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Metabolic reprogramming of murine cardiomyocytes during autophagy requires the extracellular nutrient sensor decorin.
Gubbiotti, Maria A; Seifert, Erin; Rodeck, Ulrich; Hoek, Jan B; Iozzo, Renato V.
Afiliação
  • Gubbiotti MA; From the Department of Pathology, Anatomy and Cell Biology and the Cancer Cell Biology and Signaling Program, Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania 19107.
  • Seifert E; From the Department of Pathology, Anatomy and Cell Biology and the Cancer Cell Biology and Signaling Program, Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania 19107.
  • Rodeck U; MitoCare Center, Department of Pathology, Anatomy and Cell Biology, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, and.
  • Hoek JB; From the Department of Pathology, Anatomy and Cell Biology and the Cancer Cell Biology and Signaling Program, Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania 19107.
  • Iozzo RV; Department of Dermatology and Cutaneous Biology, Thomas Jefferson University, Philadelphia, Pennsylvania 19107.
J Biol Chem ; 293(43): 16940-16950, 2018 10 26.
Article em En | MEDLINE | ID: mdl-30049794
The extracellular matrix is a master regulator of tissue homeostasis in health and disease. Here we examined how the small, leucine-rich, extracellular matrix proteoglycan decorin regulates cardiomyocyte metabolism during fasting in vivo First, we validated in Dcn-/- mice that decorin plays an essential role in autophagy induced by fasting. High-throughput metabolomics analyses of cardiac tissue in Dcn-/- mice subjected to fasting revealed striking differences in the hexosamine biosynthetic pathway resulting in aberrant cardiac O-ß-N-acetylglycosylation as compared with WT mice. Functionally, Dcn-/- mice maintained cardiac function at a level comparable with nonfasted animals whereas fasted WT mice showed reduced ejection fraction. Collectively, our results suggest that reduced sensing of nutrient deprivation in the absence of decorin preempts functional adjustments of cardiac output associated with metabolic reprogramming.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Autofagia / Nutrientes / Miócitos Cardíacos / Matriz Extracelular / Metaboloma / Decorina Idioma: En Ano de publicação: 2018 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Autofagia / Nutrientes / Miócitos Cardíacos / Matriz Extracelular / Metaboloma / Decorina Idioma: En Ano de publicação: 2018 Tipo de documento: Article