| Author/Editor | Ačimovič, Jure; Lovgren-Sandblom, Anita; Eriksson, Lennart C; Bjorkhem-Bergman, Linda | |
| Title | The anti-carcinogenic effect of statins in a rat model correlates with levels and synthesis of ubiquinone | |
| Type | članek | |
| Source | Biochem Biophys Res Commun | |
| Vol. and No. | Letnik 425, št. 2 | |
| Publication year | 2012 | |
| Volume | str. 348-52 | |
| Language | eng | |
| Abstract | Ubiquinone (Q) is a product in the cholesterol synthesis pathway and is an essential component of the respiratory chain in the mitochondrial membrane. In addition, 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 with inhibited carcinogenesis. To do this we isolated sub-cellular fractions of rat livers from a previous experiment where we have shown anti-carcinogenic effects 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 significantly decreased 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 by the reduced availability of isoprene units during statin treatment, shifting the 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.) | |
| Descriptors | LIVER NEOPLASMS, EXPERIMENTAL UBIQUINONE HMG-COA REDUCTASE INHIBITORS CHOLESTEROL CHROMATOGRAPHY, LIQUID SPECTRUM ANALYSIS, MASS DISEASE MODELS, ANIMAL RATS, INBRED F344 |