Soft substrate upregulates the interaction of STIM1 with store-operated Ca channels that leads to normal epithelial cell apoptosis
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چکیده
We have demonstrated that soft substrate induced apoptosis in polarized cells, but not in transformed cells by disturbance of Ca homeostasis. This study aims to further investigate the regulatory mechanisms underlying the disruption of Ca-signaling integrity in soft substrate-induced epithelial apoptosis. Soft substrate upregulated the store-operated Ca (SOC) entry across the plasma membrane of normal cervical epithelial cells, which resulted in increased cytosolic Ca levels. Concomitantly, soft substrate induced the aggregation and translocation of stromal interacting molecule 1 (STIM1) toward the cell periphery to co-localize with Orai1, an essential pore subunit of SOC channel, detected by fluorescence resonance energy transfer approach and confocal image analyses. The disturbed Ca 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 Ca homeostasis or induce apoptosis in cervical cancer cells. Chelating extracellular Ca by EGTA, downregulated SOC entry by small interfering RNA targeting STIM1 or inhibitors targeting Ca-binding site of calpain significantly inhibited soft substrate-induced activation of μ-calpain and epithelial cell apoptosis. Thus, soft substrate upregulates the interaction of STIM1 with SOC channels that results in the activation of μ-calpain and subsequently induces normal epithelial cell apoptosis.
منابع مشابه
Soft substrate up-regulates the interaction of STIM1 with store-operated Ca2+ channels that lead to normal epithelial cell apoptosis.
We have demonstrated that soft substrate induced apoptosis in polarized cells, but not in transformed cells by disturbance of Ca(2+) homeostasis. This study aims to further investigate the regulatory mechanisms underlying the disruption of Ca(2+)-signaling integrity in soft substrate-induced epithelial apoptosis. Soft substrate up-regulated the store-operated Ca(2+) (SOC) entry across the plasm...
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تاریخ انتشار 2008