Inhibition of glutaminase 1-mediated glutaminolysis improves pathological cardiac remodeling
Sachiko Yoshikawa, Manabu Nagao, Ryuji Toh, Masakazu Shinohara, Takuya Iino, Yasuhiro Irino, Makoto Nishimori, Hidekazu Tanaka, Seimi Satomi‐Kobayashi, Tatsuro Ishida, Ken‐ichi Hirata
Abstract
To our knowledge, this study is the first to demonstrate that increased GLS1 expression and subsequent activation of glutaminolysis are associated with exacerbation of cardiac hypertrophy and fibrosis. Inhibiting GLS1 antagonized the adverse cardiac remodeling in vitro and in vivo, partly due to reduction of glutamine-derived metabolites, which are necessary for cellular growth and proliferation. Increased glutamine utilization for anabolic reactions in cardiac cells may be related to the pathogenesis and development of HF.
Topics & Concepts
GlutaminolysisGlutaminaseGlutamineInternal medicineCardiac fibrosisChemistryEndocrinologyPhospholambanBiologyCell biologyFibrosisBiochemistryPhosphorylationAmino acidMedicineCardiovascular Function and Risk FactorsCancer, Hypoxia, and MetabolismAdvanced MRI Techniques and Applications