Dissociation Between Acute Alcohol (EtOH) Intoxication‐Induced Increases in Atrogin‐1 and MuRF1 mRNA and Rates of Proteolysis in Skeletal Muscle

Abstract

EtOH abuse causes skeletal muscle wasting resulting, in part, from a reduction in protein synthesis. However, whether alcohol enhances muscle proteolysis remains controversial. The current study determined whether acute EtOH stimulated muscle protein breakdown by measuring the mRNA content for the muscle‐specific ubiquitin E3 ligases atrogin‐1 and MuRF1 (aka atrogenes) and assessing the in vitro rate of proteolysis. IP injection of EtOH in rats increased atrogene mRNA in a time‐dependent manner, peaking at 8 h (4‐fold) and returning to baseline by 24 h. The EtOH‐induced rise in atrogenes was dose‐dependent, with increases observed in rats with blood alcohol levels >150 mg/dL. In contrast, there was no EtOH‐induced change in atrogene mRNA in heart or soleus under these conditions. Elevated atrogene expression appears mediated indirectly because neither perfusion of an EtOH‐containing buffer into the isolated hindlimb of control rats nor incubation of C2C12 myocytes with EtOH increased atrogene mRNA. Finally, IP injection of a maximally effective dose of EtOH showed no change in proteolysis determined in the isolated epitrochlearis muscle. These data demonstrate EtOH selectively increases atrogene mRNA in fast‐twitch skeletal muscle, most likely via production of a secondary mediator, but this change was not associated with a concomitant stimulation of muscle protein breakdown. (AA11290 and AA12814).