title: The Adipokine Chemerin Induces Apoptosis in Cardiomyocytes.
abstract: BACKGROUND
  The adipokine chemerin has been associated with cardiovascular disease. We investigated the effects of chemerin on viability and intracellular signalling in murine cardiomyocytes, and the effects of insulin and TNF-α on cardiomyocyte chemerin production.
  
  
  METHODS
  Hoechst dye vital staining and cell cycle analysis were used to analyse the viability of murine cardiac cells in culture. Western blot was used to explore the phosphorylation of AKT and caspase-9 activity in neonatal rat cardiomyocytes and HL-1 cells. Finally, RT-qPCR, ELISA and western blot were performed to examine chemerin and CMKLR1 expression after insulin and TNF-α treatment in cardiac cells.
  
  
  RESULTS
  Chemerin treatment increased apoptosis, reduced phosphorylation of AKT at Thr308 and increased caspase-9 activity in murine cardiomyocytes. Insulin treatment lowered chemerin and CMKLR1 mRNA and protein levels, and the amount of chemerin in the cell media, while TNF-α treatment increased chemerin mRNA and protein levels but decreased expression of the CMKLR1 gene.
  
  
  CONCLUSIONS
  Chemerin induces apoptosis, reduces AKT phosphorylation and increases the cleavage of caspase-9 in murine cardiomyocytes. The expression of chemerin is regulated by important metabolic (insulin) and inflammatory (TNF-α) mediators at cardiac level. Our results suggest that chemerin could play a role in the physiopathology of cardiac diseases.
authors: Cellular and Molecular Cardiology Research Unit and Department of Cardiology, Institute of Biomedical Research and University Clinical Hospital, Santiago de Compostela, Spain.
authors: Diego
authors: D
authors: Rodríguez-Penas
authors: Sandra
authors: S
authors: Feijóo-Bandín
authors: Vanessa
authors: V
authors: García-Rúa
authors: Ana
authors: A
authors: Mosquera-Leal
authors: Darío
authors: D
authors: Durán
authors: Alfonso
authors: A
authors: Varela
authors: Manuel
authors: M
authors: Portolés
authors: Esther
authors: E
authors: Roselló-Lletí
authors: Miguel
authors: M
authors: Rivera
authors: Carlos
authors: C
authors: Diéguez
authors: Oreste
authors: O
authors: Gualillo
authors: José Ramón
authors: JR
authors: González-Juanatey
authors: Francisca
authors: F
authors: Lago
mesh_terms: D054392:Adipokines / Q000378:metabolism*; D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D053453:Caspase 9 / Q000378:metabolism; D002478:Cells, Cultured; D018925:Chemokines / Q000378:metabolism*; D007328:Insulin / Q000378:metabolism; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism*; D051379:Mice; D032383:Myocytes, Cardiac / Q000378:metabolism*; D010766:Phosphorylation / Q000502:physiology; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D019707:Receptors, Chemokine / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D054392:Adipokines; C102741:CMKLR1 protein, human; D018925:Chemokines; D007328:Insulin; D036341:Intercellular Signaling Peptides and Proteins; D012333:RNA, Messenger; C560738:Rarres2 protein, rat; D019707:Receptors, Chemokine; D014409:Tumor Necrosis Factor-alpha; D051057:Proto-Oncogene Proteins c-akt; D053453:Caspase 9