The role of calpain in oncotic cell death.

Abstract:

:Numerous lines of evidence demonstrate that calpains, a family of 14 Ca(2+)-activated neutral cysteine proteases, are involved in oncotic cell death in a variety of models. At this time, the biochemistry of most calpains and the specific roles of different calpains in physiology and pathology remain to be determined. A number of calpain substrates have been identified in cellular systems, including cytoskeletal proteins, and recent studies suggest that calpains mediate the increase in plasma membrane permeability to ions and the progressive breakdown of the plasma membrane observed in oncosis through the proteolysis of cystokeletal and plasma membrane proteins. Further, a number of reports provide evidence that the mitochondrial dysfunction observed in oncosis may be mediated by a mitochondrial calpain of unknown identity. Finally, a number of diverse calpain inhibitors have been developed that show cytoprotective properties in cellular systems and in vivo following diverse insults. It is suggested that future research be directed toward elucidation of the role(s) of specific calpain isozymes in physiological and pathological conditions; identifying and linking specific calpain substrates with altered cellular functions; and developing cell-permeable, potent, isozyme-selective calpain inhibitors.

authors

Liu X,Van Vleet T,Schnellmann RG

doi

10.1146/annurev.pharmtox.44.101802.121804

keywords:

subject

Has Abstract

pub_date

2004-01-01 00:00:00

pages

349-70

eissn

0362-1642

issn

1545-4304

journal_volume

44

pub_type

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