Cardiac Nuclear High-Mobility Group Box 1 Ameliorates Pathological Cardiac Hypertrophy by Inhibiting DNA Damage Response
Cardiac Nuclear High-Mobility Group Box 1 Ameliorates Pathological Cardiac Hypertrophy by Inhibiting DNA Damage Response
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DOI：
10.1016/j.jacbts.2018.11.011
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发表时间：
2019-04-01
影响因子：
9.7
通讯作者：
Watanabe，Masafumi
中科院分区：
文献类型：
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作者：
Takahashi，Tetsuya;Shishido，Tetsuro;Watanabe，Masafumi
高迁移率组框1 （HMGB1）是一种与DNA修复相关的脱氧核糖核酸（DNA）结合蛋白。在人类衰竭心脏中，核HMGB1表达降低，DNA损伤反应（DDR）增加。与野生型小鼠相比，血管紧张素II刺激后，心脏特异性HMGB1过表达转基因小鼠的DNA损伤和DDR以及心脏重构受到抑制。在体外，抑制HMGB1可增加细胞外信号相关激酶1/2和核因子κ B的磷酸化，DDR抑制剂治疗可挽救这种磷酸化。DDR抑制剂治疗对血管紧张素ii诱导的小鼠心脏重构具有心脏保护作用。
High-mobility group box 1 (HMGB1) is a deoxyribonucleic acid (DNA)–binding protein associated with DNA repair. Decreased nuclear HMGB1 expression and increased DNA damage response (DDR) were observed in human failing hearts. DNA damage and DDR as well as cardiac remodeling were suppressed in cardiac-specific HMGB1 overexpression transgenic mice after angiotensin II stimulation as compared with wild-type mice. In vitro, inhibition of HMGB1 increased phosphorylation of extracellular signal-related kinase 1/2 and nuclear factor kappa B, which was rescued by DDR inhibitor treatment. DDR inhibitor treatment provided a cardioprotective effect on angiotensin II–induced cardiac remodeling in mice.