An ergosterol peroxide, a natural product that selectively enhances the inhibitory effect of linoleic acid on DNA polymerase beta

Biological & Pharmaceutical Bulletin
Yoshiyuki MizushinaKengo Sakaguchi

Abstract

As described previously (Mizushina Y., Tanaka N., Yagi H., Kurosawa T., Onoue M., Seto H., Horie T., Aoyagi N., Yamaoka M., Matsukage A., Yoshida S., and Sakaguchi K., Biochim. Biophys. Acta, 1308, 256-262, 1996), linoleic acid (LA) inhibits the activities of mammalian DNA polymerases. We found a natural product from a basidiomycete, Ganoderma lucidum, that enhances this effect of LA in a special manner. The structure was identified to be an ergosterol peroxide, 5,8-epidioxy-5alpha,8alpha-ergosta-6,22E-dien -3beta-ol by spectroscopic analyses. The ergosterol peroxide (EPO) itself scarcely inhibited the activities of calf thymus DNA polymerase alpha (pol. alpha) or rat DNA polymerase beta (pol. beta). However, when EPO at 0.25 mM was present, 10 microM or less of LA almost completely inhibited the pol. beta activity, while almost complete inhibition by LA itself was achieved at 80 microM or higher. Interestingly, under the same conditions, EPO did not affect the LA-effect on pol. alpha. The action mode of the EPO was discussed.

Citations

May 30, 2014·The American Journal of Chinese Medicine·Chao-Yun WangChun-Hua Wang
Mar 16, 2000·Food and Chemical Toxicology : an International Journal Published for the British Industrial Biological Research Association·S W ChiuD Moore
May 9, 2012·Drug Discovery Today·Khaled H BarakatJack A Tuszynski
Aug 15, 2006·Phytochemistry·R Russell M Paterson
Dec 12, 2003·Integrative Cancer Therapies·Geoffrey A Cordell
Sep 25, 2019·Biomolecules·Thuluz Meza-MenchacaÁngel Trigos
Jan 25, 2005·Bioscience, Biotechnology, and Biochemistry·Toshiyuki TakeiMasuko Kobori
Apr 23, 2003·Biochemical and Biophysical Research Communications·Yoshiyuki MizushinaKengo Sakaguchi
Jul 26, 2005·Journal of Natural Products·Georges MassiotCatherine Lavaud

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