Nedreglering av proteinsyntes och anabol signalering av alkohol

[King Grub]

Alcohol (EtOH) decreases protein synthesis, mTOR-mediated signaling and blunts the anabolic response to growth factors in skeletal muscle. The purpose of the current investigation was to determine whether acute alcohol intoxication antagonizes the contraction-induced increase in protein synthesis and mTOR signaling in skeletal muscle. Fasted male mice were injected IP with 3 g/kg EtOH or saline (Control), and the right hindlimb was electrically stimulated (10 sets of 6 contractions). The gastrocnemius muscle complex was collected 30 min, 4 h or 12 h after stimulation. EtOH decreased in vivo basal protein synthesis (PS) in the non-stimulated muscle compared with time-matched Controls at 30 min, 4 h and 12 h. In Control, but not EtOH, PS was decreased 15% after 30 min. In contrast, PS was increased in Control 4 h post-stimulation but remained unchanged in EtOH. Lastly, stimulation increased PS 10% in Control and EtOH at 12 h, even though the absolute rate remained reduced by EtOH. The stimulation-induced increase in the phosphorylation of S6K1 Thr421/Ser424 (20-52%), S6K1 Thr389 (45-57%) and its substrate, rpS6 Ser240/244 (37-72%) was blunted by EtOH at 30 min, 4 h and 12 h. Phosphorylation of 4E-BP1 Ser65 was also attenuated by EtOH (61%) at 4 h. Conversely, phosphorylation of ERK Thr202/Tyr204 was increased by stimulation in Control and EtOH mice at 30 min, but only in Control at 4 h. Our data indicate acute alcohol intoxication suppresses muscle protein synthesis for at least 12 h and greatly impairs contraction-induced changes in synthesis and mTOR signaling.

Alcohol impairs skeletal muscle protein synthesis and mTOR signaling in a time-dependent manner following electrically stimulated muscle contraction. Journal of Applied Physiology 25 September 2014Vol. no. , DOI: 10.1152/japplphysiol.00180.2014.

http://jap.physiology.org/content/early/2014/09/23/japplphysiol.00180.2014.full-text.pdf%2Bhtml