title: Linking αMSH with PPARγ in B16-F10 melanoma.
abstract: We have discovered a new α-melanocyte stimulating hormone (α-MSH)/peroxisome proliferator activated receptor-γ (PPAR-γ) connection in B16-F10 cells. Both PPAR-γ up-regulation and its induction as an active transcription factor were observed in response to α-MSH. The α-MSH/PPAR-γ connection influenced both pigmentation and proliferation. The forskolin-stimulated cAMP/PKA pathway was not able to induce either PPAR-γ translocation into the nucleus or PPAR-γ transcriptional activity. As the melanocortin-1 receptor, the specific receptor for the α-MSH, is a G-protein coupled receptor, we wondered whether the phosphatidylinositol [PI(4,5)P(2) /PLC(β) ] signal pathway was involved in mediating the α-MSH-dependent PPAR-γ activation. Employing inhibitors of PI(4,5)P(2) /PLC(β)  pathway, the results of our experiments suggested that this pathway was promoted by α-MSH and that α-MSH played a role in mediating PPAR-γ activation. We have demonstrated, for the first time, that α-MSH induces the PI(4,5)P(2) /PLC(β)  pathway, through analysis of the basic steps of the pathway. The α-MSH effect on PPAR-γ was independent of animal species and was not correlated with the physio-pathological status.
authors.affiliation: Laboratory of Cutaneous Physiopathology and Integrated Centre of Metabolomics Research, San Gallicano Dermatological Institute (IRCCS), Rome, Italy.
authors.forename: Vittoria
authors.initials: V
authors.lastname: Maresca
authors.forename: Enrica
authors.initials: E
authors.lastname: Flori
authors.forename: Emanuela
authors.initials: E
authors.lastname: Camera
authors.forename: Barbara
authors.initials: B
authors.lastname: Bellei
authors.forename: Nicaela
authors.initials: N
authors.lastname: Aspite
authors.forename: Matteo
authors.initials: M
authors.lastname: Ludovici
authors.forename: Caterina
authors.initials: C
authors.lastname: Catricalà
authors.forename: Giorgia
authors.initials: G
authors.lastname: Cardinali
authors.forename: Mauro
authors.initials: M
authors.lastname: Picardo
mesh_terms: D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D000242:Cyclic AMP / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D004075:Diglycerides / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006367:HeLa Cells; D006801:Humans; D006868:Hydrolysis / Q000187:drug effects; D007295:Inositol Phosphates / Q000378:metabolism; D008546:Melanoma, Experimental / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D047495:PPAR gamma / Q000235:genetics / Q000378:metabolism*; D054799:Phospholipase C beta / Q000378:metabolism; D021381:Protein Transport / Q000187:drug effects; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics; D012878:Skin Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D000521:alpha-MSH / Q000494:pharmacology*
chemical_list: D004075:Diglycerides; D007295:Inositol Phosphates; D047495:PPAR gamma; D012333:RNA, Messenger; D016718:Arachidonic Acid; D000521:alpha-MSH; C066454:inositol 4,5-bisphosphate; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases; D054799:Phospholipase C beta; D002118:Calcium