BRD2 protects the rat H9C2 cardiomyocytes from hypoxia‑reoxygenation injury by targeting Nrf2/HO‑1 signaling pathway

Liu,Yingcun; Fu,Yuqing; Xue,Xin; Tang,Gang; Si,Liangyi

doi:10.3892/etm.2023.12241

BRD2 protects the rat H9C2 cardiomyocytes from hypoxia‑reoxygenation injury by targeting Nrf2/HO‑1 signaling pathway

Authors:
- Yingcun Liu
- Yuqing Fu
- Xin Xue
- Gang Tang
- Liangyi Si
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Affiliations: Department of Cardiology, The Third Affiliated Hospital, Chongqing Medical University, Chongqing 401120, P.R. China, Department of Cardiology, The Eighth Affiliated Hospital, Sun Yat‑sen University, Shenzhen, Guangdong 518000, P.R. China, Department of Cardiology, The Third Affiliated Hospital, Chongqing Medical University, Chongqing 401120, P.R. China, Department of Cardiovascular Medicine, Shapingba Hospital Affiliated to Chongqing University, Chongqing 400030, P.R. China
Published online on: October 4, 2023 https://doi.org/10.3892/etm.2023.12241
Article Number: 542
Copyright: © Liu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Myocardial ischemia‑reperfusion (I/R) injury is a common complication of acute myocardial infarction following percutaneous coronary intervention, but there are currently no effective pharmacological targets for adjuvant therapy due to a lack of knowledge of I/R injury mechanisms in cardiomyocytes. To evaluate the effects of hypoxia‑reoxygenation on the plasma proteome of cardiomyocytes and prospective therapeutic targets, five sets of H9C2 cardiomyocytes from rats were cultured under various hypoxic circumstances. Using Cell Counting Kit‑8 (CCK8) and lactose dehydrogenase (LDH) release assays, the cell viability and LDH release of H9C2 cells were analyzed. Proteome sequencing was then performed on cardiomyocytes to show the quantitative protein changes during the I/R injury process. After hypoxia/reoxygenation, bromodomain‑containing protein 2 (BRD2) expression was evaluated. After administering the BRD2 inhibitor dBET1, the expression of nuclear factor erythroid 2‑related factor 2/haem oxygenase‑1 (Nrf2/HO‑1) was identified. The results showed that in the group exposed to 4 h of hypoxia followed by 4 h of reoxygenation (H/R4), the cell survival rate was dramatically reduced, although the apoptotic rate and LDH were much higher than in the normal oxygen group. In addition, the expressions of 2,325 proteins differed considerably between these two groups, with 128 upregulated and 122 downregulated proteins being discovered in the H/R4 group. After 4 h of reoxygenation, the BRD2 expression was increased. Following the addition of dBET1 to suppress BRD2, the expression of Nrf2/HO‑1 was reduced, but the rate of apoptosis increased. In conclusion, through the Nrf2/HO‑1 signaling pathway, BRD2 protects cardiomyocytes from damage caused by hypoxia/reoxygenation. This may have implications for novel treatment targets to minimize I/R damage to the myocardium.

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