Head-down tilt increases rat cardiac muscle eIF-2 alpha phosphorylation

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Abstract
We previously demonstrated that head-down tilt in rats decreases heart polypeptide initiation rate and proposed a mechanism whereby redistribution of the chaperone heat-shock cognate/heat-shock protein-70 (HSC/HSP-70) facilitates the phosphorylation of eukaryotic initiation factor-2 alpha (eIF-2 alpha). In this study, two-dimensional gel electrophoretic analysis of eIF-2 alpha showed no phosphorylation in control hearts. At 8 h of head-down tilt, there was a 45% increase in total eIF-2 alpha, and 79% was phosphorylated. At 18 h, eIF-2 alpha increased to 142% of control, of which 4% was phosphorylated. This is consistent with the previous study where, at 8 h, there was a 78% increase in polysomal HSC/HSP-70 and a shift in the polysome center-of-mass to lighter polysomes (indicating decreased initiation). After 18 h of suspension, polysomal HSC/HSP-70 levels were 24% relative to control, and the center-of-mass returned toward control. We conclude that the decrease in polypeptide initiation during head-down tilt is mediated by HSC/HSP-70 via phosphorylation of eIF-2 alpha.

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