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

FEBS Letters

Davis, Gregory¹  Nicotera, Pierluigi¹  Hartzell, Pia¹  Orrenius, Sten¹ 

[1] Department of Toxicology, Karolinska Institutet, Box 60400, S-104 01 Stockholm, Sweden

关键词: Cytosolic Ca2+Blebbing Proteolysis Hepatotoxicity;   

DOI  :  10.1016/0014-5793(86)81099-7

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

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.

【 授权许可】

Unknown