An ergosterol peroxide, a natural product that selectively enhances the inhibitory effect of linoleic acid on DNA polymerase beta.
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.
Mizushina
Y
Y
Department of Applied Biological Science, Science University of Tokyo, Chiba, Japan.
Watanabe
I
I
Togashi
H
H
Hanashima
L
L
Takemura
M
M
Ohta
K
K
Sugawara
F
F
Koshino
H
H
Esumi
Y
Y
Uzawa
J
J
Matsukage
A
A
Yoshida
S
S
Sakaguchi
K
K
D000818:Animals; D001487:Basidiomycota / Q000201:enzymology; D002417:Cattle; D002851:Chromatography, High Pressure Liquid; D004256:DNA Polymerase I / Q000037:antagonists & inhibitors; D019951:DNA Polymerase beta / Q000037:antagonists & inhibitors*; D004357:Drug Synergism; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D004875:Ergosterol / Q000031:analogs & derivatives* / Q000494:pharmacology; D005227:Fatty Acids / Q000737:chemistry / Q000378:metabolism; D019787:Linoleic Acid / Q000494:pharmacology*; D051381:Rats
D004791:Enzyme Inhibitors; D005227:Fatty Acids; D019787:Linoleic Acid; D004256:DNA Polymerase I; D019951:DNA Polymerase beta; C036071:ergosterol-5,8-peroxide; D004875:Ergosterol