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  • The anti-carcinogenic effect of statins in a rat model correlates with levels and synthesis of ubiquinone
    Ačimovič, Jure ...
    Ubiquinone (Q) is a product in the cholesterol synthesis pathway and is an essential component of the respiratory chain in the mitochondrial membrane. Inaddition, extra-mitochondrial Q has ... anti-oxidative properties and this fraction is increased during carcinogenesis. The aim of the present study was to investigate if extra-mitochondrial level of Q is affected by statin treatment in a rat model for liver cancer, and if this change correlates withinhibited carcinogenesis. To do this we isolated sub-cellular fractions ofrat livers from a previous experiment where we have shown anti-carcinogeniceffects of statins. The levels of Q(8), Q(9) and Q(10) were analysed with liquid chromatography-mass spectrometry. The Q(9)-levels, constituting the major part of Q in rats, were not significantly affected in any of the sub-cellular compartments. The levels of Q(10), constituting a minor part of Q in rats but the major part of Q in humans, were significantlydecreased by about 60% in the statin treated rats. The decrease was present in all sub-cellular compartments, but was most pronounced in the cytosol. There was a significant correlation between extra-mitochondrial Q(10)levels and inhibited carcinogenesis. No such correlation was observed with extra-mitochondrial Q(9). The reduced Q(10)-levels might be explained bythe reduced availability of isoprene units during statin treatment, shiftingthe synthesis towards isoforms with shorter side-chains. In line with this hypothesis there were increased levels of Q(8)-levels during statin treatment. The results support our previous suggestion that at least part of the anti-carcinogenic effect of statins in our rat model is mediated by effects on synthesis of Q. We also demonstrate a shift in the Q-synthesis pathway towards isoforms with shorter side-chains during statin treatment. (Abs. trunc. at 2000 ch.)
    Vir: Biochemical and biophysical research communications. - ISSN 0006-291X (Vol. 425, iss. 2, 2012, str. 348-352)
    Vrsta gradiva - članek, sestavni del
    Leto - 2012
    Jezik - angleški
    COBISS.SI-ID - 30074585
    DOI

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