Regulation of XIAP and Smac/DIABLO in the rat hippocampus following transient forebrain ischemia.
We investigated the expression of XIAP (X chromosome-linked inhibitor of apoptosis protein) and Smac/DIABLO, a newly identified mitochondrial apoptogenig molecule in the hippocampus following transient global ischemia. Transient global ischemia produced by two-vessel occlusion triggers the delayed neuronal death of CA1 neurons in the hippocampus. We demonstrate that CA1 neuronal loss induced by ischemia (10 min) is preceded by a selective and marked elevation of catalytically active caspase-3 in these neurons, indicative of apoptosis. XIAP (X chromosome-linked inhibitor of apoptosis protein) is a member of the inhibitor of apoptosis (IAP) gene family that, in addition to suppressing cell death by inhibition of caspases, is involved in an increasing number of signalling cascades. The present study shows alterations in the levels of XIAP and of Smac/DIABLO (second mitochondrial activator of caspase) after cerebral ischemia. The protein levels of XIAP and the number of XIAP-positive cells were regulated by cerebral ischemia in a strictly time and region dependent manner. The largest change in XIAP-IR was observed in the CA1 sub field, which is the most vulnerable area of hippocampus. The mitochondrial expression level of Smac/DIABLO increased during reperfusion. Smac/DIABLO expression was associated with alteration of the XIAP levels and the appearance of activated form of caspase-3 within the hippocampus during reperfusion in spatial and temporal manners.
Siegelin
M D
MD
Institute of Anatomy III, Dr. Senckenbergische Anatomie, Clinic of the JWG-University, Theodor-Stern-Kai 7, Frankfurt/Main 60590, Germany.
Kossatz
L S
LS
Winckler
J
J
Rami
A
A
D000818:Animals; D017209:Apoptosis / Q000502:physiology; D015153:Blotting, Western; D002352:Carrier Proteins / Q000378:metabolism; D053148:Caspase 3; D053453:Caspase 9; D020169:Caspases / Q000378:metabolism; D015938:Complement Membrane Attack Complex; D003165:Complement System Proteins; D004789:Enzyme Activation / Q000502:physiology; D006023:Glycoproteins / Q000378:metabolism*; D006624:Hippocampus / Q000378:metabolism*; D007150:Immunohistochemistry; D051034:Inhibitor of Apoptosis Proteins; D002546:Ischemic Attack, Transient / Q000378:metabolism*; D008297:Male; D008840:Microfilament Proteins / Q000378:metabolism; D008928:Mitochondria / Q000201:enzymology / Q000378:metabolism; D009474:Neurons / Q000473:pathology; D016548:Prosencephalon / Q000378:metabolism*; D011506:Proteins / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D013347:Subcellular Fractions / Q000378:metabolism; D051636:X-Linked Inhibitor of Apoptosis Protein; D013049:Spectrin
D002352:Carrier Proteins; D053148:Caspase 3; D053453:Caspase 9; D020169:Caspases; D015938:Complement Membrane Attack Complex; D003165:Complement System Proteins; D006023:Glycoproteins; D051034:Inhibitor of Apoptosis Proteins; D008840:Microfilament Proteins; D011506:Proteins; D051636:X-Linked Inhibitor of Apoptosis Protein; D013049:Spectrin; C047610:SC5b-9 protein complex; C494837:Xiap protein, rat; C505410:Casp3 protein, rat; C506435:Casp9 protein, rat