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Amino acids‐induced cardiac protection by promoting mitochondrial function via mTOR and Opa‐1 signaling
Author(s) -
Morio Atsushi,
Satomi Shiho,
Toyota Yukari,
Watanabe Tomoyuki,
Tsutsumi Yasuo M
Publication year - 2020
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.2020.34.s1.07422
Subject(s) - pi3k/akt/mtor pathway , myocyte , mitochondrial fusion , mitochondrion , protein kinase b , chemistry , amino acid , microbiology and biotechnology , signal transduction , medicine , pharmacology , biology , biochemistry , mitochondrial dna , gene
Objects Amino acids, especially branched chain amino acids (BCAAs), have important regulatory roles in protein synthesis. Recently studies revealed that BCAAs protect against ischemia/reperfusion (I/R) injury. We studied the signaling pathway and mitochondrial function affecting a cardiac preconditioning of BCAAs. Methods Cardiac myocytes were isolated by cardiac retrograde aortic perfusion and collagenase and were subjected to simulated ischemia and cell death was quantified. Immunoblot and real time PCR were performed as biochemical assay and mitochondrial function was assessed using Seahorse XF cell Mito test. Results In myocytes undergoing simulated I/R, BCAA treatment significantly preserved cell viability (71.7 ± 2.7% vs. 34.5 ± 1.6%, respectively, p < 0.0001), whereas rapamycin prevented this BCAA‐induced cardioprotective effect (43.5 ± 3.4% vs. BCAA, p < 0.0001). To elucidate the mechanism, we assessed changes in the mitochondrial fusion regulators Opa‐1, Mfn‐1, and Mfn‐2. BCAA treatment increased expression of Opa‐1, but not Mfn‐1 or Mfn‐2. Enhanced mitochondrial fusion also improved mitochondrial function including oxygen consumption rate. Conclusions BCAA acutely regulates mitochondrial metabolism in cardiomyocytes and increased mitochondrial fusion, Opa‐1, and the Akt‐mTOR pathway, offering a novel target for prevention and treatment of coronary disease. Support or Funding Information This study was supported by Japan Society of Promotion Science #19K09353 to YMT.