Soft substrate up-regulates the interaction of STIM1 with store-operated Ca2+ channels that lead to normal epithelial cell apoptosis

研究成果: Article

30 引文 斯高帕斯(Scopus)

摘要

We have demonstrated that soft substrate induced apoptosis in polarized cells, but not in transformed cells by disturbance of Ca2+ homeostasis. This study aims to further investigate the regulatory mechanisms underlying the disruption of Ca2+-signaling integrity in soft substrate-induced epithelial apoptosis. Soft substrate up-regulated the store-operated Ca2+ (SOC) entry across the plasma membrane of normal cervical epithelial cells, which resulted in increased cytosolic Ca2+ levels. Concomitantly, soft substrate induced the aggregation and translocation of stromal interacting molecule 1 (STIM1) toward the cell periphery to colocalize with Orai1, an essential pore subunit of SOC channel, detected by fluorescence resonance energy transfer approach and confocal image analyses. The disturbed Ca2+ homeostasis resulted in the activation of μ-calpain, which cleaved α-spectrin, induced actin disorganization, and caused apoptosis. In contrast, soft substrate did not disturb Ca2+ homeostasis or induce apoptosis in cervical cancer cells. Chelating extracellular Ca2+ by EGTA and down-regulated SOC entry by small interfering RNA targeting STIM1 or inhibitors targeting Ca2+-binding site of calpain significantly inhibited soft substrate-induced activation of μ-calpain and epithelial cell apoptosis. Thus, soft substrate up-regulates the interaction of STIM1 with SOC channels, which results in the activation of μ-calpain and subsequently induces normal epithelial cell apoptosis.

原文English
頁(從 - 到)2220-2230
頁數11
期刊Molecular Biology of the Cell
19
發行號5
DOIs
出版狀態Published - 2008 五月 1

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Cell Biology

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