title: BCKA down-regulates mTORC2-Akt signal and enhances apoptosis susceptibility in cardiomyocytes.
abstract: Diabetic mellitus (DM) portends poor prognosis concerning pressure overloaded heart disease. Branched-chain amino acids (BCAAs), elements of essential amino acids, have been found altered in its catabolism in diabetes decades ago. However, the relationship between BCAAs and DM induced deterioration of pressure overloaded heart disease remains controversial. This study is aimed to investigate the particular effect of BCKA, a metabolite of BCAA, on myocardial injury induced by pressure overloaded. Primary cardiomyocytes were incubated with or without BCKA and followed by treatment with isoproterenol (ISO); then cell viability was detected by CCK8 and apoptosis was examined by TUNNEL stain and caspase-3 activity analysis. Compared to non-BCKA incubated group, BCKA incubation decreased cell survival and increased apoptosis concentration dependently. Furthermore, Western blot assay showed that mTORC2-Akt pathway was significantly inactivated by BCKA incubation. Moreover, overexpression of rictor, a vital component of mTORC2, significantly abolished the adverse effects of BCKA on apoptosis susceptibility of cardiomyocytes. These results indicate that BCKA contribute to vulnerability of cardiomyocytes in stimulated stress via inactivation of mTORC2-Akt pathway.
authors.affiliation: Department of Cardiology, Xijing Hospital, Fourth Military Medical University, Xi'an, 710032, China.
authors.forename: Xiong
authors.initials: X
authors.lastname: Guo
authors.affiliation: Department of Cardiology, Xijing Hospital, Fourth Military Medical University, Xi'an, 710032, China.
authors.forename: Chong
authors.initials: C
authors.lastname: Huang
authors.affiliation: Department of Cardiology, Xijing Hospital, Fourth Military Medical University, Xi'an, 710032, China.
authors.forename: Kun
authors.initials: K
authors.lastname: Lian
authors.affiliation: Department of Cardiology, Xijing Hospital, Fourth Military Medical University, Xi'an, 710032, China.
authors.forename: Shan
authors.initials: S
authors.lastname: Wang
authors.affiliation: Department of Cardiology, Xijing Hospital, Fourth Military Medical University, Xi'an, 710032, China.
authors.forename: Huishou
authors.initials: H
authors.lastname: Zhao
authors.affiliation: Department of Cardiology, Xijing Hospital, Fourth Military Medical University, Xi'an, 710032, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Yan
authors.affiliation: Department of Cardiology, Xijing Hospital, Fourth Military Medical University, Xi'an, 710032, China.
authors.forename: Xiaomeng
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Cardiology, Xijing Hospital, Fourth Military Medical University, Xi'an, 710032, China.
authors.forename: Jinglong
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Cardiology, Xijing Hospital, Fourth Military Medical University, Xi'an, 710032, China.
authors.forename: Huaning
authors.initials: H
authors.lastname: Xie
authors.affiliation: Department of Radiology, Xijing Hospital, Fourth Military Medical University, Xi'an, 710032, China.
authors.forename: Rui
authors.initials: R
authors.lastname: An
authors.affiliation: Department of Cardiology, Xijing Hospital, Fourth Military Medical University, Xi'an, 710032, China. Electronic address: lingtao2006@gmail.com.
authors.forename: Ling
authors.initials: L
authors.lastname: Tao
mesh_terms: D000597:Amino Acids, Branched-Chain / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D016923:Cell Death / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D015536:Down-Regulation / Q000187:drug effects; D007545:Isoproterenol / Q000494:pharmacology; D000076225:Mechanistic Target of Rapamycin Complex 2; D008810:Mice, Inbred C57BL; D046912:Multiprotein Complexes / Q000378:metabolism*; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D000076226:Rapamycin-Insensitive Companion of mTOR Protein; D015398:Signal Transduction / Q000187:drug effects; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism*
chemical_list: D000597:Amino Acids, Branched-Chain; D002352:Carrier Proteins; D046912:Multiprotein Complexes; D000076226:Rapamycin-Insensitive Companion of mTOR Protein; C550254:rictor protein, rat; D000076225:Mechanistic Target of Rapamycin Complex 2; D051057:Proto-Oncogene Proteins c-akt; D058570:TOR Serine-Threonine Kinases; D007545:Isoproterenol
keywords: Akt; Apoptosis; BCKA; Diabetes; Isoproterenol; mTORC2