Chronic Alcohol Feeding Impairs mTOR(Ser²⁴⁴⁸) Phosphorylation in Rat Hearts

Abstract

Chronic ethanol consumption does not alter the distribution of mTOR between TORC1 and TORC2, but instead diminishes mTOR phosphorylation on Ser(2448) independent of changes in tumor suppressor complex 2 and PKB phosphorylation. Furthermore, the data suggest that protein synthesis in rats fed a diet containing ethanol is limited by mTOR-dependent reduction in phosphorylation of S6K1(Thr(389)) and eIF4G(Ser(1108)) secondary to reduced phosphorylation of mTOR(Ser(2448)).

Chronic alcohol consumption disrupts myocardial protein balance and function in aged, but not adult, female F344 rats

“…This alcohol-induced decrement is in part mTOR-dependent as demonstrated by the reduced phosphorylation of mTOR, S6K1, S6, eIF4G, and 4E-BP1, the latter of which is responsible for the observed reduction in the assembly of the active eIF4E·eIF4G capbinding complex (72,73,77). These protein metabolic effects are also associated with a cardiac dysfunction after longer periods of alcohol consumption (14,35,64,66).…”

“…Multiple lines of evidence indicate alcohol consumption for a period of ϳ12-24 wk in male rats reduces myocardial protein synthesis (15,61,69,72,73,75,77). This alcohol-induced decrement is in part mTOR-dependent as demonstrated by the reduced phosphorylation of mTOR, S6K1, S6, eIF4G, and 4E-BP1, the latter of which is responsible for the observed reduction in the assembly of the active eIF4E·eIF4G capbinding complex (72,73,77).…”

“…Consumption of the liquid diet was assessed daily and animals were weighed weekly. This duration of alcohol feeding leads to skeletal muscle wasting and alterations in muscle protein balance in both male and female rats (15,61,72,73,77). All experiments described herein were approved by the Institutional Animal Care and Use Committee of the Pennsylvania State University and adhered to the National Institutes of Health (NIH) guidelines for the use of experimental animals.…”

“…All plasma and heart samples were stored at Ϫ80°C until analyzed. Frozen muscle was powdered under liquid nitrogen and the rate of incorporation of [ 3 H]Phe into myofibrillar and sarcoplasmic proteins determined as previously described (41,42,72,73,78).…”

Functional proteomic analysis reveals sex-dependent differences in structural and energy-producing myocardial proteins in rat model of alcoholic cardiomyopathy

“…The degree of cardiac dysfunction is proportional to the duration and severity of alcohol consumption (38). The functional and structural changes observed with the progression of the disease to a dilated heart are consistent with alterations in steps in protein synthesis inhibition that have been implicated in messenger RNA selection for translation (10,20,41,45). Therefore it seems reasonable that the expression of specific proteins may be affected.…”