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[胆固醇氧化产物的酯化及其对巨噬细胞中胆固醇酯化速率的影响]

[Esterification of cholesterol oxidation products and their effect on the rate of cholesterol esterification in macrophages].

作者信息

Dushkin M I, Mandrikova E V, Dolgov A V

出版信息

Vopr Med Khim. 1991 May-Jun;37(3):2-5.

PMID:1949674
Abstract

Effects of cholesterol (CH) autooxidation products on incorporation of 14C-oleate into cholesteryl esters (CE) and their possible esterification were studied in cultivated mice peritoneal macrophages (MPM). 25 Mg/ml of purified CH and 25 Mg/ml of autooxidized CH stimulated (4- and 17-fold, respectively) the cholesterol esterification in MPM. In presence of 4 Mg/ml 25-hydroxy CH or the mixture of 4 Mg/ml 7 alpha-, 7 beta-hydroxy CH and 7-keto CH incorporation of oleate into cellular CE was increased 20- and 4-fold, respectively. 4 Mg/ml concentration of cholestane-3 beta, 5 alpha, 6 beta-friol caused no effects. Mono- and diesters of 14C-hydroxy CH were found after 8 hrs incubation of the steroid with MPM. Incorporation of 14C-25 hydroxy CH into its esters occurred at the rate, which exceeded 6-7-fold the 14C-CH incorporation into CE. Esterification of 7 alpha-, 7 beta-hydroxyCH and 7-ketoCH was studied, 0.52% label of the total cell sterols radioactivity was detected in the fraction of nonpolar steroids. 14C-cholestane-3 beta,5 alpha,6 beta-triol was not esterified in MPM. The stimulating effects of 25-hydroxyCH on oleate incorporation into CE and its esterification in MPM were inhibited in presence of 10 Mg/ml progesterone, an inhibitor of acyl-CoA:cholesterol acyltransferase activity. Induction of CE formation in MPM by means of choltransferase activity. Induction of CE formation in MPM by means of cholesterol oxidation products may be responsible for development of foam cells, while esterification of polar steroids in cells appears to be of importance in decrease of their toxic and metabolic effects.

摘要

在培养的小鼠腹腔巨噬细胞(MPM)中研究了胆固醇(CH)自氧化产物对14C-油酸掺入胆固醇酯(CE)及其可能的酯化作用的影响。25μg/ml的纯化CH和25μg/ml的自氧化CH分别刺激(分别为4倍和17倍)MPM中的胆固醇酯化。在存在4μg/ml 25-羟基CH或4μg/ml 7α-、7β-羟基CH与7-酮CH的混合物时,油酸掺入细胞CE分别增加了20倍和4倍。4μg/ml浓度的胆甾烷-3β,5α,6β-三醇没有作用。将该类固醇与MPM孵育8小时后,发现了14C-羟基CH的单酯和二酯。14C-25-羟基CH掺入其酯中的速率超过14C-CH掺入CE的速率6-7倍。研究了7α-、7β-羟基CH和7-酮CH的酯化,在非极性类固醇部分中检测到总细胞甾醇放射性的0.52%标记。14C-胆甾烷-3β,5α,6β-三醇在MPM中未被酯化。在存在10μg/ml孕酮(酰基辅酶A:胆固醇酰基转移酶活性抑制剂)的情况下,25-羟基CH对油酸掺入CE及其在MPM中的酯化的刺激作用受到抑制。通过胆固醇氧化产物诱导MPM中CE的形成可能是泡沫细胞形成的原因,而细胞中极性类固醇的酯化似乎对降低其毒性和代谢作用很重要。

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