Abstract
The effects of α-tocopherol with shortened to 6 carbon atoms side chain (α-Toc-C6), α-tocopherol succinate (α-TS) and quinonimine 2,6-dichlorophenolindophenol (DCPIP) on DT-diaphorase activity and viability of rat thymocytes, splenocytes and hepatocytes were investigated. It was shown that the lowest basal activity of the enzyme is inherent in splenocytes. In comparison to splenocytes, DT-diaphorase activity was 1.4 and 5 times higher in thymocytes and hepatocytes, respectively. It was found that the sensitivity of cells to the cytotoxic effect of DCPIP was inversely proportional to the basal level of DT-diaphorase activity and accompanied by its activation with subsequent inhibition at non-toxic and toxic concentrations, respectively. Hepatocytes were least sensitive to the cytotoxic effect of α-Toc-C6. In thymocytes and splenocytes α-Toc-C6 exerts inhibitory effects on DT-diaphorase, whereas in hepatocytes an increased activity of the enzyme was observed, which probably caused their high survival rate. Simultaneous induction of cytochrome P450 enzyme expression by α-Toc-C6 in hepatocytes is also possible. Cytotoxic effect of α-TS does not depend on the basal level of DT-diaphorase activity in cells, is not accompanied by its induction and it is most likely determined by the non-specific esterase activity.
Highlights
NAD(P)H:quinone oxidoreductase 1 (DT-diaphorase, NQO1, 1.6.99.2) is a homodimeric cytosolic flavoprotein
We have previously found that the reduction of the rat thymocytes viability upon the presence of α-tocopherol with a side chain shortened to 6 carbon atoms (α-Toc-C6) and α-tocopherol succinate (α-TS) is accompanied by proteolytic degradation of the molecule of DTdiaphorase [6]
The aim of this work was a comparative study of the ability of quinonimine and synthetic derivatives of α-tocopherol (α-TP) to induce the death of cells of various origins, differing in the basal levels of DT- diaphorase activity
Summary
NAD(P)H:quinone oxidoreductase 1 (DT-diaphorase, NQO1, 1.6.99.2) is a homodimeric cytosolic flavoprotein It is involved in at least three systems of biochemical pathways, that is, single-step two-electron reduction of quinones to hydroquinones (without formation of intermediate toxic semiquinone), maintenance of endogenous antioxidants in reduced active form, regulation of the stability of the tumor suppressor and pro-apoptotic p53 factor. Participation of DT-diaphorase in various biochemical pathways, which support cell homeostasis, determined the search for compounds which biological effects are mediated by modulation of the enzyme activity These compounds may include components of natural vitamin E and synthetic tocopherol derivatives, which exhibit pro-apoptotic ef-. The aim of this work was a comparative study of the ability of quinonimine and synthetic derivatives of α-tocopherol (α-TP) to induce the death of cells of various origins, differing in the basal levels of DT- diaphorase activity
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