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Dexmedetomidine Preconditioning Protects Cardiomyocytes Against Hypoxia/Reoxygenation-Induced Necroptosis by Inhibiting HMGB1-Mediated Inflammation

Dexmedetomidine Preconditioning Protects Cardiomyocytes Against Hypoxia/Reoxygenation-Induced Necroptosis by Inhibiting HMGB1-Mediated Inflammation

Jingyi Chen, Zhenzhen Jiang, Xing Zhou, Xingxing Sun, Jianwei Cao, Yongpan Liu, Xianyu Wang

Cardiovasc Drugs Ther. 2019 Feb;33(1):45-54.

PMID: 30675709

Abstract:

Myocardial ischemia/reperfusion (I/R) injury is a serious threat to the health of people around the world. Recent evidence has indicated that high-mobility group box-1 (HMGB1) is involved in I/R-induced inflammation, and inflammation can cause necroptosis of cells. Interestingly, dexmedetomidine (DEX) has anti-inflammatory properties. Therefore, we speculated that DEX preconditioning may suppress H/R-induced necroptosis by inhibiting expression of HMGB1 in cardiomyocytes. We found that hypoxia/reoxygenation (H/R) significantly increased cellular damage, as measured by cell viability (100 ± 3.26% vs. 53.33 ± 3.29, p < 0.01), CK-MB (1 vs. 3.25 ± 0.26, p < 0.01), cTnI (1 vs. 2.69 ± 0.31, p < 0.01), inflammation as indicated by TNF-α (1 ± 0.09 vs. 2.57 ± 0.12, p < 0.01), IL-1β (1 ± 0.33 vs. 3.87 ± 0.41, p < 0.01) and IL-6 (1 ± 0.36 vs. 3.60 ± 0.45, p < 0.01), and necroptosis, which were accompanied by significantly increased protein levels of HMGB1. These changes [cellular damage as measured by cell viability (53.33 ± 3.29% vs. 67.59 ± 2.69%, p < 0.01), CK-MB (3.25 ± 0.26 vs. 2.27 ± 0.22, p < 0.01), cTnI (2.69 ± 0.31 vs. 1.90 ± 0.25, p < 0.01), inflammation as indicated by TNF-α (2.57 ± 0.12 vs. 1.75 ± 0.15, p < 0.01), IL-1β (3.87 ± 0.41 vs. 2.09 ± 0.36, p < 0.01) and IL-6 (3.60 ± 0.45 vs. 2.21 ± 0.39, p < 0.01), and necroptosis proteins] were inhibited by DEX preconditioning. We also found that silencing expression of HMGB1 reinforced the protective effects of DEX preconditioning and overexpression of HMGB1 counteracted the protective effects of DEX preconditioning. Thus, we concluded that DEX preconditioning inhibits H/R-induced necroptosis by inhibiting expression of HMGB1 in cardiomyocytes.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
IAR4243982	MB-3			Price

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