Mesubi, Olurotimi O. and Rokita, Adam G. and Abrol, Neha and Wu, Yuejin and Chen, Biyi and Wang, Qinchuan and Granger, Jonathan M. and Tucker-Bartley, Anthony and Luczak, Elizabeth D. and Murphy, Kevin R. and Umapathi, Priya and Banerjee, Partha S. and Boronina, Tatiana N. and Cole, Robert N. and Maier, Lars S. and Wehrens, Xander H. and Pomerantz, Joel L. and Song, Long-Sheng and Ahima, Rexford S. and Hart, Gerald W. and Zachara, Natasha E. and Anderson, Mark E. (2021) Oxidized CaMKII and O-GlcNAcylation cause increased atrial fibrillation in diabetic mice by distinct mechanisms. JOURNAL OF CLINICAL INVESTIGATION, 131 (2): e95747. ISSN 0021-9738, 1558-8238
Full text not available from this repository. (Request a copy)Abstract
Diabetes mellitus (DM) and atrial fibrillation (AF) are major unsolved public health problems, and diabetes is an independent risk factor for AF. However, the mechanism(s) underlying this clinical association is unknown. ROS and protein O-GlcNAcylation (OGN) are increased in diabetic hearts, and calmodulin kinase II (CaMKII) is a proarrhythmic signal that may be activated by ROS (oxidized CaMKII, ox-CaMKII) and OGN (OGN-CaMKII). We induced type 1 (T1D) and type 2 DM (T2D) in a portfolio of genetic mouse models capable of dissecting the role of ROS and OGN at CaMKII and global OGN in diabetic AF. Here, we showed that T1D and T2D significantly increased AF, and this increase required CaMKII and OGN. T1D and T2D both required ox-CaMKII to increase AF; however, we did not detect OGN-CaMKII or a role for OGN-CaMKII in diabetic AF. Collectively, our data affirm CaMKII as a critical proarrhythmic signal in diabetic AF and suggest ROS primarily promotes AF by ox-CaMKII, while OGN promotes AF by a CaMKII-independent mechanism(s). These results provide insights into the mechanisms for increased AF in DM and suggest potential benefits for future CaMKII and OGN targeted therapies.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | PROTEIN-KINASE-II; BETA-N-ACETYLGLUCOSAMINE; INDEPENDENT ACTIVATION; INSULIN-RESISTANCE; HEART-FAILURE; GLOBAL BURDEN; RISK-FACTORS; CELL-DEATH; CA2+ LEAK; PREVALENCE; |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Innere Medizin II |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 27 Sep 2022 09:26 |
| Last Modified: | 27 Sep 2022 09:26 |
| URI: | https://pred.uni-regensburg.de/id/eprint/48050 |
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