Role of endoplasmic reticulum oxidase 1α in H9C2 cardiomyocytes following hypoxia/reoxygenation injury

Lai,Lina; Liu,Yue; Liu,Yuanyuan; Zhang,Ni; Cao,Shilu; Zhang,Xiaojing; Wu,Di

doi:10.3892/mmr.2020.11217

Role of endoplasmic reticulum oxidase 1α in H9C2 cardiomyocytes following hypoxia/reoxygenation injury

Authors:
- Lina Lai
- Yue Liu
- Yuanyuan Liu
- Ni Zhang
- Shilu Cao
- Xiaojing Zhang
- Di Wu
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Affiliations: Department of Pharmacology, Changzhi Medical College, Changzhi, Shanxi 046000, P.R. China, Department of Clinical Medicine, Changzhi Medical College, Changzhi, Shanxi 046000, P.R. China, Department of Surgery, University of Virginia, Charlottesville, VA 22908, USA
Published online on: June 9, 2020 https://doi.org/10.3892/mmr.2020.11217
Pages: 1420-1428
Copyright: © Lai et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Endoplasmic reticulum (ER) oxidase 1α (ERO1α) is a glycosylated flavoenzyme that is located on the luminal side of the ER membrane, which serves an important role in catalyzing the formation of protein disulfide bonds and ER redox homeostasis. However, the role of ERO1α in myocardial hypoxia/reoxygenation (H/R) injury remains largely unknown. In the present study, ERO1α expression levels in H9C2 cardiomyocytes increased following H/R, reaching their highest levels following 3 h of hypoxia and 6 h of reoxygenation. In addition, H/R induced apoptosis, and significantly increased expression levels of ER stress (ERS) markers 78 kDa glucose‑regulated protein and C/EBP homologous protein. Moreover, the genetic knockdown of ERO1α using short hairpin RNA suppressed cell apoptosis, caspase‑3 activity, expression levels of cleaved caspase‑12 and cytochrome c in the cytoplasm. Overall, this suggested that ERO1α knockdown may protect against H/R injury. The ERS activator tunicamycin (TM) was used to counteract the ERO1α‑induced reduction in ERS; however, the percentage of apoptotic cells and the level of mitochondrial damage did not change. In conclusion, the results from the present study suggested that ERO1α knockdown may protect H9C2 cardiomyocytes from H/R injury through inhibiting intracellular ROS production and increasing intracellular levels of Ca2+, suggesting that ERO1α may serve an important role in H/R.

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