PKC mediates 12(S)-HETE-induced cytoskeletal rearrangement in B16a melanoma cells.
PKC mediates 12(S)-HETE-induced cytoskeletal rearrangement in B16a melanoma cells.
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PKC 介导 B16a 黑色素瘤细胞中 12(S)-HETE 诱导的细胞骨架重排。
DOI：
10.1002/cm.970260106
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发表时间：
1993
影响因子：
--
通讯作者：
Honn,KV
中科院分区：
文献类型：
--
作者：
Timar,J;Tang,D;Bazaz,R;Haddad,MM;Kimler,VA;Taylor,JD;Honn,KV
脂肪酸12(S)‐HETE可能是能够激活PKC的新的第二信使。在肿瘤细胞中，12(S)‐HETE刺激细胞骨架依赖性细胞反应，如粘附和扩散。分析12(S)‐HETE对B16a黑色素瘤细胞骨架的影响，发现微管、微丝、肌动蛋白结合蛋白、血管蛋白、肌球蛋白重链（MHC）和轻链（MLC）的可逆重排，以及静脉蛋白中间丝的捆绑。肿瘤细胞暴露于12(S)‐HETE后5分钟，微丝和中间丝的改变发生得非常快。12(S)‐HETE诱导的细胞骨架改变伴随着离心细胞器易位。有趣的是，MLC与细胞器有明显的联系。12(S)‐HETE效应的生化分析表明PKC介导的MLC、vimentin和130kd细胞骨架相关蛋白的可逆过磷酸化。0.1 μM浓度的12(S)‐HETE处理5 min后效果最佳。12(S)‐HETE预处理诱导肿瘤细胞在纤维连接蛋白基质上扩散，这需要所有三种主要细胞骨架成分的完整性。扩散过程依赖于PKC的活性。我们的数据表明，12(S)‐HETE是PKC的生理刺激物。此外，它诱导肿瘤细胞间期细胞骨架的重排，从而刺激细胞骨架依赖的细胞活性，如扩散。©1993 Wiley‐Liss, Inc。
The fatty acid 12(S)‐HETE may be a new second messenger capable of activating PKC. In tumor cells 12(S)‐HETE stimulates cytoskeleton‐dependent cellular responses such as adhesion and spreading. Analysis of 12(S)‐HETE effects on B16a melanoma cell cytoskeleton revealed reversible rearrangement of microtubules, microfilaments, the actin‐binding proteins, vinculin, myosin heavy (MHC) and light chains (MLC), as well as bundling of vimentin intermediate filaments. The alterations in microfilaments and intermediate filaments occurred very rapidly, i.e., 5 min after exposure of tumor cells to 12(S)‐HETE. The 12(S)‐HETE‐induced cytoskeletal alterations were accompanied by centrifugal organelle‐translocation. Interestingly, MLC exhibited clear association with the cytoplasmic organelles. Biochemical analysis of the 12(S)‐HETE effect indicated a PKC‐mediated reversible hyperphosphorylation of MLC, vimentin, and a 130 kD cytoskeletal‐associated protein. Optimal effects were obtained after 5 min treatment with 12(S)‐HETE at 0.1 μM concentration. 12(S)‐HETE pretreatment induced tumor cell spreading on a fibronectin matrix which required the intactness of all three major cytoskeletal components. The spreading process was dependent upon the activity of PKC. Our data suggest that 12(S)‐HETE is a physiological stimulant of PKC. Further, it induces rearrangement of the cytoskeleton of tumor cells in interphase resulting in the stimulation of cytoskeleton‐dependent cell activity such as spreading. © 1993 Wiley‐Liss, Inc.