Cholesterol 7 alpha-hydroxylase is up-regulated by the competitive inhibitor 7-oxocholesterol in rat liver.
Cholesterol 7 alpha-hydroxylase is up-regulated by the competitive inhibitor 7-oxocholesterol in rat liver.
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大鼠肝脏中胆固醇 7 α-羟化酶被竞争性抑制剂 7-氧代胆固醇上调。
DOI：
10.1111/j.1432-1033.1993.tb18082.x
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发表时间：
1993
期刊：
影响因子：
--
通讯作者：
Björkhem,I
中科院分区：
文献类型：
--
作者：
Breuer,O;Sudjana-Sugiaman,E;Eggertsen,G;Chiang,JY;Björkhem,I
将Sprague‐Dawley菌株的大鼠静脉注射含有7‐氧胆固醇的脂肪乳剂（Intralipid，瑞典乌普萨拉Kabi Pharmacia的商标）。与对照组相比，这导致肝微粒体中胆固醇7α‐羟化酶活性增加，并伴有胆固醇7α‐羟化酶mRNA和微粒体胆固醇7α‐羟化酶蛋白水平升高。大鼠也被喂食补充胆甾胺的饮食，并注入7 -氧胆固醇。这些动物粪便中胆汁酸的排泄量约为抑胆胺对照组的一半。在正常大鼠的肝微粒体中添加7 -氧胆固醇，其量与7 -氧胆固醇处理大鼠的微粒体中添加的量相当，可抑制胆固醇7α -羟化酶活性约75%。当添加到纯化的细菌表达的胆固醇7α‐羟化酶（P‐450c72-24）时，胆固醇诱导了I型结合谱。7‐氧化胆固醇竞争性地抑制胆固醇结合谱，而7β‐羟胆固醇不干扰胆固醇与酶的结合。结论是，使用竞争性抑制剂7‐氧化胆固醇治疗导致胆汁酸生物合成减少，并且由于胆汁酸抑制减少，胆固醇7‐羟化酶合成代偿性增加。在7 -氧胆固醇处理大鼠的微粒体制剂中测量到的高酶活性可能是由于7 -氧胆固醇持续转化为低抑制性代谢物，例如7β -羟基胆固醇。后一种化合物在7‐氧胆固醇处理的大鼠肝微粒体中发现了高浓度。这些结果的生理学重要性与先前的研究结果有关，即7 -氧胆固醇在胆固醇喂养后在肝脏中积累，7 -氧胆固醇是在脂质过氧化过程中由胆固醇形成的。
Rats of the Sprague‐Dawley strain were infused intravenously with a fat emulsion (Intralipid, trademark of Kabi Pharmacia, Uppsala, Sweden) containing 7‐oxocholesterol. This resulted in an increased cholesterol 7α‐hydroxylase activity in liver microsomes as compared to controls and was accompanied by increased levels of cholesterol 7α‐hydroxylase mRNA and microsomal cholesterol 7α‐hydroxylase protein. Rats were also fed a cholestyramine‐supplemented diet and infused with 7‐oxocholesterol. These animals excreted about half as much bile acids in faeces as cholestyraminefed controls.Addition of 7‐oxocholesterol to liver microsomes from normal rats in amounts corresponding to those present in microsomes from 7‐oxocholesterol‐treated rats inhibited the cholesterol 7α‐hydroxylase activity by about 75%.Cholesterol induced a type‐I binding spectrum when added to a purified bacterial‐expressed cholesterol 7α‐hydroxylase (P‐450c72–24). 7‐Oxocholesterol competitively inhibited the cholesterol binding spectrum, while 7β‐hydroxycholesterol did not interfere with binding of cholesterol to the enzyme.It is concluded that treatment with the competitive inhibitor 7‐oxocholesterol leads to a reduced bile acid biosynthesis and, as a consequence of reduced bile acid inhibition, a compensatory increase in cholesterol 7α‐hydroxylase synthesis. The high enzyme activity measured in microsomal preparations from 7‐oxocholesterol‐treated rats may be due to a continuous conversion of 7‐oxocholesterol into less inhibitory metabolites, e.g. 7β‐hydroxycholesterol. The latter compound was found in high concentrations in liver microsomes from rats treated with 7‐oxocholesterol.The physiological importance of these results is discussed in relation to the previous findings that 7‐oxocholesterol is accumulated in liver after cholesterol feeding and that 7‐oxocholesterol is formed from cholesterol during lipid peroxidation.
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大鼠肝微粒体胆固醇 7 α-羟化酶 cDNA 的分子克隆。
影响因子：
3.5
作者：
M. Noshiro;M. Nishimoto;K. Morohashi;K. Okuda
通讯作者：
K. Okuda
DOI：
10.1016/s0021-9258(19)38775-7
发表时间：
1990-06
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
M. Noshiro;M. Nishimoto;K. Okuda
通讯作者：
M. Noshiro;M. Nishimoto;K. Okuda
DOI：
10.1016/s0021-9258(19)39677-2
发表时间：
1990-03
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
J. Chiang;W. F. Miller;G. Lin
通讯作者：
J. Chiang;W. F. Miller;G. Lin
3-β-羟基胆甾醇-5-en-7-酮和胆甾醇-5-烯-3-β、7-β-二醇的形成和代谢。
DOI：
10.3891/acta.chem.scand.22-1595
发表时间：
1968
期刊：
Acta chemica Scandinavica
影响因子：
--
作者：
I. Björkhem;K. Einarsson;G. Johansson
通讯作者：
G. Johansson
DOI：
10.1016/s0021-9258(18)54980-2
发表时间：
1991-10
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Y. Li;J. Chiang
通讯作者：
Y. Li;J. Chiang