Synergetic effects of caspase 3 and mu-calpain in XIAP-breakdown upon focal cerebral ischemia.
Dysregulation of apoptosis is involved in a wide spectrum of disease ranging from proliferative to neurodegenerative disorders. The recently discovered X-linked inhibitor of apoptosis protein (XIAP) is among the most potent inhibitors of apoptosis. This protein binds to and inhibits both initiator caspases and effector caspases such as caspase-3. The aim of this study was to investigate the relationships between XIAP-breakdown, caspase activation in the development of delayed infarct upon ischemia. We demonstrated that endogenous XIAP is cleaved at least into two fragments during reperfusion following the ischemic insult. The two fragments produced seem to be related to caspase-3 and mu-calpain activities, which are massively enhanced in tissues challenged by ischemia. Therefore, degradation of XIAP by mu-calpain in our system may decrease the activation threshold of caspase-3 normally held in check by the IAPs and/or lead to auto-activation of other caspases.
Rami
Abdelhaq
A
Institute of Cellular and Molecular Anatomy, Dr. Senckenbergische Anatomie, Johann Wolfgang Goethe-University, Theodor-Stern-Kai 7, 60590, Frankfurt/Main, Germany. Rami@em.uni-frankfurt.de
Agarwal
Rachna
R
Spahn
Alexander
A
D000818:Animals; D017209:Apoptosis / Q000502:physiology; D015153:Blotting, Western; D002154:Calpain / Q000378:metabolism*; D053148:Caspase 3 / Q000378:metabolism*; D007150:Immunohistochemistry; D020244:Infarction, Middle Cerebral Artery / Q000473:pathology; D002546:Ischemic Attack, Transient / Q000378:metabolism*; D017078:Laser-Doppler Flowmetry; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D014404:Tubulin / Q000378:metabolism; D051636:X-Linked Inhibitor of Apoptosis Protein / Q000378:metabolism*
D014404:Tubulin; D051636:X-Linked Inhibitor of Apoptosis Protein; D002154:Calpain; D053148:Caspase 3; C449002:mu-calpain