Abrogation of neutral cholesterol ester hydrolytic activity causes adrenal enlargement
Abrogation of neutral cholesterol ester hydrolytic activity causes adrenal enlargement
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DOI：
10.1016/j.bbrc.2010.11.103
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发表时间：
2011-01-07
影响因子：
3.1
通讯作者：
Osuga, Jun-ichi
中科院分区：
文献类型：
--
作者：
Ohta, Keisuke;Sekiya, Motohiro;Osuga, Jun-ichi
我们之前已经证明，中性胆固醇酯水解酶1（Nceh1）通过胆固醇酯水解的催化活性调节泡沫细胞形成和动脉粥样硬化形成，并且Nceh1和激素敏感脂肪酶（Lipe）负责巨噬细胞中大部分中性胆固醇酯水解酶活性。除巨噬细胞外，还有几种胆固醇酯代谢组织和细胞，其中肾上腺皮质细胞也已知利用细胞内胆固醇进行类固醇生成。据信，细胞内胆固醇酯在肾上腺中的动员仅由 Lipe 促进。我们在此证明 Nceh1 还参与肾上腺中胆固醇酯的水解。正如先前报道的那样，Lipe 缺乏显着降低了肾上腺中的中性胆固醇酯水解酶活性，但 Nceh1 基因的额外失活完全消除了该活性。肾上腺增大与中性胆固醇酯水解酶活性降低的程度成比例，并且在Nceh1/Lipe双缺陷小鼠中，肾上腺增大和胆固醇酯积累最为明显。因此Nceh1参与肾上腺胆固醇代谢，肾上腺胆固醇酯水解活性与器官肿大相关。 (C) 2010 Elsevier Inc. 保留所有权利。
We have previously demonstrated that neutral cholesterol ester hydrolase 1 (Nceh1) regulates foam cell formation and atherogenesis through the catalytic activity of cholesterol ester hydrolysis, and that Nceh1 and hormone-sensitive lipase (Lipe) are responsible for the majority of neutral cholesterol ester hydrolase activity in macrophages. There are several cholesterol ester-metabolizing tissues and cells other than macrophages, among which adrenocortical cells are also known to utilize the intracellular cholesterol for steroidogenesis. It has been believed that the mobilization of intracellular cholesterol ester in adrenal glands was facilitated solely by Lipe. We herein demonstrate that Nceh1 is also involved in cholesterol ester hydrolysis in adrenal glands. While Lipe deficiency remarkably reduced the neutral cholesterol ester hydrolase activity in adrenal glands as previously reported, additional inactivation of Nceh1 gene completely abrogated the activity. Adrenal glands were enlarged in proportion to the degree of reduced neutral cholesterol ester hydrolase activity, and the enlargement of adrenal glands and the accumulation of cholesterol esters were most pronounced in the Nceh1/Lipe double-deficient mice. Thus Nceh1 is involved in the adrenal cholesterol metabolism, and the cholesterol ester hydrolytic activity in adrenal glands is associated with the organ enlargement. (C) 2010 Elsevier Inc. All rights reserved.