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Role of transient receptor potential vanilloid 1 in regulating erythropoietin-induced activation of endothelial nitric oxide synthase.
- Source :
-
Acta Physiologica . Feb2017, Vol. 219 Issue 2, p465-477. 13p. - Publication Year :
- 2017
-
Abstract
- Aims Erythropoietin ( EPO), the key hormone involved in erythropoiesis, beneficially affects endothelial cells ( ECs), but the detailed mechanisms are yet to be completely understood. In this study, we investigated the role of transient receptor potential vanilloid type 1 ( TRPV1), a ligand-gated non-selective calcium (Ca2+) channel, in EPO-mediated endothelial nitric oxide synthase ( eNOS) activation and angiogenesis. Methods and results In ECs, EPO time dependently increased intracellular levels of calcium; this increase was abrogated by the Ca2+ chelators and pharmacological inhibitors of TRPV1 in bovine aortic ECs (BAECs) and TRPV1-transfected HEK293 cells. In addition, EPO-induced nitrite oxide ( NO) production, phosphorylation of eNOS, Akt and AMP-activated protein kinase ( AMPK) and the formation of TRPV1-Akt- AMPK- eNOS complex as well as tube formation were diminished by the pharmacological inhibition of TRPV1 in BAECs. Moreover, EPO time dependently induced the phosphorylation of phospholipase C- γ1 ( PLC- γ1). Inhibition of PLC- γ1 activity blunted the EPO-induced Ca2+ influx, eNOS phosphorylation, TRPV1- eNOS complex formation and NO production. The phosphorylated level of eNOS increased in the aortas of EPO-treated wild-type ( WT) mice or EPO-transgenic (Tg) mice but not in those of EPO-treated TRPV1-deficient ( TRPV1−/−) mice or EPO-Tg/ TRPV1−/− mice. Matrigel plug assay showed that EPO-induced angiogenesis was abrogated in TRPV1 antagonist capsazepine-treated WT mice and TRPV1−/− mice. Conclusion These findings indicate the EPO-induced Ca2+ influx via the activation of the PLC- γ1 signalling pathway, which leads to TRPV1 activation and consequently increases the association of the TRPV1-Akt- AMPK- eNOS complex, eNOS activation, NO production and angiogenesis. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 17481708
- Volume :
- 219
- Issue :
- 2
- Database :
- Academic Search Index
- Journal :
- Acta Physiologica
- Publication Type :
- Academic Journal
- Accession number :
- 121000073
- Full Text :
- https://doi.org/10.1111/apha.12723