Concomitant induction of cytosolic but not microsomal epoxide hydrolase with peroxisomal beta-oxidation by various hypolipidemic compounds.
Concomitant induction of cytosolic but not microsomal epoxide hydrolase with peroxisomal beta-oxidation by various hypolipidemic compounds.
复制标题
各种降血脂化合物同时诱导细胞质环氧化物水解酶，但不诱导微粒体环氧化物水解酶和过氧化物酶体β-氧化。
DOI：
10.1016/0006-2952(87)90292-9
复制
发表时间：
1987
影响因子：
5.8
通讯作者：
F. Oesch
中科院分区：
文献类型：
--
作者：
L. Schladt;R. Hartmann;C. Timms;M. Strolin‐Benedetti;P. Dostert;W. Wörner;F. Oesch
两种降胆固醇药物（probucol和1-苄基咪唑）、三种甘油三酯和降胆固醇药物（clofibrate）的效果研究了一种降甘油三酯（乙酰水杨酸）化合物对雄性Fischer F-344大鼠肝脏两种脂质代谢酶（氰化物不敏感的过氧化物酶体β-氧化酶和棕榈酰辅酶a水解酶）和两种外生代谢酶（胞质酶（cEH）和微粒体环氧化物水解酶（mEHb））的比活性的影响。除普罗布考和乙酰水杨酸外，所有化合物均引起剂量依赖性肝肿大。以体重为基础，非诺贝特是最有效的诱导剂，诱导过氧化物酶体β-氧化20倍，诱导cEH活性13倍，诱导棕榈酰辅酶a水解酶活性16倍。其他具有降低甘油三酯活性的化合物也能诱导cEH、过氧化物酶体β-氧化和棕榈酰辅酶a水解酶活性。与过氧化物酶体β-氧化和棕榈酰辅酶a水解酶活性相比，每种药物对cEH活性的诱导作用相似，但对mEHb的诱导作用却大不相同，任何一种降甘油三酯化合物对其的诱导作用要么没有，要么只有最低限度的（<1.5倍）。仅具有降胆固醇活性的1-苯并咪唑增加了mEHb，远高于cEH或过氧化物酶体β-氧化。体外研究没有发现cEH活性的增强，证实了测试化合物对酶活性的增强不是由活化引起的。非诺贝特、噻腺醇和乙酰水杨酸也能诱导肾脏cEH活性，但仅为2倍左右。随着降血脂药物的过氧化物酶体增殖能力从无活性到非常有效的变化，对过氧化物酶体β-氧化和cEH的影响在所有情况下都是相似的，而对mEHb的影响可以明显分离。因此，在大鼠中，降血脂药物对cEH与过氧化物酶体β-氧化和过氧化物酶体增殖的伴随调节变得明显。
The effects of two cholesterol-lowering (probucol and 1-benzyl-imidazole), three triglycerideand cholesterol-lowering (clofibrate, tiadenol and fenofibrate) and one triglyceride-lowering (acetylsalicylic acid) compounds on the specific activities of two lipid-metabolizing enzymes (cyanide-insensitive peroxisomal β-oxidation and palmitoyl-CoA hydrolase) and two xenobiotic metabolizing enzymes (cytosolic (cEH) and microsomal epoxide hydrolase (mEHb)) from the livers of male Fischer F-344 rats were investigated.With the exception of probucol and acetylsalicylic add, all compounds tested caused a dose-dependent hepatomegaly. Taken on a weight basis fenofibrate was the most effective inducer, causing a 20-fold induction of peroxisomal β-oxidation, a 13-fold induction of cEH activity and a 16-fold induction of palmitoyl-CoA hydrolase activity. The other compounds with triglyceride-lowering activity also induced cEH as well as peroxisomal β-oxidation and palmitoyl-CoA hydrolase activity. The potency of each individual drug was similar for induction of cEH activity as compared with that of peroxisomal β-oxidation and palmitoyl-CoA hydrolase activity, but very dissimilar for mEHb, which upon treatment with any of the triglyceride-lowering compounds was either not or only minimally (<1.5-fold) induced. 1-Benzylimidazole possessing exclusively cholesterol-lowering activity increased mEHb, much more than either cEH or peroxisomal β-oxidation.The absence of an enhancement of cEH activity inin vitrostudies confirmed that the increase in enzyme activity by the test compounds is not caused by activation. cEH activity was also induced in the kidney but only about 2-fold by fenofibrate, tiadenol and acetylsalicylic acid.With hypolipidemic drugs varying in their peroxisome-proliferating potency from inactive to very potent, the effects on peroxisomal β-oxidation and cEH were similar in all instances, whilst the effects on mEHb, could be clearly dissociated. Thus, in the rat a concomitant regulation of cEH with peroxisomal β-oxidation and peroxisome proliferation by hypolipidemic drugs becomes apparent.
鼠肝胞质和微粒体环氧化物水解酶的不同底物选择性。
影响因子：
5.8
作者：
Hammock,BD;Hasagawa,LS
通讯作者：
Hasagawa,LS
小鼠肝脏和肾皮质的 80 000 分子量过氧化物酶体增殖相关多肽（多肽 PPA-80）和过氧化物酶体烯酰辅酶 A 水合酶的诱导、免疫化学鉴定和免疫荧光定位。
DOI：
10.1042/bj1980177
发表时间：
1981
期刊：
The Biochemical journal
影响因子：
--
作者：
Lalwani,ND;Reddy,MK;Mangkornkanok-Mark,M;Reddy,JK
通讯作者：
Reddy,JK