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The Formation Of Plasma Membrane Blebs In Hepatocytes Exposed To Agents That Increase Cytosolic Ca2+ Is Mediated By The Activation Of A Non‐lysosomal Proteolytic System

P. Nicotera, P. Hartzell, G. Davis, S. Orrenius
Published 1986 · Biology, Medicine

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Exposure of isolated hepatocytes to extracellular ATP, cystamine or ionophore A23187 was associated with an increase in cytosolic Ca2+ concentration, a stimulation of intracellular proteolysis, and the appearance of plasma membrane blebs which preceded the loss of cell viability. Both bleb formation and cell killing were prevented when inhibitors of Ca2+‐activated neutral proteases, such as antipain or leupeptin, were included in the incubation medium, whereas inhibitors of lysosomal proteases had no effect. Thus, the activation of a Ca2+‐dependent, non‐lysosomal proteolytic system appears to be responsible for the plasma membrane blebbing and, ultimately, the cytotoxicity associated with treatment of hepatocytes with agents that disrupt intracellular Ca2+ homeostasis.
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