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Copper regulates cyclic-AMP-dependent lipolysis.
Krishnamoorthy, Lakshmi; Cotruvo, Joseph A; Chan, Jefferson; Kaluarachchi, Harini; Muchenditsi, Abigael; Pendyala, Venkata S; Jia, Shang; Aron, Allegra T; Ackerman, Cheri M; Wal, Mark N Vander; Guan, Timothy; Smaga, Lukas P; Farhi, Samouil L; New, Elizabeth J; Lutsenko, Svetlana; Chang, Christopher J.
Afiliação
  • Krishnamoorthy L; Department of Chemistry, University of California, Berkeley, California, USA.
  • Cotruvo JA; Howard Hughes Medical Institute, University of California, Berkeley, California, USA.
  • Chan J; Department of Chemistry, University of California, Berkeley, California, USA.
  • Kaluarachchi H; Department of Chemistry, University of California, Berkeley, California, USA.
  • Muchenditsi A; Department of Chemistry, University of California, Berkeley, California, USA.
  • Pendyala VS; Department of Physiology, Johns Hopkins University, School of Medicine, Baltimore, Maryland, USA.
  • Jia S; Department of Physiology, Johns Hopkins University, School of Medicine, Baltimore, Maryland, USA.
  • Aron AT; Department of Chemistry, University of California, Berkeley, California, USA.
  • Ackerman CM; Department of Chemistry, University of California, Berkeley, California, USA.
  • Wal MN; Department of Chemistry, University of California, Berkeley, California, USA.
  • Guan T; Department of Chemistry, University of California, Berkeley, California, USA.
  • Smaga LP; Department of Chemistry, University of California, Berkeley, California, USA.
  • Farhi SL; Department of Chemistry, University of California, Berkeley, California, USA.
  • New EJ; Department of Chemistry, University of California, Berkeley, California, USA.
  • Lutsenko S; Department of Chemistry, University of California, Berkeley, California, USA.
  • Chang CJ; Department of Physiology, Johns Hopkins University, School of Medicine, Baltimore, Maryland, USA.
Nat Chem Biol ; 12(8): 586-92, 2016 08.
Article em En | MEDLINE | ID: mdl-27272565
ABSTRACT
Cell signaling relies extensively on dynamic pools of redox-inactive metal ions such as sodium, potassium, calcium and zinc, but their redox-active transition metal counterparts such as copper and iron have been studied primarily as static enzyme cofactors. Here we report that copper is an endogenous regulator of lipolysis, the breakdown of fat, which is an essential process in maintaining body weight and energy stores. Using a mouse model of genetic copper misregulation, in combination with pharmacological alterations in copper status and imaging studies in a 3T3-L1 white adipocyte model, we found that copper regulates lipolysis at the level of the second messenger, cyclic AMP (cAMP), by altering the activity of the cAMP-degrading phosphodiesterase PDE3B. Biochemical studies of the copper-PDE3B interaction establish copper-dependent inhibition of enzyme activity and identify a key conserved cysteine residue in a PDE3-specific loop that is essential for the observed copper-dependent lipolytic phenotype.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: AMP Cíclico / Cobre / Inibidores da Fosfodiesterase 3 / Lipólise Limite: Animals Idioma: En Ano de publicação: 2016 Tipo de documento: Article
Texto completo
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: AMP Cíclico / Cobre / Inibidores da Fosfodiesterase 3 / Lipólise Limite: Animals Idioma: En Ano de publicação: 2016 Tipo de documento: Article