Protein tyrosine phosphatases regulate arachidonic acid release, StAR induction and steroidogenesis acting on a hormone-dependent arachidonic acid-preferring acyl-CoA synthetase
Protein tyrosine phosphatases regulate arachidonic acid release, StAR induction and steroidogenesis acting on a hormone-dependent arachidonic acid-preferring acyl-CoA synthetase
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DOI：
10.1016/j.jsbmb.2006.01.003
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发表时间：
2006-06-01
影响因子：
4.1
通讯作者：
Podesta, Ernesto J.
中科院分区：
文献类型：
--
作者：
Cano, Florencia;Poderoso, Cecilia;Podesta, Ernesto J.
类固醇生物合成中限速步骤的激活，即将胆固醇转运至线粒体，依赖于 ACTH 和 LH 等激素触发的 PKA 介导的事件。其中两个事件是由蛋白酪氨酸磷酸酶 (PTP) 介导的蛋白酪氨酸去磷酸化和由两种酶 ACS4（酰基辅酶 A 合成酶 4）和 Acot2（线粒体硫酯酶）介导的花生四烯酸 (AA) 释放。 ACTH 和 LH 调节 PTP 和 Acot2 的活性并促进 ACS4 的诱导。在这里，我们分析了 PTPs 对 ACS4 表达的参与。我们发现两种 PTP 抑制剂通过不同的机制发挥作用，都能够消除激素对 ACS4 诱导的影响。 PTP 抑制剂还可以降低 cAMP 对类固醇生成和 StAR 蛋白水平的影响，从而促进胆固醇进入线粒体。此外，我们的结果表明，外源 AA 能够克服 PTP 抑制剂对 StAR 蛋白水平和类固醇生成的抑制。然后，我们在这里描述 PTP 活性和 AA 释放之间的联系，因为 ACS4 诱导受到 PTP 活性的控制，是 AA 释放、StAR 诱导和类固醇生成的关键事件。 (c) 2006 Elsevier Ltd. 保留所有权利。
The activation of the rate-limiting step in steroid biosynthesis, that is the transport of cholesterol into the mitochondria, is dependent on PKA-mediated events triggered by hormones like ACTH and LH. Two of such events are the protein tyrosine dephosphorylation mediated by protein tyrosine phosphatases (PTPs) and the release of arachidonic acid (AA) mediated by two enzymes, ACS4 (acyl-CoA synthetase 4) and Acot2 (mitochondrial thioesterase). ACTH and LH regulate the activity of PTPs and Acot2 and promote the induction of ACS4. Here we analyzed the involvement of PTPs on the expression of ACS4. We found that two PTP inhibitors, acting through different mechanisms, are both able to abrogate the hormonal effect on ACS4 induction. PTP inhibitors also reduce the effect of cAMP on steroidogenesis and on the level of StAR protein, which facilitates the access of cholesterol into the mitochondria. Moreover, our results indicate that exogenous AA is able to overcome the inhibition produced by PTP inhibitors on StAR protein level and steroidogenesis. Then, here we describe a link between PTP activity and AA release, since ACS4 induction is under the control of PTP activity, being a key event for AA release, StAR induction and steroidogenesis. (c) 2006 Elsevier Ltd. All rights reserved.