PERK/CHOP contributes to the CGK733-induced vesicular calcium sequestration which is accompanied by non-apoptotic cell death |
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| Authors: | Yufeng Wang Yasuhiro Kuramitsu Byron Baron Takao Kitagawa Junko Akada Kazuhiro Tokuda Dan Cui Kazuyuki Nakamura |
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| Institution: | 1. Department of Biochemistry and Functional Proteomics, Yamguchi University Graduate School of Medicine, Ube, Japan;2. Department of Pathology, Yamguchi University Graduate School of Medicine, Ube, Japan;3. Centre of Clinical Laboratories in Tokuyama Medical Association Hospital, Shunan, Japan |
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| Abstract: | Calcium ions (Ca2+) are indispensable for the physiology of organisms and the molecular regulation of cells. We observed that CGK733, a synthetic chemical substance, induced non-apoptotic cell death and stimulated reversible calcium sequestration by vesicles in pancreatic cancer cells. The endoplasmic reticulum (ER) stress eukaryotic translation initiation factor 2-alpha kinase 3/C/EBP homologous protein (PERK/CHOP) signaling pathway was shown to be activated by treatment with CGK733. Ionomycin, an ER stress drug and calcium ionophore, can activate PERK/CHOP signaling and accelerate CGK733-induced calcium sequestration. Knockdown of CHOP diminished CGK733-induced vesicular calcium sequestration, but had no effects on the cell death. Proteomic analysis demonstrated that the ER-located calcium-binding proteins, calumenin and protein S100-A11, were altered in CGK733-treated cells compared to non-treated controls. Our study reveals that CGK733-induced intracellular calcium sequestration is correlated with the PERK/CHOP signaling pathway and may also be involved in the dysregulations of calcium-binding proteins. |
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| Keywords: | CGK733 calcium sequestration PERK/CHOP ER stress non-apoptotic death |
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