| Title |
Role of Stress Kinase JNK in Binge Alcohol-Evoked Atrial Arrhythmia
|
|---|---|
| Published in |
JACC, April 2018
|
| DOI | 10.1016/j.jacc.2018.01.060 |
| Pubmed ID | |
| Authors |
Jiajie Yan, Justin K. Thomson, Weiwei Zhao, Xianlong Gao, Fei Huang, Biyi Chen, Qingrong Liang, Long-Sheng Song, Michael Fill, Xun Ai |
| Abstract |
Excessive binge alcohol drinking has acute cardiac arrhythmogenic effects, including promotion of atrial fibrillation (AF), which underlies "Holiday Heart Syndrome." The mechanism that couples binge alcohol abuse with AF susceptibility remains unclear. We previously reported stress-activated c-Jun N-terminal kinase (JNK) signaling contributes to AF development. This is interesting because JNK is implicated in alcohol-caused organ malfunction beyond the heart. The purpose of this study was to detail how JNK promotes binge alcohol-evoked susceptibility to AF. The authors found binge alcohol-exposure leads to activated JNK, specifically JNK2. Furthermore, binge alcohol induces AF (24- vs. 1.8-Hz burst pacing-induced episodes per attempt per animal), higher incidence of diastolic intracellular Ca2+activity (Ca2+waves, sarcoplasmic reticulum [SR] Ca2+leakage), and membrane voltage (Vm) and systolic Ca2+release spatiotemporal heterogeneity (ΔtVm-Ca). These changes were completely eliminated by JNK inhibition both in vivo and in vitro. calmodulin kinase II (CaMKII) is a proarrhythmic molecule known to drive SR Ca2+mishandling. The authors report for the first time that binge alcohol activates JNK2, which subsequently phosphorylates the CaMKII protein, enhancing CaMKII-driven SR Ca2+mishandling. CaMKII inhibition eliminates binge alcohol-evoked arrhythmic activities. Our studies demonstrate that binge alcohol exposure activates JNK2 in atria, which then drives CaMKII activation, prompting aberrant Ca2+waves and, thus, enhanced susceptibility to atrial arrhythmia. Our results reveal a previously unrecognized form of alcohol-driven kinase-on-kinase proarrhythmic crosstalk. Atrial JNK2 function represents a potential novel therapeutic target to treat and/or prevent AF. |
X Demographics
The data shown below were collected from the profiles of 268 X users who shared this research output. Click here to find out more about how the information was compiled.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Spain | 50 | 19% |
| United States | 23 | 9% |
| Venezuela, Bolivarian Republic of | 11 | 4% |
| Mexico | 9 | 3% |
| Canada | 8 | 3% |
| United Kingdom | 6 | 2% |
| France | 6 | 2% |
| Chile | 5 | 2% |
| Colombia | 4 | 1% |
| Other | 39 | 15% |
| Unknown | 107 | 40% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Members of the public | 201 | 75% |
| Practitioners (doctors, other healthcare professionals) | 37 | 14% |
| Scientists | 23 | 9% |
| Science communicators (journalists, bloggers, editors) | 7 | 3% |
Mendeley readers
The data shown below were compiled from readership statistics for 46 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 46 | 100% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Student > Ph. D. Student | 9 | 20% |
| Student > Master | 5 | 11% |
| Student > Doctoral Student | 4 | 9% |
| Researcher | 4 | 9% |
| Other | 3 | 7% |
| Other | 7 | 15% |
| Unknown | 14 | 30% |
| Readers by discipline | Count | As % |
|---|---|---|
| Medicine and Dentistry | 16 | 35% |
| Biochemistry, Genetics and Molecular Biology | 3 | 7% |
| Engineering | 3 | 7% |
| Immunology and Microbiology | 2 | 4% |
| Psychology | 1 | 2% |
| Other | 1 | 2% |
| Unknown | 20 | 43% |
Attention Score in Context
This research output has an Altmetric Attention Score of 171. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 22 July 2023.
All research outputs
#241,683
of 25,766,791 outputs
Outputs from JACC
#550
of 16,939 outputs
Outputs of similar age
#5,476
of 344,906 outputs
Outputs of similar age from JACC
#18
of 408 outputs
Altmetric has tracked 25,766,791 research outputs across all sources so far. Compared to these this one has done particularly well and is in the 99th percentile: it's in the top 5% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 16,939 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 30.1. This one has done particularly well, scoring higher than 96% of its peers.
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