title: Bid is cleaved by calpain to an active fragment in vitro and during myocardial ischemia/reperfusion.
abstract: Reperfusion after myocardial ischemia is associated with a rapid influx of calcium, leading to activation of various enzymes including calpain. Isolated perfused adult rabbit hearts subjected to global ischemia and reperfusion were studied. Calpain or a calpain-like activity was activated within 15 min after reperfusion, and preconditioning suppressed calpain activation. In contrast, caspase activation was not detected although cytochrome c was released after ischemia and reperfusion. The pro-apoptotic BH3-only Bcl-2 family member, Bid, was cleaved during ischemia/reperfusion in the adult rabbit heart. Recombinant Bid was cleaved by calpain to a fragment that was able to mediate cytochrome c release. The calpain cleavage site was mapped to a region within Bid that is extremely susceptible to proteolysis. These findings suggest that there is cross-talk between apoptotic and necrotic pathways in myocardial ischemia/reperfusion injury.
authors.affiliation: Scripps Research Institute and the Burnham Institute, La Jolla, California 92037, USA.
authors.forename: M
authors.initials: M
authors.lastname: Chen
authors.forename: H
authors.initials: H
authors.lastname: He
authors.forename: S
authors.initials: S
authors.lastname: Zhan
authors.forename: S
authors.initials: S
authors.lastname: Krajewski
authors.forename: J C
authors.initials: JC
authors.lastname: Reed
authors.forename: R A
authors.initials: RA
authors.lastname: Gottlieb
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D051023:BH3 Interacting Domain Death Agonist Protein; D002154:Calpain / Q000378:metabolism*; D002352:Carrier Proteins / Q000378:metabolism*; D008297:Male; D008969:Molecular Sequence Data; D017202:Myocardial Ischemia / Q000378:metabolism*; D015428:Myocardial Reperfusion Injury / Q000378:metabolism*; D009206:Myocardium / Q000378:metabolism*; D011817:Rabbits; D011994:Recombinant Proteins / Q000378:metabolism
chemical_list: D051023:BH3 Interacting Domain Death Agonist Protein; D002352:Carrier Proteins; D011994:Recombinant Proteins; D002154:Calpain