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 repor ted to occur in some experimental models of stroke. In a previous paper we used quantitative reverse transcription and polymerase chain reaction (RT-P CR) to characterise changes in the mRNA expression of one member of this fa mily, caspase-3. in a rat model of permanent focal ischemia. Here we have u sed this technique to study the expression of a further three caspases whic h are involved in different aspects of caspase signalling. Caspase-8, invol ved in Fas-mediated apoptosis, was upregulated in the cortex of ischemic ra ts. Caspase-11, which leads to the synthesis of the functional form of the cytokine interleukin-1 beta. also showed increased expression, but with a d ifferent temporal profile From caspase-8. In contrast, caspase-9, which for ms part of the pathway signalling through the mitochondria. showed a decrea se 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 sh owed distinctive patterns of expression following the induction of ischemia . These data lead us to conclude that caspase expression as a whole is unde r very strict transcriptional control in this model. Certain elements of ca spase signalling, such as the Fas-induced pathway and the events upstream o f 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 th e brain and may highlight which biological pathways are modulated. (C) 2001 Elsevier Science B.V. All rights reserved.