Effect of 13-hydroperoxyoctadecadienoic acid on 15-hydroxy prostaglandin dehydrogenase activity in rabbit kidney cortex.
The effect of a hydroperoxy adduct of linoleic acid, 13-hydroperoxyoctadecadienoic acid (13-HPODE), on 15-hydroxy prostaglandin dehydrogenase activity in rabbit kidney cortex was examined. 13-HPODE inhibited the 15-hydroxy prostaglandin dehydrogenase activity at concentrations ranging from 1 to 10 microM. The effect was concentration-dependent and the concentration required for 50% inhibition was approximately 3 microM. Linoleic acid and 13-hydroxyoctadecadienoic acid (13-HODE) exhibited weaker inhibition of the enzyme activity than did 13-HPODE (linoleic acid, 30% inhibition at 10 microM; 13-HODE, 45% inhibition at 10 microM). Studies utilizing Fe2+ (a catalyst of peroxide decomposition), and mannitol or dimethylsulfoxide (a hydroxy radical scavenger) revealed that the inhibitory effect of 13-HPODE on the 15-hydroxy prostaglandin dehydrogenase activity is not due to the hydroxy radicals which are expected to be formed from 13-HPODE and that the hydroperoxy functional group is a prerequisite. The inhibition by 13-HPODE was uncompetitive and non-competitive with regard to NAD+ and prostaglandin E2, respectively. These results suggest that 13-HPODE has the potential to modulate the prostaglandin catabolism by affecting the 15-hydroxy prostaglandin dehydrogenase activity.
Sakuma
S
S
Department of Hygienic Chemistry, Osaka University of Pharmaceutical Sciences, Japan.
Fujimoto
Y
Y
Nakagawa
H
H
Hachiki
S
S
Nishida
H
H
Fujita
T
T
D000818:Animals; D004121:Dimethyl Sulfoxide / Q000494:pharmacology; D005296:Ferrous Compounds / Q000494:pharmacology; D006911:Hydroxyprostaglandin Dehydrogenases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D007672:Kidney Cortex / Q000187:drug effects / Q000201:enzymology*; D019787:Linoleic Acid; D008041:Linoleic Acids / Q000494:pharmacology*; D008054:Lipid Peroxides; D008297:Male; D008353:Mannitol / Q000494:pharmacology; D011817:Rabbits
D005296:Ferrous Compounds; D008041:Linoleic Acids; D008054:Lipid Peroxides; C038649:13-hydroperoxy-9,11-octadecadienoic acid; D008353:Mannitol; D019787:Linoleic Acid; D006911:Hydroxyprostaglandin Dehydrogenases; C035859:15-hydroxyprostaglandin dehydrogenase; D004121:Dimethyl Sulfoxide