The adipokine chemerin augments vascular reactivity to contractile stimuli via activation of the MEK-ERK1/2 pathway
Lobato, N. S. and Neves, K. B. and Filgueira, F. P. and Fortes, Z. B. and Carvalho, M. H. C. and Webb, R. C. and Oliveira, A. M. and Tostes, R. C. (2012) The adipokine chemerin augments vascular reactivity to contractile stimuli via activation of the MEK-ERK1/2 pathway. Life Sciences, 91 (13-14). pp. 600-606. ISSN 0024-3205 (https://doi.org/10.1016/j.lfs.2012.04.013)
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Abstract
Aims 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. Main 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 24 h), and isometric contraction was recorded. Protein expression was determined by Western blotting. Key findings Constrictor responses to phenylephrine (PE) and ET-1 were increased in vessels treated for 1 h with chemerin. Chemerin incubation for 24 h 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 24 h. 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. Significance 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.
ORCID iDs
Lobato, N. S., Neves, K. B. ORCID: https://orcid.org/0000-0001-5158-9263, Filgueira, F. P., Fortes, Z. B., Carvalho, M. H. C., Webb, R. C., Oliveira, A. M. and Tostes, R. C.;-
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Item type: Article ID code: 82754 Dates: DateEvent15 October 2012Published3 April 2012AcceptedNotes: The adipokine chemerin augments vascular reactivity to contractile stimuli via activation of the MEK-ERK1/2 pathway, Life Sciences, Volume 91, Issues 13–14, 2012, https://doi.org/10.1016/j.lfs.2012.04.013 Subjects: Medicine Department: Faculty of Science > Strathclyde Institute of Pharmacy and Biomedical Sciences
Faculty of Science > PhysicsDepositing user: Pure Administrator Date deposited: 13 Oct 2022 13:15 Last modified: 28 Nov 2024 01:25 URI: https://strathprints.strath.ac.uk/id/eprint/82754