Activation of caspase-8 and Erk-1/2 in domes regulates cell death induced by confluence in MDCK cells

Yung Heng Chang, Hsi Hui Lin, Yang Kao Wang, Wen Tai Chiu, Hsiao Wen Su, Ming Jer Tang

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8 引文 斯高帕斯(Scopus)


Under normal culture conditions, cells adhere to culture dish, spread out, proliferate, and finally cover all areas and reach confluence. During the confluent stage, cell proliferation ceases and differentiation is enhanced. Meanwhile, cell death also appears as the monolayer confluence proceeds. To delineate the mechanism of cell death induced by the confluent process, we employed Madin-Darby canine kidney (MDCK) cells. When approaching confluence, MDCK cells exhibited increase the levels of caspase-2 and enhanced the activity of caspase-8. Using various caspase inhibitors to block apoptosis, we found that only z-VAD-fmk and z-IETD-fmk can inhibit confluent cell death, indicating that confluent cell death is mediated by activation of caspase-8. Overexpression of Bcl-2 inhibited confluent cell death, suggesting the involvement of mitochondria-dependent pathway in confluent cell death. Interestingly, the activity of phospho-Erk (p-Erk) was initially decreased before confluence, but markedly increased after confluence. Immunofluorescence staining studies showed that p-Erk was expressed exclusively on dome-forming cells that underwent apoptosis. Treatment of confluent MDCK cells with PD98059 and UO126, the inhibitors of MEK, enhanced apoptosis as well as activity of caspase-8. These data indicate that elevation of p-Erk activity during confluence may serve to suppress confluent cell death. Taken together, activation of caspase-8 contributes to and results in confluent cell death, whereas elevated p-Erk activity serves to prevent confluent cell death by regulating activation of caspase-8.

頁(從 - 到)174-182
期刊Journal of Cellular Physiology
出版狀態Published - 2007 4月

All Science Journal Classification (ASJC) codes

  • 生理學
  • 臨床生物化學
  • 細胞生物學


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