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Thiopental and isoflurane attenuate the decrease in hippocampal phosphorylated Focal Adhesion Kinase (pp125FAK) content induced by oxygen-glucose deprivation.

Authors: Dahmani, S  Tesniere, A  Rouelle, D  Desmonts, JM  Mantz, J 
Citation: Dahmani S, etal., Br J Anaesth. 2004 Aug;93(2):270-4. Epub 2004 Jun 11.
Pubmed: (View Article at PubMed) PMID:15194624
DOI: Full-text: DOI:10.1093/bja/aeh188

BACKGROUND: Thiopental and isoflurane exhibit neuroprotective effects against cerebral ischaemia. Here, we hypothesized that oxygen-glucose deprivation decreases the ATP-dependent phosphorylation process of Focal Adhesion Kinase (pp125FAK, a functionally important non-receptor tyrosine kinase), and that this phenomenon is attenuated by thiopental and isoflurane. METHODS: Rathippocampal slices were subjected to an anoxic-aglycaemic (or physiologic, control) challenge followed by 3-h reperfusion, and treated with various concentrations of thiopental and isoflurane. PP125FAK phosphorylation was measured by immunoblotting. Neuronal death was assessed by immunostaining with bis-benzimide. RESULTS: Significant neuronal death was detected after 30 min (but not 10) of anoxia-aglycaemia (40 (4) vs 14 (5)% of control, P<0.05). At 30 min, phosphorylated pp125FAK content was significantly decreased by anoxic glucose-free conditions (55 (27)% of control, P<0.05). This effect was markedly attenuated by thiopental (10 and 100 microM) and isoflurane (1 and 2%). Under control conditions, thiopental (1, 10, and 100 microM) and isoflurane (0.5, 1, and 2%) increased pp125FAK phosphorylation in a concentration-related fashion. This effect was blocked by chelerythrin and bisindolylmaleimide I and IX (10 microM, three structurally distinct inhibitors of protein kinase C, PKC) but not the N-methyl-D-aspartate (NMDA) receptor antagonist MK801 (10 microM). CONCLUSION: Phosphorylated pp125FAK content was markedly decreased in hippocampal slices subjected to oxygen-glucose deprivation. Thiopental and isoflurane significantly attenuated this phenomenon, possibly via PKC activation.

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CRRD Object Information
CRRD ID: 2292607
Created: 2008-04-25
Species: All species
Last Modified: 2008-04-25
Status: ACTIVE



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RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.