期刊
JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY
卷 129, 期 -, 页码 69-78出版社
ELSEVIER SCI LTD
DOI: 10.1016/j.yjmcc.2019.02.009
关键词
GCN5L1; Ischemia reperfusion; ERK1/2; Reactive oxygen species; Ex vivo working heart
资金
- NIH [T32HL110849, K22HL116728, R56HL132917, R01HL132917]
- NATIONAL HEART, LUNG, AND BLOOD INSTITUTE [ZIAHL006047] Funding Source: NIH RePORTER
GCN5L1 regulates mitochondrial protein acetylation, cellular bioenergetics, reactive oxygen species (ROS) generation, and organelle positioning in a number of diverse cell types. However, the functional role of GCN5L1 in the heart is currently unknown. As many of the factors regulated by GCN5L1 play a major role in ischemia-reperfusion (I/R) injury, we sought to determine if GCN5L1 is an important nexus in the response to cardiac ischemic stress. Deletion of GCN5L1 in cardiomyocytes resulted in impaired myocardial post-ischemic function and increased infarct development in isolated work-performing hearts. GCN5L1 knockout hearts displayed hallmarks of ROS damage, and scavenging of ROS restored cardiac function and reduced infarct volume in vivo. GCN5L1 knockdown in cardiac-derived AC16 cells was associated with reduced activation of the pro-survival MAP kinase ERK1/2, which was also reversed by ROS scavenging, leading to restored cell viability. We therefore conclude that GCN5L1 activity provides an important protection against I/R induced, ROS-mediated damage in the ischemic heart.
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