Williams M T, Simonet L
Department of Biochemistry, College of Medicine, University of South Florida, Tampa 33612.
Toxicol Appl Pharmacol. 1988 Dec;96(3):541-9. doi: 10.1016/0041-008x(88)90013-0.
Administration of a diet containing 2.5% (w/w) griseofulvin (GF) resulted in a significant decrease in hepatic microsomal stearyl CoA desaturase activity compared to desaturase activity in microsomes from animals fed a normal rat chow diet. Desaturase activities were 0.66 +/- 0.18 vs 0.16 +/- 0.09 nmoles oleyl CoA formed/min/mg protein for control and GF-fed animals, respectively. Examination of lipid peroxides in microsomes from control and GF-treated rats showed an approximate fivefold higher concentration of lipid peroxides in microsomes from GF-treated rats compared to that from controls. However, when rats were fed a diet containing GF and diphenyl-p-phenylenediamine an inhibitor of lipid peroxidation, stearyl CoA desaturase activity was still similar to that observed with GF alone, even though microsomal lipid peroxides were reduced to nondetectable levels. In vitro stimulation of microsomal lipid peroxidation using ADP-Fe and EDTA-Fe did not result in a significant decrease in desaturase activity. Results of our experiments show that dietary administration of GF results in a marked decrease in stearyl CoA desaturase activity in hepatic microsomes. Although GF feeding stimulates microsomal lipid peroxidation, increase in microsomal peroxidation does not appear to be the mechanism by which GF feeding decreases desaturase activity. GF appears to act by decreasing the terminal desaturase activity.
与喂食正常大鼠饲料的动物微粒体中的去饱和酶活性相比，给予含2.5%（w/w）灰黄霉素（GF）的饮食会导致肝微粒体硬脂酰辅酶A去饱和酶活性显著降低。对照组和喂食GF的动物的去饱和酶活性分别为0.66±0.18和0.16±0.09纳摩尔油酸辅酶A形成/分钟/毫克蛋白质。对对照组和经GF处理的大鼠微粒体中的脂质过氧化物进行检测发现，经GF处理的大鼠微粒体中的脂质过氧化物浓度比对照组高约五倍。然而，当给大鼠喂食含GF和脂质过氧化抑制剂二苯基对苯二胺的饮食时，硬脂酰辅酶A去饱和酶活性仍与单独使用GF时观察到的相似，尽管微粒体脂质过氧化物已降至无法检测的水平。使用ADP-Fe和EDTA-Fe在体外刺激微粒体脂质过氧化并未导致去饱和酶活性显著降低。我们的实验结果表明，饮食中给予GF会导致肝微粒体中硬脂酰辅酶A去饱和酶活性显著降低。尽管喂食GF会刺激微粒体脂质过氧化，但微粒体过氧化的增加似乎不是GF喂食降低去饱和酶活性的机制。GF似乎是通过降低末端去饱和酶活性起作用的。
