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-hydroperoxyoct adecadienoic acid (13-HPODE), on 15-hydroxy prostaglandin dehydrogenas e activity in rabbit kidney cortex was examined. 13-HPODE inhibited th e 15-hydroxy prostaglandin dehydrogenase activity at concentrations ra nging from 1 to 10 muM. The effect was concentration-dependent and the concentration required for 50% inhibition was approximately 3 muM. Li noleic acid and 13-hydroxyoctadecadienoic acid (13-HODE) exhibited wea ker inhibition of the enzyme activity than did 13-HPODE (linoleic acid , 30% inhibition at 10 muM; 13-HODE, 45% inhibition at 10 muM). Studie s utilizing Fe2+ (a catalyst of peroxide decomposition), and mannitol or dimethylsulfoxide (a hydroxy radical scavenger) revealed that the i nhibitory effect of 13-HPODE on the 15-hydroxy prostaglandin dehydroge nase 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-c ompetitive with regard to NAD+ and prostaglandin E2, respectively. The se results suggest that 13-HPODE has the potential to modulate the pro staglandin catabolism by affecting the 15-hydroxy prostaglandin dehydr ogenase activity.