Double-stranded RNA-dependent protein kinase activation modulates endotoxin-induced XXXX .

@entity4589 @entity52768 @entity13129 @entity19 @entity425 @entity4699
Diaphragm @entity4699 activation plays a key role in modulating sepsis-induced @entity4589 . It is also known that double-stranded RNA-dependent protein kinase ( @entity52768 ) is a regulator of @entity4699 activation in neural tissue. We tested the hypothesis that the @entity52768 pathway modulates sepsis-induced diaphragmatic @entity4699 activation. We first evaluated the time course of diaphragm @entity52768 activation following endotoxin administration in @entity19 . We then determined whether administration of a @entity52768 inhibitor ( @entity13129 ) prevents endotoxin-induced diaphragm @entity4699 activation and contractile dysfunction in @entity19 . Finally, we investigated if inhibition of @entity52768 (using either @entity13129 or transfection with dominant-negative @entity52768 ) blocks @entity4699 activation in cytokine treated C   C       cells. Endotoxin markedly activated diaphragm @entity52768 (with increases in both active phospho- @entity52768 protein levels, P < 0.03, and directly measured @entity52768 activity, P < 0.01) and increased active @entity4699 levels (P < 0.01). Inhibition of @entity52768 with @entity13129 prevented endotoxin-induced diaphragm @entity4699 activation (P < 0.01) and @entity425 (P < 0.001). Inhibition of @entity52768 with either @entity13129 or transfection with dominant-negative @entity52768 blocked @entity4699 activation in isolated cytokine-treated C   C       cells. These data implicate @entity52768 activation as a major factor mediating cytokine-induced skeletal muscle @entity4699 activation and @entity425 .
