title: The adipokine chemerin augments vascular reactivity to contractile stimuli via activation of the MEK-ERK1/2 pathway.
abstract: OBJECTIVE
  Cytokines interfere with signaling pathways and mediators of vascular contraction. Endothelin-1 (ET-1) plays a major role on vascular dysfunction in conditions characterized by increased circulating levels of adipokines. In the present study we tested the hypothesis that the adipokine chemerin increases vascular contractile responses via activation of ET-1/ET-1 receptors-mediated pathways.
  
  
  METHODS
  Male, 10-12 week-old Wistar rats were used. Endothelium-intact and endothelium-denuded aortic rings were incubated with chemerin (0.5 ng/mL or 5 ng/mL, for 1 or 24h), and isometric contraction was recorded. Protein expression was determined by Western blotting.
  
  
  RESULTS
  Constrictor responses to phenylephrine (PE) and ET-1 were increased in vessels treated for 1h with chemerin. Chemerin incubation for 24h decreased PE contractile response whereas it increased the sensitivity to ET-1. Endothelium removal significantly potentiated chemerin effects on vascular contractile responses to PE and ET-1. Incubation with either an ERK1/2 inhibitor (PD98059) or ETA antagonist (BQ123) abolished chemerin effects on PE- and ET-1-induced vasoconstriction. Phosphorylation of MEK1/2 and ERK1/2 was significantly increased in vessels treated with chemerin for 1 and 24h. Phosphorylation of these proteins was further increased in vessels incubated with ET-1 plus chemerin. ET-1 increased MEK1/2, ERK1/2 and MKP1 protein expression to values observed in vessels treated with chemerin.
  
  
  CONCLUSIONS
  Chemerin increases contractile responses to PE and ET-1 via ERK1/2 activation. Our study contributes to a better understanding of the mechanisms by which the adipose tissue affects vascular function and, consequently, the vascular alterations present in obesity and related diseases.
authors.affiliation: Department of Biological Sciences, Federal University of Goias, Jatai, GO, Brazil. nubialobato@yahoo.com.br
authors.forename: N S
authors.initials: NS
authors.lastname: Lobato
authors.forename: K B
authors.initials: KB
authors.lastname: Neves
authors.forename: F P
authors.initials: FP
authors.lastname: Filgueira
authors.forename: Z B
authors.initials: ZB
authors.lastname: Fortes
authors.forename: M H C
authors.initials: MH
authors.lastname: Carvalho
authors.forename: R C
authors.initials: RC
authors.lastname: Webb
authors.forename: A M
authors.initials: AM
authors.lastname: Oliveira
authors.forename: R C
authors.initials: RC
authors.lastname: Tostes
mesh_terms: D054392:Adipokines / Q000008:administration & dosage* / Q000378:metabolism; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects* / Q000378:metabolism; D015153:Blotting, Western; D018925:Chemokines; D004305:Dose-Response Relationship, Drug; D019332:Endothelin-1 / Q000008:administration & dosage / Q000378:metabolism; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism; D005419:Flavonoids / Q000494:pharmacology; D036341:Intercellular Signaling Peptides and Proteins; D048369:MAP Kinase Kinase 1 / Q000378:metabolism; D048370:MAP Kinase Kinase 2 / Q000378:metabolism; D008297:Male; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism*; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism*; D010456:Peptides, Cyclic / Q000494:pharmacology; D010656:Phenylephrine / Q000494:pharmacology; D010766:Phosphorylation / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors
chemical_list: D054392:Adipokines; D018925:Chemokines; D019332:Endothelin-1; D005419:Flavonoids; D036341:Intercellular Signaling Peptides and Proteins; D010456:Peptides, Cyclic; C560738:Rarres2 protein, rat; D010656:Phenylephrine; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D048369:MAP Kinase Kinase 1; D048370:MAP Kinase Kinase 2; C072247:cyclo(Trp-Asp-Pro-Val-Leu); C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one