Role of Stress Kinase JNK in Binge Alcohol-Evoked Atrial Arrhythmia

Yan, Jiajie; Thomson, Justin K.; Zhao, Weiwei; Gao, Xianlong; Huang, Fei; Chen, Biyi; Liang, Qing-Rong; Song, Long‐Sheng; Fill, Michael; Ai, Xun

doi:10.1016/j.jacc.2018.01.060

Cited by 66 publications

(84 citation statements)

References 39 publications

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“…It was shown that GC stimulation results in increased ER stress, measured as reduced methylation of FK binding protein 51 (FKBP51) [60]. Importantly, increased ER stress has been linked to increased Ca spark activity and atrial fibrillation via increased phosphorylation and activation of CaMKIIδ in human, rabbit and mouse atrial tissue [62,63]. Moreover, direct stimulation of SOCE by high doses of 2-aminoethoxydiphenyl borate (2-APB; 20 μM) has been shown to induce arrhythmias and spontaneous contractions in an Orai-dependent fashion in rat atrial and ventricular myocytes [64].…”

Section: Discussionmentioning

confidence: 99%

Glucocorticoid stimulation increases cardiac contractility by SGK1-dependent SOCE-activation in rat cardiac myocytes

et al. 2019

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AimsGlucocorticoid (GC) stimulation has been shown to increase cardiac contractility by elevated intracellular [Ca] but the sources for Ca entry are unclear. This study aims to determine the role of store-operated Ca entry (SOCE) for GC-mediated inotropy.Methods and resultsDexamethasone (Dex) pretreatment significantly increased cardiac contractile force ex vivo in Langendorff-perfused Sprague-Dawley rat hearts (2 mg/kg BW i.p. Dex 24 h prior to experiment). Moreover, Ca transient amplitude as well as fractional shortening were significantly enhanced in Fura-2-loaded isolated rat ventricular myocytes exposed to Dex (1 mg/mL Dex, 24 h). Interestingly, these Dex-dependent effects could be abolished in the presence of SOCE-inhibitors SKF-96356 (SKF, 2 μM) and BTP2 (5 μM). Ca transient kinetics (time to peak, decay time) were not affected by SOCE stimulation. Direct SOCE measurements revealed a negligible magnitude in untreated myocytes but a dramatic increase in SOCE upon Dex-pretreatment. Importantly, the Dex-dependent stimulation of SOCE could be blocked by inhibition of serum and glucocorticoid-regulated kinase 1 (SGK1) using EMD638683 (EMD, 50 μM). Dex preincubation also resulted in increased mRNA expression of proteins involved in SOCE (stromal interaction molecule 2, STIM2, and transient receptor potential cation channels 3/6, TRPC 3/6), which were also prevented in the presence of EMD.ConclusionShort-term GC-stimulation with Dex improves cardiac contractility by a SOCE-dependent mechanism, which appears to involve increased SGK1-dependent expression of the SOCE-related proteins. Since Ca transient kinetics were unaffected, SOCE appears to influence Ca cycling more by an integrated response across multiple cardiac cycles but not on a beat-to-beat basis.

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Section: Discussionmentioning

confidence: 99%

Glucocorticoid stimulation increases cardiac contractility by SGK1-dependent SOCE-activation in rat cardiac myocytes

et al. 2019

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“…Furthermore, there are other promising approaches in terms of research of the JNK role in alcohol drinking. Yang et al showed an interesting insight into the development of alcohol-induced liver steatosis and the involvement of cytochrome P4502E1 and JNK activation [ 45 ], while Yan et al underlined the possible role of JNK in the binge drinking-related progression of atrial arrhythmia in the holiday heart syndrome [ 46 ]. Further research on the JNK role in chronic inflammatory diseases should be considered.…”

