Protein kinase C activation is required for the lead-induced inhibition of proliferation and differentiation of cultured oligodendroglial progenitor cells
Protein kinase C activation is required for the lead-induced inhibition of proliferation and differentiation of cultured oligodendroglial progenitor cells
复制标题
DOI：
10.1016/s0006-8993(01)03385-6
复制
发表时间：
2002-03-01
期刊：
影响因子：
2.9
通讯作者：
Poretz, RD
中科院分区：
文献类型：
--
作者：
Deng, WB;Poretz, RD
铅是一种常见的神经毒物，对公众健康有重大影响。以往的研究表明，培养的少突胶质细胞前体细胞(OPC)对铅毒性非常敏感。本研究旨在探讨铅对体外培养的骨肉瘤细胞存活、增殖和分化的影响。剂量-反应研究表明，大于或等于5~10微米的铅在24小时内对OPC有细胞毒性作用，而1微米的铅可抑制OPC的增殖和分化，但不影响细胞的存活率，铅显著降低OPC的增殖能力，并抑制OPC的细胞内源性谱系进程。双吲哚马来酰亚胺1对蛋白激酶C(PKC)的抑制可消除铅诱导的细胞增殖和分化的抑制作用，而蛋白激酶C激动剂佛波醇-12，13-十二酸的作用则被铅增强。此外，铅暴露导致OPC的PKC从胞浆移位到膜上，而不增加细胞内总的PKC酶活性。这些结果表明，铅在体外抑制少突胶质细胞系细胞的增殖和分化可能是通过激活PKC来实现的。(C)2002 Elsevier Science B.V.保留所有权利。
Lead (Pb) is a common neurotoxicant of major public health concern. Previous studies revealed that cultured oligodendrocyte progenitor cells (OPCs) are highly vulnerable to Pb toxicity. The present study examines the effect of Pb on the survival, proliferation and differentiation of OPCs in vitro. Dose-response studies showed that greater than or equal to5-10 muM Pb is cytotoxic to OPCs within 24 h. However, 1 muM of Pb was found to inhibit the proliferation and differentiation of OPCs without affecting cell viability, Pb markedly decreased the proliferative capability of OPCs and inhibited cell-intrinsic lineage progression of OPCs at a late progenitor stage. The Pb-induced decrease of proliferation and differentiation was abolished by inhibition of protein kinase C (PKC) with bisindolylmaleimide 1, while the effect of the PKC-activating agent phorbol-12,13-didecanoate was potentiated by Pb. Furthermore, Pb exposure of OPCs caused the translocation of PKC from the cytoplasm to membrane without an increase in total cellular PKC enzymic activity. These results indicate that Pb inhibits the proliferation and differentiation of oligodendrocyte lineage cells in vitro through a mechanism requiring PKC activation. (C) 2002 Elsevier Science B.V. All rights reserved.