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BioMed Research International
Volume 2013 (2013), Article ID 276808, 9 pages
http://dx.doi.org/10.1155/2013/276808
Research Article

Frataxin mRNA Isoforms in FRDA Patients and Normal Subjects: Effect of Tocotrienol Supplementation

1Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna, 40126 Bologna, Italy
2Department of Pharmaceutical Sciences, University of Ferrara, 44100 Ferrara, Italy
3ANFFAS ONLUS Macerata, 62100 Macerata, Italy
4Child Neurology and Psychiatry Unit, IRCCS Institute of Neurological Sciences of Bologna, Bologna, 40100 Bologna, Italy
5Biocomputing Group, CIRI-Health Science and Technology, Department of Biology, Bologna 40126, Italy

Received 15 April 2013; Revised 6 August 2013; Accepted 17 August 2013

Academic Editor: Chen-Hsiung Hung

Copyright © 2013 Provvidenza Maria Abruzzo et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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.