:Liver / Q000737:chemistry / Q000187:drug effects*; D008297:Male; D010741:Phospholipases A / Q000378:metabolism; D054467:Phospholipases A2; D051381:Rats; D011919:Rats, Inbred Strains
D004983:Ethanolamines; D019856:Ethanolamine; D002251:Carbon Tetrachloride; D007770:L-Lactate Dehydrogenase; D010741:Phospholipases A; D054467:Phospholipases A2; D002118:Calcium