Thiopental and isoflurane attenuate the decrease in hippocampal phosphorylated Focal Adhesion Kinase (pp125FAK) content induced by oxygen-glucose deprivation.
Br J Anaesth
; 93(2): 270-4, 2004 Aug.
Article
in En
| MEDLINE
| ID: mdl-15194624
ABSTRACT
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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Collection:
01-internacional
Database:
MEDLINE
Main subject:
Thiopental
/
Protein-Tyrosine Kinases
/
Anesthetics, Intravenous
/
Anesthetics, Inhalation
/
Isoflurane
Limits:
Animals
Language:
En
Journal:
Br J Anaesth
Year:
2004
Document type:
Article
Affiliation country:
France