Frataxin mRNA Isoforms in FRDA Patients and Normal Subjects: Effect of Tocotrienol Supplementation. (23rd September 2013)

• Record Type: Journal Article
• Authors: Abruzzo, Provvidenza Maria; Marini, Marina; Bolotta, Alessandra; Malisardi, Gemma; Manfredini, Stefano; Ghezzo, Alessandro; Pini, Antonella; Tasco, Gianluca; Casadio, Rita
• Other Names: Hung Chen-Hsiung Academic Editor.
• Is Part Of: BioMed research international. Volume 2013(2013)
• Publication Date: 2013-09-23
• Subjects: Medicine -- Periodicals; Biology -- Periodicals; Biotechnology -- Periodicals; Life sciences -- Periodicals; 610.5
• DOI: 10.1155/2013/276808
• Languages: English
• ISSNs: 2314-6133

Abstract

Abstract : Friedreich's ataxia (FRDA) is caused by deficient expression of the mitochondrial protein frataxin involved in the formation of iron-sulphur complexes and by consequent oxidative stress. We analysed low-dose tocotrienol supplementation effects on the expression of the three splice variant isoforms ( FXN-1, FXN-2, and FXN-3 ) in mononuclear blood cells of FRDA patients and healthy subjects. In FRDA patients, tocotrienol leads to a specific and significant increase of FXN-3 expression while not affecting FXN-1 and FXN-2 expression. Since no structural and functional details were available for FNX-2 and FXN-3, 3D models were built. FXN-1, the canonical isoform, was then docked on the human iron-sulphur complex, and functional interactions were computed; when FXN-1 was replaced by FXN-2 or FNX-3, we found that the interactions were maintained, thus suggesting a possible biological role for both isoforms in human cells. Finally, in order to evaluate whether tocotrienol enhancement of FXN-3 was mediated by an increase in peroxisome proliferator-activated receptor- γ (PPARG), PPARG expression was evaluated. At a low dose of tocotrienol, the increase of FXN-3 expression appeared to be independent of PPARG expression. Our data show that it is possible to modulate the mRNA expression of the minor frataxin isoforms and that they may have a functional role.