Ubc9 Attenuates Myocardial Ischemic Injury Through Accelerating Autophagic Flux

作者：Qing Xiao, Xiuhui Chen, Ru‐Chao Jiang, Sheng‐Ying Chen, Kai-Feng Chen, Xiang Zhu, Xiaoling Zhang, Junjun Huang, Yuan Qin, Guiping Zhang, Yi Quan, Jiandong Luo · 发表于：Frontiers in Pharmacology · 年份：2020 · DOI：10.3389/fphar.2020.561306 · 被引用次数：19 · 研究领域：Ubiquitin and proteasome pathways、Autophagy in Disease and Therapy、Sirtuins and Resveratrol in Medicine

Aims: SUMOylation is a post-translational modification that plays a crucial role in the cellular stress response. We aimed to demonstrate whether and how the SUMO E2 conjugation enzyme Ubc9 affects acute myocardial ischemic (MI) injury. Methods and Results: Adenovirus expressing Ubc9 was administrated by multipoint injection in the border zone of heart immediately after MI in C57BL/6 mice. Neonatal rat cardiomyocytes (NRCMs) were also infected, and oxygen and glucose deprivation (OGD) followed. In vivo, Ubc9 adenovirus-injected mice showed decreased cardiomyocyte apoptosis, reduced myocardial fibrosis, and improved cardiac function post-MI. In vitro, overexpression of Ubc9 decreased cardiomyocyte apoptosis, whereas silence of Ubc9 showed the opposite results during OGD. We next found that Ubc9 significantly decreased the accumulation of autophagy marker p62/SQSTM, while the LC3 II level hardly changed. When in the presence of bafilomycin A1 (BAF), the Ubc9 adenovirus plus OGD group presented a higher level of LC3 II and GFP-LC3 puncta than the OGD group. Moreover, the Ubc9 adenovirus group displayed increased numbers of yellow plus red puncta and a rising ratio of red to yellow puncta on the mRFP-GFP-LC3 fluorescence assay, indicating that Ubc9 induces an acceleration of autophagic flux from activation to degradation. Mechanistically, Ubc9 upregulated SUMOylation of the core proteins Vps34 and Beclin1 in the class III phosphatidylinositol 3-kinase (PI3K-III) complexes, and bo...