Lysophosphatidic acid-induced nuclear localization of protein kinase C δ in bovine theca cells stimulated with luteinizing hormone
Lysophosphatidic acid-induced nuclear localization of protein kinase C δ in bovine theca cells stimulated with luteinizing hormone
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DOI：
10.1095/biolreprod.101.003087
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发表时间：
2002-09-01
影响因子：
3.6
通讯作者：
Mukhopadhyay, AK
中科院分区：
文献类型：
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作者：
Budnik, LT;Mukhopadhyay, AK
溶血磷脂酶D（LPLD）和卵巢蛋白激酶C δ（PKC δ）的量在妊娠过程中增加。由于LPLD参与生物活性磷脂溶血磷脂酸（LPA）的产生，我们研究了LPA刺激是否会影响卵巢中的PKC δ。我们用免疫印迹和免疫组化方法表明，刺激牛卵泡膜细胞与LPA导致一个意想不到的重新分配的PKC δ从胞质到核周区，并在LH的存在下，LPA诱导一个完整的核转位的PKC δ。LPA的这些作用是剂量依赖性的，可以被佛波酯模拟，并被PKC δ抑制剂rottlerin抑制。同时，在相同的实验条件下，LPA和佛波酯PMA（4 β-佛波醇-12-肉豆蔻酸酯-13-乙酸酯）增加LH刺激的孕酮在该细胞系统中的积累。LPA和PMA的这种功能作用在用rottlerin预处理的细胞中被消除。目前尚不清楚PKC δ的核定位是否表明该酶在牛卵巢中的特定功能。由于PKC δ在啮齿动物模型中支持促黄体功能，因此在牛卵巢中也可能具有类似的作用。
The amounts of lysophospholipase D (LPLD) and the ovarian protein kinase C delta (PKCdelta) increase during the course of pregnancy. Because LPLD is involved in the production of the bioactive phospholipid lysophosphatidic acid (LPA), we examined whether stimulation with LPA would influence PKCdelta in the ovary. We used immunoblotting and immunohistochemical methods to show that stimulation of bovine theca cells with LPA leads to an unexpected redistribution of PKCdelta from the cytosol to the perinuclear area and that in the presence of LH, LPA induces a complete nuclear translocation of PKCdelta. These effects of LPA are dose dependent, can be mimicked by phorbol ester, and are inhibited by a PKCdelta inhibitor, rottlerin. Concomitantly, under the same experimental conditions both LPA and the phorbol ester PMA (4beta-phorbol-12-myristate-13-acetate) augment LH-stimulated progesterone accumulation in this cell system. This functional effect of LPA and PMA is abolished in cells pretreated with rottlerin. It is unclear whether the nuclear localization of PKCdelta indicates a specific function of the enzyme in the bovine ovary. Because PKCdelta supports a luteotropic function in rodent models, a similar role in the bovine ovary is also likely.