Section: Discussionmentioning

confidence: 99%

Anti-inflammatory Effects of Alcohol Are Associated with JNK-STAT3 Downregulation in an In Vitro Inflammation Model in HepG2 Cells

et al. 2021

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Background. In several preclinical and in vitro models of acute inflammation, alcohol (ethanol, EtOH) has been described as an immunomodulatory agent. Similarly, in different pathologies, clinical observations have confirmed either pro- or anti-inflammatory effects of EtOH. The liver plays an important role in immunity and alcohol metabolism; therefore, we analysed dose- and time-dependent effects of EtOH on the inflammatory response of human liver cells in an in vitro model of acute inflammation. Methods. HepG2 cells were stimulated with IL-1β and subsequently exposed to EtOH in a low or high dose (85 mM, LoD or 170 mM, HiD) for 1 h (acute exposure) or 72 h (prolonged exposure). IL-6 and TNF-α release was determined by ELISA. Cell viability, adhesion of isolated neutrophils to HepG2 monolayers, their ICAM-1 expression, and the activation of stress-induced protein kinase/c-Jun N-terminal kinase (SAPK/JNK) or signal transducer and activator of transcription 3 (STAT3) were analysed. Results. In this experimental design, EtOH did not markedly change the cell viability. Acute and prolonged exposure to EtOH significantly reduced dose-independent IL-1β-induced IL-6 and TNF-α release, as well as adhesion capacity to pretreated HepG2 cells. Acute exposure to EtOH significantly decreased the percentage of ICAM-1-expressing cells. IL-1β stimulation notably increased the activation of SAPK/JNK. However, low-dose EtOH exposure reduced this activation considerably, in contradiction to high-dose EtOH exposure. Acute exposure to LoD EtOH significantly diminished the IL-1β-induced STAT3 activation, whereas an acute exposure of cells to either HiD EtOH or in a prolonged setting showed no effects on STAT3 activation. Conclusion. EtOH exerts anti-inflammatory potential in this in vitro model of hepatic inflammation. These effects are associated with the reduced activation of JNK/STAT3 by EtOH, particularly in the condition of acute exposure to low-dose EtOH.

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“…Exposure to ethanol or acetaldehyde (a byproduct of ethanol) can lead to abnormal concentrations of intracellular Ca 2+ [26]. Therefore, alcohol exposure activates stress kinases in atrial myocytes thereby prompting aberrant Ca 2+ waves which results in increased susceptibility to atrial arrhythmias [27].…”

Section: Discussionmentioning

confidence: 99%

A Dose-Response Meta-Analysis on the Association Between Alcohol Consumption and Incidence of Atrial Fibrillation

Zhang

Yang

et al. 2020

Preprint

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Background: Atrial fibrillation (AF) is one of the most common arrhythmias in clinical practice. Alcohol consumption has been linked to the occurrence of AF.Methods: A comprehensive search of electronic databases (PubMed, Cochrane Library, OVID, Google scholar, and Web of Science) was performed. The search yielded a total of 1177 articles, and 12 cohort studies from the total were included in the meta-analysis. The effects of different doses of alcohol consumption on the risk of AF in men and women were compared using hierarchical analysis. Dose-response curves of alcohol consumption and risk of AF were plotted for the two groups according to sex.Results: The risk of AF increased with increased alcohol consumption in both men and women. In the male population, light-moderate alcohol consumption did not increase the risk of AF (HR: 1.07, 95%CI: 0.92-1.23, P=0.38), while heavy alcohol consumption significantly increased the risk of AF (HR: 1.38, 95%CI: 1.23-1.54, P<0.01). In the female population, the risk of AF was not significantly increased by either light-moderate or heavy alcohol consumption (light- moderate drink: HR: 1.00, 95%CI: 0.92-1.10, P=0.95; heavy drink: HR: 1.05, 95%CI: 0.90-1.23, P=0.55).Conclusions: In women, the risk of AF was not associated with any degree of alcohol consumption while high levels of alcohol consumption significantly increased the risk of AF in men.

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Role of Stress Kinase JNK in Binge Alcohol-Evoked Atrial Arrhythmia

Cited by 66 publications

References 39 publications

Glucocorticoid stimulation increases cardiac contractility by SGK1-dependent SOCE-activation in rat cardiac myocytes

Glucocorticoid stimulation increases cardiac contractility by SGK1-dependent SOCE-activation in rat cardiac myocytes

Anti-inflammatory Effects of Alcohol Are Associated with JNK-STAT3 Downregulation in an In Vitro Inflammation Model in HepG2 Cells

A Dose-Response Meta-Analysis on the Association Between Alcohol Consumption and Incidence of Atrial Fibrillation

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