title: Ascorbic acid inhibits PMP22 expression by reducing cAMP levels.
abstract: Charcot-Marie-Tooth [CMT] syndrome is the most common hereditary peripheral neuropathy. CMT1A, which accounts for 50% of all CMT cases, usually results from triploidy of the PMP22 gene. Preclinical trials using an animal model show that disabled mice force-fed with high doses of ascorbic acid partially recover muscular strength after a few months of treatment, and suggest that high doses of ascorbic acid repress PMP22 expression. In this study, we demonstrated that ascorbic acid represses PMP22 gene expression by acting on intracellular cAMP levels and adenylate cyclase activity. This action is dose dependent and specific to ascorbic acid, since repression is not observed after treatment with other antioxidants. The new properties of ascorbic acid are discussed, along with the implications of these findings for CMT disease treatment.
authors.affiliation: INSERM UMR491, Centre de Thérapie Génique, Génomique et de Biothérapies (CTGGB), IPHM-IFR125, Faculté de Médecine de la Timone, 27 bd Jean Moulin, 13385 Marseille cedex 5, France.
authors.forename: Ferdinand
authors.initials: F
authors.lastname: Kaya
authors.forename: Sophie
authors.initials: S
authors.lastname: Belin
authors.forename: Patrice
authors.initials: P
authors.lastname: Bourgeois
authors.forename: Joelle
authors.initials: J
authors.lastname: Micaleff
authors.forename: Olivier
authors.initials: O
authors.lastname: Blin
authors.forename: Michel
authors.initials: M
authors.lastname: Fontés
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D001205:Ascorbic Acid / Q000494:pharmacology*; D002461:Cell Line, Transformed; D000242:Cyclic AMP / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D005786:Gene Expression Regulation / Q000187:drug effects*; D051379:Mice; D009185:Myelin Proteins / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D012583:Schwann Cells / Q000187:drug effects; D012584:Sciatic Nerve / Q000166:cytology
chemical_list: D000975:Antioxidants; D009185:Myelin Proteins; C489545:Pmp22 protein, mouse; D000242:Cyclic AMP; D001205:Ascorbic Acid