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Original

Sphingomyelinase-induced ceramide production stimulate calcium-independent JNK and PP2A activation following cerebral ischemia

, , , &
Pages 1073-1080 | Received 06 Apr 2009, Accepted 29 Sep 2009, Published online: 05 Nov 2009
 

Abstract

Primary objective: Intracellular calcium overload is considered to be a key pathologic factor for ischemic stroke; however, there are other signal molecules produced in response to ischemic stimuli. The present study investigated the ceramide signal pathway, which is associated with cerebral ischemia in a calcium-independent manner.

Methods: Male Sprague-Dawley rats were subjected to 10-minute four-vessel occlusion. Ketamine, a blocker of calcium-ion channels, or TPCK or fumonisin B1, inhibitors of ceramide production in the sphingomyelinase and de novo pathways, respectively, were administrated to the rats prior to inducing ischemia. Ceramide levels were determined by immunofluorescence, protein activity was assessed by immunoblotting and PP2A activity was measured using a protein phosphatase assay system.

Results: The morphologic data indicated that ischemia-induced ceramide production was largely restricted to glia cells in the rat hippocampus. TPCK, but not ketamine or fumonisin B1, blocked the ceramide pathway and its downstream molecules, JNK and PP2A.

Conclusions: Cerebral ischemia up-regulates the sphingomyelin–ceramide pathway, which involves calcium-independent JNK and PP2A activation in hippocampal glia; this may play a significant role in cerebral lesions post-ischemia.

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