| Literature DB >> 27108530 |
Yuuki Shimizu1, Jonathan P Lambert1, Chad K Nicholson1, Joshua J Kim1, David W Wolfson2, Hee Cheol Cho2, Ahsan Husain3, Nawazish Naqvi3, Li-Shen Chin4, Lian Li4, John W Calvert5.
Abstract
Recent data indicates that DJ-1 plays a role in the cellular response to stress. Here, we aimed to examine the underlying molecular mechanisms mediating the actions of DJ-1 in the heart following myocardial ischemia-reperfusion (I/R) injury. In response to I/R injury, DJ-1 KO mice displayed increased areas of infarction and worsened left ventricular function when compared to WT mice, confirming a protective role for DJ-1 in the heart. In an effort to evaluate the potential mechanism(s) responsible for the increased injury in DJ-1 KO mice, we focused on SUMOylation, a post-translational modification process that regulates various aspects of protein function. DJ-1 KO hearts after I/R injury were found to display enhanced accumulation of SUMO-1 modified proteins and reduced SUMO-2/3 modified proteins. Further analysis, revealed that the protein expression of the de-SUMOylation enzyme SENP1 was reduced, whereas the expression of SENP5 was enhanced in DJ-1 KO hearts after I/R injury. Finally, DJ-1 KO hearts were found to display enhanced SUMO-1 modification of dynamin-related protein 1, excessive mitochondrial fission, and dysfunctional mitochondria. Our data demonstrates that the activation of DJ-1 in response to myocardial I/R injury protects the heart by regulating the SUMOylation status of Drp1 and attenuating excessive mitochondrial fission.Entities:
Keywords: DJ-1; Mitochondrial fission; Myocardial ischemia; SUMOylation
Mesh：
Substances：
Year: 2016 PMID： 27108530 PMCID： PMC5002379 DOI： 10.1016/j.yjmcc.2016.04.008
Source DB: PubMed Journal: J Mol Cell Cardiol ISSN： 0022-2828 Impact factor: 5.000