An Ergosterol Peroxide, a Natural Product That Selectively Enhances the Inhibitory Effect of Linoleic Acid on DNA Polymerase β

• Published in: Biological & pharmaceutical bulletin Vol. 21; no. 5; pp. 444 - 448
• Main Authors: MIZUSHINA, Yoshiyuki, WATANABE, Itiro, TOGASHI, Hideaki, HANASHIMA, Linda, TAKEMURA, Masaharu, OHTA, Keisuke, SUGAWARA, Fumio, KOSHINO, Hiroyuki, ESUMI, Yasuaki, UZAWA, Jun, MATSUKAGE, Akio, YOSHIDA, Shonen, SAKAGUCHI, Kengo
• Format: Journal Article
• Language: English
• Published: Tokyo The Pharmaceutical Society of Japan 01.05.1998; Maruzen
• Subjects: Analytical, structural and metabolic biochemistry; Animals; basidiomycete; Basidiomycota - enzymology; Biological and medical sciences; Cattle; Chromatography, High Pressure Liquid; DNA polymerase; DNA Polymerase beta - antagonists & inhibitors; DNA Polymerase I - antagonists & inhibitors; Drug Synergism; enzyme inhibitor; Enzyme Inhibitors - pharmacology; Enzymes and enzyme inhibitors; Ergosterol - analogs & derivatives; Ergosterol - pharmacology; ergosterol peroxide; Fatty Acids - chemistry; Fatty Acids - metabolism; Fundamental and applied biological sciences. Psychology; Ganoderma lucidum; linoleic acid; Linoleic Acid - pharmacology; Rats; Transferases; Fungi; Ergosterol; Nucleotidyltransferases; Microbial origin; Enzyme; Transferases; Enzyme inhibitor; Basidiomycetes; Peroxides; Ganoderma; DNA-directed DNA polymerase; Thallophyta
• ISSN: 0918-6158; 1347-5215
• DOI: 10.1248/bpb.21.444

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-5α, 8α-ergosta-6, 22E-dien-3β-ol by spectroscopic analyses. The ergosterol peroxide (EPO) itself scarcely inhibited the activities of calf thymus DNA polymerase α(pol. α) or rat DNA polymerase β(pol. β). However, when EPO at 0.25 mM was present, 10 μM or less of LA almost completely inhibited the pol. β activity, while almost complete inhibition by LA itself was acheived at 80 μM or higher. Interestingly, under the same conditions, EPO did not affect the LA-effect on pol. α. The action mode of the EPO was discussed.