Caspase activation during phorbol ester-induced apoptosis requires ROCK-dependent myosin-mediated contraction

Jin Mei Lai, Chia Ling Hsieh, Zee Fen Chang

研究成果: 雜誌貢獻文章

63 引文 斯高帕斯(Scopus)

摘要

Treatment of cells with phorbol ester, phorbol-12-myristate-13-acetate (PMA), triggers differentiation or apoptosis, depending on the cell type. In this study, we used an erythroblastic cell line, TF-1, to investigate the molecular mechanism that determines the cell fate in response to PMA exposure. Upon PMA treatment in the presence of serum or lysophosphatidic acid (LPA), TF-1 cells exhibited contraction followed by apoptosis. By contrast, under serum-free conditions, cells became adherent and survived after PMA treatment. Here, we show that the pathway of Rho kinase (ROCK)/myosin light chain (MLC) phosphorylation/myosin-mediated contraction was activated in PMA-induced apoptotic cells in serum-containing medium, but not in the adherent and survived cells. Pretreatment of cells with a specific ROCK inhibitor, Y27632, not only abrogated MLC phosphorylation and membrane contraction, but also prevented PMA-induced activation of caspase-3 and subsequent cell death, indicating that ROCK-dependent myosin-mediated contraction elicits an upstream signal required for caspase-3 activation in PMA-induced apoptosis. Interestingly, we further found that caspases-8 and -10 are the initiator caspases in PMA-induced apoptosis and a ROCK-dependent enhancement of specific complex formation between the Fas-associated death domain (FADD) and pro-caspase-10 in pro-apoptotic cells. In summary, these results revealed that, following PMA treatment, the upregulation of the RhoA/ROCK pathway contributes to a cellular context that switches-on myosin-mediated contraction, which provides a mechanism for triggering apoptotic induction mediated by caspase-8 and -10.
原文英語
頁(從 - 到)3491-3501
頁數11
期刊Journal of Cell Science
116
發行號17
DOIs
出版狀態已發佈 - 九月 1 2003
對外發佈Yes

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ASJC Scopus subject areas

  • Cell Biology

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