Phorbol ester increases mitochondrial cholesterol content in NCI H295R cells
Phorbol ester increases mitochondrial cholesterol content in NCI H295R cells
复制标题
DOI：
10.1016/j.mce.2008.08.022
复制
发表时间：
2008-12-16
影响因子：
4.1
通讯作者：
Calle, Roberto A.
中科院分区：
文献类型：
--
作者：
Bollag, Wendy B.;Kent, Patricia;Calle, Roberto A.
甾体生成的第一步是将胆固醇从胞质脂滴动员到位于线粒体内膜上的起始限速酶复合体。血管紧张素II （AngII）是肾上腺肾小球细胞分泌醛固酮的主要激动剂，已知可诱导胆固醇向线粒体动员。然而，蛋白激酶C （PKC）途径在介导胆固醇动员中的作用尚不清楚。为了确定PKC是否参与其中，将人肾上腺皮质癌细胞与PKC激活的phorbol 12-肉豆酸13-乙酸酯（PMA）孵育，并测定线粒体胆固醇含量。与AngII一样，PMA显著提高线粒体胆固醇含量和醛固酮分泌。因此，PKC可能在胆固醇动员到线粒体中发挥作用，从而产生类固醇。心房利钠肽（ANP）抑制AngII-和pma刺激的线粒体胆固醇含量。这些发现表明ANP抑制多种药物诱导的类固醇生成的能力可能与其降低胆固醇动员的能力有关。爱思唯尔爱尔兰有限公司出版。
The first step in steroidogenesis is cholesterol mobilization from cytosolic lipid droplets to the initiating rate-limiting enzyme complex located on the inner mitochondrial membrane. Angiotensin II (AngII), the primary agonist of aldosterone secretion from adrenal glomerulosa cells, is known to induce cholesterol mobilization to mitochondria. However, the role of the protein kinase C (PKC) pathway in mediating cholesterol mobilization is unknown. To determine PKC's involvement, human adrenocortical carcinoma cells were incubated with or without PKC-activating phorbol 12-myristate 13-acetate (PMA) and mitochondrial cholesterol content assayed. Like AngII, PMA significantly elevated mitocliondrial cholesterol content as well as aldosterone secretion. Thus, PKC may play a role in cholesterol mobilization to mitochondria and hence steroid production. Atrial natriuretic peptide (ANP) inhibited both AngII- and PMA-stimulated mitochondrial cholesterol content. These findings suggest that the ability of ANP to inhibit steroidogenesis induced by multiple agents may be related to its capacity to reduce cholesterol mobilization. Published by Elsevier Ireland Ltd.