Frataxin mRNA isoforms in FRDA patients and normal subjects

Effect of tocotrienol supplementation

Provvidenza Maria Abruzzo, Marina Marini, Alessandra Bolotta, Gemma Malisardi, Stefano Manfredini, Alessandro Ghezzo, Antonella Pini, Gianluca Tasco, Rita Casadio

Research output: Contribution to journalArticle

6 Citations (Scopus)

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.

Original languageEnglish
Article number276808
JournalBioMed Research International
Volume2013
DOIs
Publication statusPublished - 2013

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Tocotrienols
Friedreich Ataxia
RNA Isoforms
Protein Isoforms
Sulfur
Iron
Cells
Peroxisome Proliferator-Activated Receptors
Oxidative stress
Mitochondrial Proteins
Blood Cells
Healthy Volunteers
Oxidative Stress
Blood
Messenger RNA
frataxin

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)

Cite this

Frataxin mRNA isoforms in FRDA patients and normal subjects : Effect of tocotrienol supplementation. / Abruzzo, Provvidenza Maria; Marini, Marina; Bolotta, Alessandra; Malisardi, Gemma; Manfredini, Stefano; Ghezzo, Alessandro; Pini, Antonella; Tasco, Gianluca; Casadio, Rita.

In: BioMed Research International, Vol. 2013, 276808, 2013.

Research output: Contribution to journalArticle

Abruzzo, Provvidenza Maria ; Marini, Marina ; Bolotta, Alessandra ; Malisardi, Gemma ; Manfredini, Stefano ; Ghezzo, Alessandro ; Pini, Antonella ; Tasco, Gianluca ; Casadio, Rita. / Frataxin mRNA isoforms in FRDA patients and normal subjects : Effect of tocotrienol supplementation. In: BioMed Research International. 2013 ; Vol. 2013.
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