Leucine Acutely Reverses Burn-Induced Alterations in Translation Initiation in Heart

Abstract

Myocardial dysfunction is a common manifestation of thermal injury, the etiology of which appears to be multifactorial. We have previously demonstrated that burn injury impairs cardiac protein synthesis at the level of translation initiation. The purpose of the present study was to determine whether oral administration of leucine, which is known to stimulate translation initiation in skeletal muscle, can ameliorate burn-induced changes in signal transduction pathways known to regulate protein synthesis in cardiac muscle. To address this aim, thermal injury was produced by a 40% total body surface area full-thickness scald burn in anesthetized rats, and the animals were studied in the fasted condition 24 h later; appropriate time-matched nonburned control rats were also included. Separate groups of control and burn rats also received an oral gavage of leucine. To identify potential mechanisms responsible for regulating mRNA translation in cardiac muscle, several eukaryotic initiation factors (eIFs) were examined using immunoprecipitation and immunoblotting techniques. Hearts from burned rats demonstrated a redistribution of eIF4E as evidenced by the increased binding of the translational repressor 4E-BP1 with eIF4E, a decreased amount of eIF4E bound with eIF4G, and a decreased amount of the hyperphosphorylated gamma-isoform of 4E-BP1. Furthermore, constitutive phosphorylation of mTOR, the ribosomal protein S6, and eIF4G was also decreased in hearts from burned rats. In control rats, leucine failed to alter eIF4E distribution but did increase the phosphorylation of S6K1 and S6. However, in hearts from burn rats, leucine acutely reversed the alterations in eIF4E distribution as well as the changes in S6, eIF4G, and mTOR phosphorylation. These data suggest that oral administration of leucine can acutely reverse multiple defects in cardiac translation initiation produced by thermal injury.

Regulation of cardiac and skeletal muscle protein synthesis by individual branched-chain amino acids in neonatal pigs

“…†Mean differs from LD saline at P ϭ 0.11. mRNAs encode proteins involved in the protein synthetic machinery (17). Phosphorylation of S6K1 and rpS6 in the heart of mature rats has been reported to increase in response to oral administration of leucine that elevated plasma leucine to supraphysiological levels (24,25). However, the experimental conditions of the present study are substantially different from those in previous reports.…”

Essential Amino Acid Enriched High-Protein Enteral Nutrition Modulates Insulin-Like Growth Factor-1 System Function in a Rat Model of Trauma-Hemorrhagic Shock

“…Previous studies using a similar EAA formula or leucine alone to investigate the stimulatory effect upon skeletal muscle protein synthesis did not demonstrate changes in serum IGF-1 [20], [34], [35]. Despite various experimental conditions, those studies measured total IGF-1, instead of free levels.…”

Nutritional Supplements and Metabolic Syndrome

“…He did note, however, that a recent report indicates that under certain circumstances, such as severe burns, leucine stimulation can override down-regulation of mTOR 156 . He did note, however, that a recent report indicates that under certain circumstances, such as severe burns, leucine stimulation can override down-regulation of mTOR 156 .…”