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.
journal_name
Annu Rev Pharmacol Toxicoljournal_title
Annual review of pharmacology and toxicologyauthors
Liu X,Van Vleet T,Schnellmann RGdoi
10.1146/annurev.pharmtox.44.101802.121804keywords:
subject
Has Abstractpub_date
2004-01-01 00:00:00pages
349-70eissn
0362-1642issn
1545-4304journal_volume
44pub_type
杂志文章,评审abstract::Microbicides, substances applied topically to prevent sexual HIV infection, are needed to empower receptive sexual partners with effective prevention methods. Several large microbicide trials, however, failed to demonstrate efficacy, thus motivating a reevaluation of the current microbicide development paradigm, which...
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pub_type:
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更新日期:2003-01-01 00:00:00
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