Caspase mRNA expression in a rat model of focal cerebral ischemia.
Proteins of the caspase family are involved in the signalling pathway that ultimately leads to programmed cell death (apoptosis), which has been reported to occur in some experimental models of stroke. In a previous paper we used quantitative reverse transcription and polymerase chain reaction (RT-PCR) to characterise changes in the mRNA expression of one member of this family, caspase-3, in a rat model of permanent focal ischemia. Here we have used this technique to study the expression of a further three caspases which are involved in different aspects of caspase signalling. Caspase-8, involved in Fas-mediated apoptosis, was upregulated in the cortex of ischemic rats. Caspase-11, which leads to the synthesis of the functional form of the cytokine interleukin-1 beta, also showed increased expression, but with a different temporal profile from caspase-8. In contrast, caspase-9, which forms part of the pathway signalling through the mitochondria, showed a decrease in expression. The expression of a further four caspases (1, 2, 6 and 7) has also been characterised in a simpler experiment. These caspases all showed distinctive patterns of expression following the induction of ischemia. These data lead us to conclude that caspase expression as a whole is under very strict transcriptional control in this model. Certain elements of caspase signalling, such as the Fas-induced pathway and the events upstream of IL-1 beta processing, are upregulated, while others are not. This may be due to some form of genetic program activated in response to ischemia in the brain and may highlight which biological pathways are modulated.
Harrison
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DC
Department of Neurology, GlaxoSmithKline, New Frontiers Science Park, Third Avenue, Harlow, Essex CM19 5AW, UK. david_c_harrison@sbphrd.com
Davis
R P
RP
Bond
B C
BC
Campbell
C A
CA
James
M F
MF
Parsons
A A
AA
Philpott
K L
KL
D000818:Animals; D017209:Apoptosis / Q000502:physiology; D001921:Brain / Q000098:blood supply / Q000201:enzymology*; D002545:Brain Ischemia / Q000378:metabolism*; D020170:Caspase 1 / Q000235:genetics; D053143:Caspase 2; D053148:Caspase 3; D053178:Caspase 6; D053179:Caspase 7; D053181:Caspase 8; D053453:Caspase 9; D020169:Caspases / Q000235:genetics*; D015971:Gene Expression Regulation, Enzymologic; D020244:Infarction, Middle Cerebral Artery / Q000378:metabolism*; D008297:Male; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
D012333:RNA, Messenger; C505410:Casp3 protein, rat; C491071:Casp4 protein, rat; C505518:Casp6 protein, rat; C505528:Casp8 protein, rat; C506435:Casp9 protein, rat; D053143:Caspase 2; D053148:Caspase 3; D053178:Caspase 6; D053179:Caspase 7; D053181:Caspase 8; D053453:Caspase 9; D020169:Caspases; D020170:Caspase 1