PUBLICATION
α-Melanocyte-Stimulating Hormone Attenuates Neovascularization by Inducing Nitric Oxide Deficiency via MC-Rs/PKA/NF-κB Signaling
- Authors
- Weng, W.T., Wu, C.S., Wang, F.S., Wu, C.Y., Ma, Y.L., Chan, H.H., Wu, D.C., Wu, J.C., Chu, T.H., Huang, S.C., Tai, M.H.
- ID
- ZDB-PUB-181206-4
- Date
- 2018
- Source
- International Journal of Molecular Sciences 19(12): (Journal)
- Registered Authors
- Keywords
- HUVECs, melanocortin receptors (MC-Rs), nitric oxide (NO), α-melanocyte-stimulating hormone (α-MSH)
- MeSH Terms
-
- Cyclic AMP-Dependent Protein Kinases/metabolism*
- Human Umbilical Vein Endothelial Cells
- Humans
- NF-kappa B/metabolism*
- Neovascularization, Pathologic/drug therapy*
- Neovascularization, Pathologic/metabolism*
- Nitric Oxide
- RNA Interference
- Receptors, Melanocortin/metabolism*
- Signal Transduction/drug effects
- alpha-MSH/therapeutic use*
- PubMed
- 30513637 Full text @ Int. J. Mol. Sci.
Citation
Weng, W.T., Wu, C.S., Wang, F.S., Wu, C.Y., Ma, Y.L., Chan, H.H., Wu, D.C., Wu, J.C., Chu, T.H., Huang, S.C., Tai, M.H. (2018) α-Melanocyte-Stimulating Hormone Attenuates Neovascularization by Inducing Nitric Oxide Deficiency via MC-Rs/PKA/NF-κB Signaling. International Journal of Molecular Sciences. 19(12).
Abstract
α-melanocyte-stimulating hormone (α-MSH) has been characterized as a novel angiogenesis inhibitor. The homeostasis of nitric oxide (NO) plays an important role in neovascularization. However, it remains unclear whether α-MSH mitigates angiogenesis through modulation of NO and its signaling pathway. The present study elucidated the function and mechanism of NO signaling in α-MSH-induced angiogenesis inhibition using cultured human umbilical vein endothelial cells (HUVECs), rat aorta rings, and transgenic zebrafish. By Griess reagent assay, it was found α-MSH dose-dependently reduced the NO release in HUVECs. Immunoblotting and immunofluorescence analysis revealed α-MSH potently suppressed endothelial and inducible nitric oxide synthase (eNOS/iNOS) expression, which was accompanied with inhibition of nuclear factor kappa B (NF-κB) activities. Excessive supply of NO donor l-arginine reversed the α-MSH-induced angiogenesis inhibition in vitro and in vivo. By using antibody neutralization and RNA interference, it was delineated that melanocortin-1 receptor (MC1-R) and melanocortin-2 receptor (MC2-R) participated in α-MSH-induced inhibition of NO production and NF-κB/eNOS/iNOS signaling. This was supported by pharmaceutical inhibition of protein kinase A (PKA), the downstream effector of MC-Rs signaling, using H89 abolished the α-MSH-mediated suppression of NO release and eNOS/iNOS protein level. Therefore, α-MSH exerts anti-angiogenic function by perturbing NO bioavailability and eNOS/iNOS expression in endothelial cells.
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Human Disease / Model
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