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http://purl.uniprot.org/citations/29598867http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/29598867http://www.w3.org/2000/01/rdf-schema#comment"

Background

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.

Objectives

The purpose of this study was to detail how JNK promotes binge alcohol-evoked susceptibility to AF.

Methods

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.

Results

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.

Conclusions

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."xsd:string
http://purl.uniprot.org/citations/29598867http://purl.org/dc/terms/identifier"doi:10.1016/j.jacc.2018.01.060"xsd:string
http://purl.uniprot.org/citations/29598867http://purl.uniprot.org/core/author"Chen B."xsd:string
http://purl.uniprot.org/citations/29598867http://purl.uniprot.org/core/author"Gao X."xsd:string
http://purl.uniprot.org/citations/29598867http://purl.uniprot.org/core/author"Liang Q."xsd:string
http://purl.uniprot.org/citations/29598867http://purl.uniprot.org/core/author"Zhao W."xsd:string
http://purl.uniprot.org/citations/29598867http://purl.uniprot.org/core/author"Yan J."xsd:string
http://purl.uniprot.org/citations/29598867http://purl.uniprot.org/core/author"Huang F."xsd:string
http://purl.uniprot.org/citations/29598867http://purl.uniprot.org/core/author"Song L.S."xsd:string
http://purl.uniprot.org/citations/29598867http://purl.uniprot.org/core/author"Ai X."xsd:string
http://purl.uniprot.org/citations/29598867http://purl.uniprot.org/core/author"Fill M."xsd:string
http://purl.uniprot.org/citations/29598867http://purl.uniprot.org/core/author"Thomson J.K."xsd:string
http://purl.uniprot.org/citations/29598867http://purl.uniprot.org/core/date"2018"xsd:gYear
http://purl.uniprot.org/citations/29598867http://purl.uniprot.org/core/name"J Am Coll Cardiol"xsd:string
http://purl.uniprot.org/citations/29598867http://purl.uniprot.org/core/pages"1459-1470"xsd:string
http://purl.uniprot.org/citations/29598867http://purl.uniprot.org/core/title"Role of Stress Kinase JNK in Binge Alcohol-Evoked Atrial Arrhythmia."xsd:string
http://purl.uniprot.org/citations/29598867http://purl.uniprot.org/core/volume"71"xsd:string
http://purl.uniprot.org/citations/29598867http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/29598867
http://purl.uniprot.org/citations/29598867http://xmlns.com/foaf/0.1/primaryTopicOfhttps://pubmed.ncbi.nlm.nih.gov/29598867
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