Sakuma S, Fujimoto Y, Nakagawa H, Hachiki S, Nishida H, Fujita T
Department of Hygienic Chemistry, Osaka University of Pharmaceutical Sciences, Japan.
Prostaglandins. 1993 Aug;46(2):157-65. doi: 10.1016/0090-6980(93)90041-5.
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.
研究了亚油酸的氢过氧化物加合物13-氢过氧化十八碳二烯酸（13-HPODE）对兔肾皮质中15-羟基前列腺素脱氢酶活性的影响。13-HPODE在1至10微摩尔的浓度范围内抑制15-羟基前列腺素脱氢酶的活性。该作用呈浓度依赖性，50%抑制所需的浓度约为3微摩尔。亚油酸和13-羟基十八碳二烯酸（13-HODE）对该酶活性的抑制作用比13-HPODE弱（亚油酸在10微摩尔时抑制30%；13-HODE在10微摩尔时抑制45%）。利用Fe2+（过氧化物分解的催化剂）以及甘露醇或二甲亚砜（羟基自由基清除剂）进行的研究表明，13-HPODE对15-羟基前列腺素脱氢酶活性的抑制作用并非源于预期由13-HPODE形成的羟基自由基，且氢过氧基官能团是一个必要条件。13-HPODE的抑制作用分别对NAD+和前列腺素E2而言是非竞争性和反竞争性的。这些结果表明，13-HPODE有可能通过影响15-羟基前列腺素脱氢酶的活性来调节前列腺素的分解代谢。
