Overexpression of the elongation factor 1A1 relates to muscle proteolysis and proapoptotic p66(ShcA) gene transcription in hypercatabolic trauma patients.

Abstract

The eukaryotic elongation factors (eEF1A2 and eEF1A1) play a key role in translation of messenger RNA (mRNA) to protein. In skeletal muscle of healthy humans, EEF1A2 is overexpressed and selected over EEF1A1. In cellular stress models, muscle EEF1A1 expression increased and was associated with apoptosis and catabolism. We have determined mRNA levels of EEF1A1 and EEF1A2, as well as those of other proapoptotic genes, such as p66(ShcA) and c-MYC, in skeletal muscle of severely traumatized patients and healthy volunteers. Muscle protein kinetic was determined by stable isotopes and the arteriovenous technique. The patients were in a hypercatabolic condition because the rate of muscle proteolysis exceeded that of synthesis. Mean mRNA levels of EEF1A1 and EEF1A2 were 165- and 29-fold greater (P < .01) in patients than in the control group, respectively. Mean p66(ShcA) mRNA levels were 3-fold greater (P < .05) in patients than in the controls. In contrast, c-MYC mRNA levels were not significantly different in patients and healthy controls. In patients, muscle mRNA levels of EEF1A1 and p66(ShcA) directly correlated (P < .05) with the rate of proteolysis (R = 0.901 and R = 0.826, respectively). This is in agreement with a reduction in actin and tubulin protein content, both markers of cytoskeletal and sarcomeric disorganization, and with an increased poly(adenosine diphosphate-ribose) polymerase cleavage, a marker of apoptosis. In conclusion, in hypercatabolic traumatized patients, an up-regulation of muscle EEF1A1 and p66(ShcA) relates to proteolysis rate, suggesting an involvement of these genes in muscle catabolic response.