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.
Highlights
Introduction α-Melanocyte-stimulating hormone (α-MSH) is a 13-amino acid neuropeptide derived from the precursor proopiomelanocortin (POMC), a pivotal stress hormone of hypothalamus/pituitary/adrenal gland (HPA) axis [1]. α-Melanocyte-Stimulating Hormone (α-MSH) is widely expressed in various tissues including hypothalamus, skin, and immune cells [2,3]
2A.1n. gNioigtreinceOsixsiIdneh(iNbiOtio)nDeficiency Participated in α-Melanocyte-Stimulating Hormone (α-MSH)-Induced Angiogenesis Inhibition
Because endothelial and inducible nitric oxide synthase contribute to NO metabolism in endothelial cells [25], we examined the effect of α-MSH on eNOS phosphorylation and eNOS/iNOS expression in human umbilical vein endothelial cells (HUVECs)
Summary
Introduction αMelanocyte-stimulating hormone (α-MSH) is a 13-amino acid neuropeptide derived from the precursor proopiomelanocortin (POMC), a pivotal stress hormone of hypothalamus/pituitary/adrenal gland (HPA) axis [1]. α-MSH is widely expressed in various tissues including hypothalamus, skin, and immune cells [2,3]. Melanocyte-stimulating hormone (α-MSH) is a 13-amino acid neuropeptide derived from the precursor proopiomelanocortin (POMC), a pivotal stress hormone of hypothalamus/pituitary/adrenal gland (HPA) axis [1]. Α-MSH is widely expressed in various tissues including hypothalamus, skin, and immune cells [2,3]. Cumulative evidence reveals that pharmacological α-MSH administration alleviates inflammatory reaction of acute respiratory distress syndrome, sepsis, rheumatoid arthritis, and inflammatory bowel disease [4,5,6]. Recent studies have demonstrated the anti-neoplastic potential of POMC, the precursor of α-MSH, in various types of cancer through neovascularization blockade [15,16,17]. The anti-angiogenic function of α-MSH is highly relevant to clinical science and could be applicable to diseases due to excessive neovascularization
Sign-in/Register to view highlights & summary 
Published Version (
Free)
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
