Hypoxia induces cyclophilin B through the activation of transcription factor 6 in gastric adenocarcinoma cells

Jeong,Kwon; Kim,Kiyoon; Kim,Hunsung; Oh,Yoojung; Kim,Seong‑Jin; Jo,Yunhee; Choe,Wonchae

doi:10.3892/ol.2015.3102

Hypoxia induces cyclophilin B through the activation of transcription factor 6 in gastric adenocarcinoma cells

Authors:
- Kwon Jeong
- Kiyoon Kim
- Hunsung Kim
- Yoojung Oh
- Seong‑Jin Kim
- Yunhee Jo
- Wonchae Choe
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Affiliations: Department of Biochemistry and Molecular Biology (BK21 project), Medical Research Center for Bioreaction to Reactive Oxygen Species and Biomedical Science Institute, School of Medicine, Kyung Hee University, Seoul 130‑701, Republic of Korea, Neurodegeneration Control Research Center, School of Medicine, Kyung Hee University, Seoul 130‑701, Republic of Korea
Published online on: April 7, 2015 https://doi.org/10.3892/ol.2015.3102
Pages: 2854-2858

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Abstract

Hypoxia is an important form of physiological stress that induces cell death, due to the resulting endoplasmic reticulum (ER) stress, particularly in solid tumors. Although previous studies have indicated that cyclophilin B (CypB) plays a role in ER stress, there is currently no direct information supporting the mechanism of CypB involvement under hypoxic conditions. However, it has previously been demonstrated that ER stress positively regulates the expression of CypB. In the present study, it was demonstrated that CypB is transcriptionally regulated by hypoxia‑mediated activation of transcription factor 6 (ATF6), an ER stress transcription factor. Subsequently, the effects of ATF6 on CypB promoter activity were investigated and an ATF6‑responsive region in the promoter was identified. Hypoxia and ATF6 expression each increased CypB promoter activity. Collectively, these results demonstrate that ATF6 positively regulates the expression of CypB by binding to an ATF6‑responsive region in the promoter, which may play an important role in the attenuation of apoptosis in the adaption to hypoxia. These results suggest that CypB may be a key molecule in the adaptation of cells to hypoxic conditions.

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