Open AccessmTORC 1 is involved in the regulation of branched‐chain amino acid catabolism in mouse heart
Author(s) -
Zhen Hongmin,
Kitaura Yasuyuki,
Kadota Yoshihiro,
Ishikawa Takuya,
Kondo Yusuke,
Xu Minjun,
Morishita Yukako,
Ota Miki,
Ito Tomokazu,
Shimomura Yoshiharu
Publication year - 2016
Publication title -
febs open bio
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.718
H-Index - 31
ISSN - 2211-5463
DOI - 10.1002/2211-5463.12007
Subject(s) - catabolism , mtorc1 , leucine , branched chain amino acid , amino acid , ribosomal protein s6 , biochemistry , kinase , phosphorylation , chemistry , endocrinology , medicine , biology , metabolism , protein kinase a , protein phosphorylation , protein kinase b
The branched‐chain α‐ketoacid dehydrogenase ( BCKDH ) complex regulates branched‐chain amino acid ( BCAA ) catabolism by controlling the second step of this catabolic pathway. In the present study, we examined the in vivo effects of treatment with an mTORC 1 inhibitor, rapamycin, on cardiac BCKDH complex activity in mice. Oral administration of leucine in control mice significantly activated the cardiac BCKDH complex with an increase in cardiac concentrations of leucine and α‐ketoisocaproate. However, rapamycin treatment significantly suppressed the leucine‐induced activation of the complex despite similar increases in cardiac leucine and α‐ketoisocaproate levels. Rapamycin treatment fully inhibited mTORC 1 activity, measured by the phosphorylation state of ribosomal protein S6 kinase 1. These results suggest that mTORC 1 is involved in the regulation of cardiac BCAA catabolism.