Regulation of caspases and XIAP in the brain after asphyxial cardiac arrest in rats.
The aim of this study was to determine whether hypoxic-ischemia from asphyxial cardiac arrest activates brain caspases-1 and -3, and the anti-apoptotic protein, XIAP. Asphyxial cardiac arrest in rats was used to induce hypoxic-ischemia. A pan-caspase inhibitor (zVAD) was given in the treatment group. At 72 h after reperfusion, caspase-3 and XIAP expression were present in multiple vulnerable brain regions, whereas caspase-1 was predominantly found in the CA1 hippocampus. zVAD significantly reduced expression of caspases and XIAP and the number of ischemic neurons in the CA1 hippocampus while neurological deficit scores were improved. We conclude that hypoxic-ischemia increases caspases-1 and-3, and XIAP expression. Treatment with zVAD significantly decreases caspase and XIAP expression in these brain regions and improves neurological outcome.
Katz
L M
LM
Department of Emergency Medicine, University of North Carolina at Chapel Hill, Neurosciences Hospital, Chapel Hill, NC 27599, USA.
Lotocki
G
G
Wang
Y
Y
Kraydieh
S
S
Dietrich
W D
WD
Keane
R W
RW
D000590:Amino Acid Chloromethyl Ketones / Q000494:pharmacology; D000818:Animals; D001237:Asphyxia / Q000150:complications*; D001921:Brain / Q000187:drug effects / Q000201:enzymology* / Q000473:pathology; D020170:Caspase 1 / Q000378:metabolism; D053148:Caspase 3; D061945:Caspase Inhibitors; D020169:Caspases / Q000378:metabolism*; D016923:Cell Death / Q000187:drug effects / Q000502:physiology*; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology; D015536:Down-Regulation / Q000187:drug effects / Q000502:physiology; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects / Q000502:physiology; D006323:Heart Arrest / Q000150:complications*; D006624:Hippocampus / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D020925:Hypoxia-Ischemia, Brain / Q000188:drug therapy / Q000201:enzymology* / Q000209:etiology; D007150:Immunohistochemistry; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D011506:Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D051636:X-Linked Inhibitor of Apoptosis Protein
D000590:Amino Acid Chloromethyl Ketones; D061945:Caspase Inhibitors; D015853:Cysteine Proteinase Inhibitors; D011506:Proteins; D051636:X-Linked Inhibitor of Apoptosis Protein; C096713:benzyloxycarbonylvalyl-alanyl-aspartyl fluoromethyl ketone; C505410:Casp3 protein, rat; D053148:Caspase 3; D020169:Caspases; D020170:Caspase 1