The PI3K pathway induced by αMSH exerts a negative feedback on melanogenesis and contributes to the release of pigment
| Autor: | Giorgia Cardinali, Vittoria Maresca, Stefania Briganti, Sarah Mosca, Enrica Flori, Anna Maria Mileo, Irene Bottillo |
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| Rok vydání: | 2019 |
| Předmět: |
melanogenesis
0301 basic medicine pAKT Melanoma Experimental Dermatology PI3K General Biochemistry Genetics and Molecular Biology B16-F10 03 medical and health sciences Mice Phosphatidylinositol 3-Kinases 0302 clinical medicine Downregulation and upregulation Animals Humans αMSH Phosphorylation Receptor Protein kinase B PI3K/AKT/mTOR pathway G protein-coupled receptor Feedback Physiological Melanins Chemistry Pigmentation AKT apoptosis melanin Cell biology 030104 developmental biology Oncology Apoptosis Cell culture alpha-MSH 030220 oncology & carcinogenesis Melanocytes melanocytes Proto-Oncogene Proteins c-akt |
| Zdroj: | Pigment cellmelanoma researchREFERENCES. 34(1) |
| ISSN: | 1755-148X |
| Popis: | The melanocortin-1 receptor (MC1R) belongs to the family of the G protein-coupled receptor (GPCR). Activated GPCRs can promote the phosphoinositide 3-kinase (PI3K) pathway. Few studies deal with the role of the PI3K pathway activation in response to αMSH. On B16-F10 cell line, we investigated the αMSH-dependent modulation of pAKT/AKT, as a key element of the PI3K pathway after rapid and prolonged stimulation. We demonstrated that αMSH triggers a rapid modulation of AKT which culminates in an increase in its phosphorylation. We highlighted a comparable upregulation of pAKT after exposure to αMSH on primary cultures of normal human melanocytes (NHMs) expressing a wild-type MC1R. On B16-F10 cells, NHMs, and an ex vivo model of human skin biopsies, we explored the influence of PI3K/AKT signaling triggered by αMSH, focusing on the control of melanogenesis and pigment release. We showed that the αMSH-dependent PI3K/AKT pathway exerts a negative feedback on melanogenesis and promotes the extracellular release of pigment. We strengthened the role of the PI3K/AKT pathway triggered by αMSH in preserving redox equilibrium and genome integrity, highlighting its role in affecting cell survival. |
| Databáze: | OpenAIRE |
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