Oncotarget

Research Papers:

PERK/CHOP contributes to the CGK733-induced vesicular calcium sequestration which is accompanied by non-apoptotic cell death

Yufeng Wang, Yasuhiro Kuramitsu _, Byron Baron, Takao Kitagawa, Junko Akada, Kazuhiro Tokuda, Dan Cui and Kazuyuki Nakamura

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Oncotarget. 2015; 6:25252-25265. https://doi.org/10.18632/oncotarget.4487

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Abstract

Yufeng Wang1, Yasuhiro Kuramitsu1, Byron Baron1, Takao Kitagawa1, Junko Akada1, Kazuhiro Tokuda1, Dan Cui2, Kazuyuki Nakamura1,3

1Department of Biochemistry and Functional Proteomics, Yamguchi University Graduate School of Medicine, Ube, Japan

2Department of Pathology, Yamguchi University Graduate School of Medicine, Ube, Japan

3Centre of Clinical Laboratories in Tokuyama Medical Association Hospital, Shunan, Japan

Correspondence to:

Yasuhiro Kuramitsu, e-mail: [email protected]

Keywords: CGK733, calcium sequestration, PERK/CHOP, ER stress, non-apoptotic death

Received: April 02, 2015     Accepted: June 29, 2015     Published: July 10, 2015

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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