High-mobility group box 1 (HMGB1) exhibits various functions according to its subcellular location, which is finely conditioned by diverse post-translational modifications, such as acetylation. The nuclear HMGB1 may prevent from cardiac hypertrophy, whereas its exogenous protein is proven to induce hypertrophic response. This present study sought to investigate the regulatory relationships between poly(ADP-ribose) polymerase 1 (PARP1) and HMGB1 in the process of pathological myocardial hypertrophy. Primary-cultured neonatal rat cardiomyocytes (NRCMs) were respectively incubated with three cardiac hypertrophic stimulants, including angiotensin II (Ang II), phenylephrine (PE), and isoproterenol (ISO), and cell surface area and the mRNA expression of hypertrophic biomarkers were measured. the catalytic activity of PARP1 was remarkably enhanced, meanwhile HMGB1 excluded from the nucleus. PARP1 overexpression by infecting with adenovirus PARP1 (Ad-PARP1) promoted the nuclear export of HMGB1, facilitated its secretion outside the cell, aggravated cardiomyocyte hypertrophy, which could be alleviated by HMGB1 overexpression. PE treatment led to the similar results, while that effect was widely depressed by PARP1 silencing or its specific inhibitor AG14361. Moreover, SD rats were intraperitoneally injected with 3-aminobenzamide (3AB, 20 mg/kg every day, a well-established PARP1 inhibitor) 7 days after abdominal aortic constriction (AAC) surgery for 6 weeks, echocardiography and morphometry of the hearts were measured. Pre-treatment of 3AB relieved AAC-caused the translocation of nuclear HMGB1 protein, cardiac hypertrophy, and heart dysfunction. Our research offers a novel evidence that PARP1 combines with HMGB1 and accelerates its translocation from nucleus to cytoplasm, and the course finally causes cardiac hypertrophy.

中文翻译：

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PARP1 与 HMGB1 相互作用并促进其在病理性心肌肥厚中的核输出。

高迁移率族框 1 (HMGB1) 根据其亚细胞位置表现出各种功能，它受到多种翻译后修饰（例如乙酰化）的精细调节。核 HMGB1 可预防心脏肥大，而其外源蛋白已被证明可诱导肥大反应。本研究旨在探讨病理性心肌肥厚过程中聚（ADP-核糖）聚合酶 1 (PARP1) 和 HMGB1 之间的调节关系。将原代培养的新生大鼠心肌细胞（NRCMs）分别与血管紧张素II（Ang II）、去氧肾上腺素（PE）和异丙肾上腺素（ISO）三种心脏肥大兴奋剂一起孵育，并测量细胞表面积和肥大生物标志物的mRNA表达. PARP1的催化活性显着增强，同时 HMGB1 被排除在细胞核之外。PARP1通过感染腺病毒PARP1（Ad-PARP1）过表达促进HMGB1的核输出，促进其分泌到细胞外，加重心肌细胞肥大，HMGB1过表达可以缓解这种情况。PE 治疗导致了类似的结果，而 PARP1 沉默或其特异性抑制剂 AG14361 广泛抑制了这种效果。此外，在腹主动脉缩窄 (AAC) 手术 6 周后 7 天，SD 大鼠腹腔注射 3-氨基苯甲酰胺（3AB，每天 20 mg/kg，一种成熟的 PARP1 抑制剂），测量心脏的超声心动图和形态测量. 3AB 的预处理减轻了 AAC 引起的核 HMGB1 蛋白易位、心脏肥大和心功能不全。