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Protective effects of amino acids on the ischemic myocardium via mTOR/S6 kinase pathway
Author(s) -
Tsutsumi Yasuo M,
Tanaka Katsuya,
Kasai Asuka,
Kadota Naoko,
Oshita Shuzo
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.852.3
Subject(s) - amino acid , pi3k/akt/mtor pathway , ischemia , chemistry , activator (genetics) , leucine , catabolism , phosphorylation , pharmacology , protein biosynthesis , kinase , biochemistry , medicine , metabolism , apoptosis , receptor
Leucine, as an essential amino acids and activator of mammalian target of rapamycin (mTOR), promotes protein synthesis and suppresses protein catabolism. Recent studies have showed that the mTOR/p70S6K complex may mediate the beneficial effects to ischemia‐reperfusion injury. We therefore proposed that amino acids may produce cardiac protection against myocardial ischemia‐reperfusion mediated by mTOR/p70S6K. Mice were subjected to 30 min of myocardial ischemia followed by 120 min of reperfusion. Control mice were exposed to ischemia and reperfusion only. Some mice were randomly assigned to receive amino acids, administered after ischemia and/or rapamycin, mTOR inhibitor, were given 15 min prior to amino acids postconditioned. Amino acids postconditioned mice were significantly reduced infarct size compared to control group (16 ± 3% vs. 43 ± 4% [n = 6] respectively, p<0.05) and rapamycin eliminated the protection produced by amino acids (45 ± 4% [n = 4]). Additionally, the hearts treated with amino acids had a 2.5‐fold increase in phosphorylation of both mTOR and p70S6K, and pretreated with rapamycin completely abolished mTOR/p70S6K phosphorylations in response to amino acids treatment. These results indicate that amino acids induced myocardial protection involves activation of the p70S6K that is mediated by the mTOR.