caa a22 4500 445824654 CHVBK 20180317145255.0 cr unu---uuuuu 170323e20110301xx s 000 0 eng 10.1007/s00246-010-9856-9 doi (NATIONALLICENCE)springer-10.1007/s00246-010-9856-9 Catabolism of Branched-Chain Amino Acids in Heart Failure: Insights from Genetic Models [Elektronische Daten] [Haipeng Sun, Gang Lu, Shuxun Ren, Jaunian Chen, Yibin Wang] Genetic defects in amino acid metabolism are major causes of newborn diseases that often lead to abnormal development and function of the central nervous system. Their direct impact on cardiac development and function has rarely been investigated. Recently, the authors have established that a mitochondrial targeted 2C-type ser/thr protein phosphatase, PP2Cm, is the endogenous phosphatase of the branched-chain alpha keto acid-dehydrogenase complex (BCKD) and functions as a key regulator in branched-chain amino acid catabolism and homeostasis. Genetic inactivation of PP2Cm in mice leads to significant elevation in plasma concentrations of branched-chain amino acids and branched-chain keto acids at levels similar to those associated with intermediate mild forms of maple syrup urine disease. In addition to neuronal tissues, PP2Cm is highly expressed in cardiac muscle, and its expression is diminished in a heart under pathologic stresses. Whereas phenotypic features of heart failure are seen in PP2Cm-deficient zebra fish embryos, cardiac function in PP2Cm-null mice is compromised at a young age and deteriorates faster by mechanical overload. These observations suggest that the catabolism of branched-chain amino acids also has physiologic significance in maintaining normal cardiac function. Defects in PP2Cm-mediated catabolism of branched-chain amino acids can be a potential novel mechanism not only for maple syrup urine disease but also for congenital heart diseases and heart failure. The Author(s), 2010 Amino acid metabolism nationallicence Branched-chain amino acid catabolism nationallicence Branched-chain alpha keto acid-dehydrogenase complex nationallicence PP2Cm nationallicence Sun Haipeng Division of Molecular Medicine, Departments of Anesthesiology, Medicine and Physiology, Molecular Biology Institute, Cardiovascular Research Laboratories, David Geffen School of Medicine, CSH, Room BH 569, 650 Charles E. Young Drive, 90095, Los Angeles, CA, USA aut Lu Gang Division of Molecular Medicine, Departments of Anesthesiology, Medicine and Physiology, Molecular Biology Institute, Cardiovascular Research Laboratories, David Geffen School of Medicine, CSH, Room BH 569, 650 Charles E. Young Drive, 90095, Los Angeles, CA, USA aut Ren Shuxun Division of Molecular Medicine, Departments of Anesthesiology, Medicine and Physiology, Molecular Biology Institute, Cardiovascular Research Laboratories, David Geffen School of Medicine, CSH, Room BH 569, 650 Charles E. Young Drive, 90095, Los Angeles, CA, USA aut Chen Jaunian Division of Molecular Medicine, Departments of Anesthesiology, Medicine and Physiology, Molecular Biology Institute, Cardiovascular Research Laboratories, David Geffen School of Medicine, CSH, Room BH 569, 650 Charles E. Young Drive, 90095, Los Angeles, CA, USA aut Wang Yibin Division of Molecular Medicine, Departments of Anesthesiology, Medicine and Physiology, Molecular Biology Institute, Cardiovascular Research Laboratories, David Geffen School of Medicine, CSH, Room BH 569, 650 Charles E. Young Drive, 90095, Los Angeles, CA, USA aut Pediatric Cardiology Springer-Verlag 32/3(2011-03-01), 305-310 0172-0643 32:3<305 2011 32 246 https://doi.org/10.1007/s00246-010-9856-9 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s00246-010-9856-9 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Sun Haipeng Division of Molecular Medicine, Departments of Anesthesiology, Medicine and Physiology, Molecular Biology Institute, Cardiovascular Research Laboratories, David Geffen School of Medicine, CSH, Room BH 569, 650 Charles E. Young Drive, 90095, Los Angeles, CA, USA aut NATIONALLICENCE 700 1- Lu Gang Division of Molecular Medicine, Departments of Anesthesiology, Medicine and Physiology, Molecular Biology Institute, Cardiovascular Research Laboratories, David Geffen School of Medicine, CSH, Room BH 569, 650 Charles E. Young Drive, 90095, Los Angeles, CA, USA aut NATIONALLICENCE 700 1- Ren Shuxun Division of Molecular Medicine, Departments of Anesthesiology, Medicine and Physiology, Molecular Biology Institute, Cardiovascular Research Laboratories, David Geffen School of Medicine, CSH, Room BH 569, 650 Charles E. Young Drive, 90095, Los Angeles, CA, USA aut NATIONALLICENCE 700 1- Chen Jaunian Division of Molecular Medicine, Departments of Anesthesiology, Medicine and Physiology, Molecular Biology Institute, Cardiovascular Research Laboratories, David Geffen School of Medicine, CSH, Room BH 569, 650 Charles E. Young Drive, 90095, Los Angeles, CA, USA aut NATIONALLICENCE 700 1- Wang Yibin Division of Molecular Medicine, Departments of Anesthesiology, Medicine and Physiology, Molecular Biology Institute, Cardiovascular Research Laboratories, David Geffen School of Medicine, CSH, Room BH 569, 650 Charles E. Young Drive, 90095, Los Angeles, CA, USA aut NATIONALLICENCE 773 0- Pediatric Cardiology Springer-Verlag 32/3(2011-03-01), 305-310 0172-0643 32:3<305 2011 32 246 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer