Restraint Stress Induces Connexin-43 Translocation via &amp;alpha;-Adrenoceptors in Rat Heart

Unuma, Kana; Shintani-Ishida, Kaori; Yahagi, Naoki; Tsushima, Kensuke; Shimosawa, Tatsuo; Umemura, Takashi; Yoshida, Kenichi

doi:10.1253/circj.cj-10-0529

Cited by 6 publications

(6 citation statements)

References 41 publications

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“…Previously, we demonstrated that IMO induced arrhythmic death when coupled with the GJ inhibition that frequently results from heart diseases. 9,10) This study has provided additional support for the hypothesis on the role of cardiogenic death in restraint.…”

Section: Discussionsupporting

confidence: 61%

“…8) We also showed that whereas IMO induced enhanced gap-junction (GJ) coupling through α-AR, it triggered lethal ventricular arrhythmias when GJ was inhibited. 9,10) Stress (takotsubo) cardiomyopathy is typically induced by psychological stress in postmenopausal women, and is characterized by apical myocardial akinesis and preserved basal movement, which is reflected by a takotsubo (Japanese octopus trap)-like ventriculogram.…”

Section: -3)mentioning

confidence: 99%

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Immobilization Stress With α2-Adrenergic Stimulation Induces Regional and Transient Reduction of Cardiac Contraction Through Gi Coupling in Rats

et al. 2015

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SummaryStress cardiomyopathy is characterized by transient apical hypokinesia related to catecholamine overflow. Recently, excessive epinephrine administration was shown to recapitulate stress cardiomyopathy through β 2 -adrenoceptor (AR)-inhibitory G protein (Gi) coupling in rats. We aimed to study whether α 2 -AR and Gi affect cardiac contraction in rats in which emotional stress was evoked using immobilization (IMO). Echocardiography results showed that when male rats were exposed to IMO for 30 minutes and then injected with the α 2 -AR agonist xylazine (Xy), ejection fraction and the movement of the anterior wall (AW) were suppressed, maximally at 5 minutes post-injection, whereas posterior wall (PW) movement was preserved. At the same time points, the phosphorylation of Ser282 in myosin-binding protein-C (MyBP-C-Ser282) was higher in the PW than in the AW. Pretreatment with the Gi inhibitor pertussis toxin (PTX) reversed the low contractility and MyBP-C-Ser282 phosphorylation in the AW, but induced lethal heart failure in 3 out of 11 rats. Moreover, at 5 minutes after Xy injection following 30 minutes of IMO, serum epinephrine levels were increased. Thus, in rats exposed to psychological stress, α 2 -AR stimulation triggered transient hypo-contractility and MyBP-C-Ser282 hypo-phosphorylation in the AW, in association with an epinephrine surge. PTX treatment reversed the AW hypo-contractility and MyBP-C hypo-phosphorylation, but induced acute heart failure. These findings suggest α 2 -AR/Gi-dependent signaling attenuates MyBP-C phosphorylation and contractility in the AW through an epinephrine surge in rats subjected to IMO and α 2 -AR stimulation. This model can recapitulate stress cardiomyopathy and thereby deepen our understanding of regional cardiac hypo-contractility and prosurvival mechanisms. Studies on psychological stress conducted using immobilization (IMO) in rats demonstrated the activation of the hypothalamo-pituitary-adrenocortical and sympatho-adrenomedullary axes. [4][5][6] This model served to establish the fight-andflight doctrine of Hans Selye 7) and has contributed to studies on cardiovascular responses to emotional stress. We reported that IMO induces the expression of cardiac immediate-early genes through α-and β-adrenoceptors (ARs) in rats.8) We also showed that whereas IMO induced enhanced gap-junction (GJ) coupling through α-AR, it triggered lethal ventricular arrhythmias when GJ was inhibited. 9,10)

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Section: Discussionsupporting

confidence: 61%

Section: -3)mentioning

confidence: 99%

Immobilization Stress With α2-Adrenergic Stimulation Induces Regional and Transient Reduction of Cardiac Contraction Through Gi Coupling in Rats

et al. 2015

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“…Because DCM mice are highly sensitive to anesthesia including inhalation and intravenous anesthetics, these data were obtained from conscious mice. Four of eight LO mice died before measurements were obtained, which was probably related to restraint [21]. A significantly higher left ventricular end-diastolic dimension (LVDd) and significantly lower ejection fraction (EF) were recorded in the LO mice that survived restraint than in the HI mice (Fig.…”

Section: Resultsmentioning

confidence: 97%

Usefulness of Running Wheel for Detection of Congestive Heart Failure in Dilated Cardiomyopathy Mouse Model

et al. 2013

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BackgroundInherited dilated cardiomyopathy (DCM) is a progressive disease that often results in death from congestive heart failure (CHF) or sudden cardiac death (SCD). Mouse models with human DCM mutation are useful to investigate the developmental mechanisms of CHF and SCD, but knowledge of the severity of CHF in live mice is necessary. We aimed to diagnose CHF in live DCM model mice by measuring voluntary exercise using a running wheel and to determine causes of death in these mice.Methodology/Principal FindingsA knock-in mouse with a mutation in cardiac troponin T (ΔK210) (DCM mouse), which results in frequent death with a t1/2 of 70 to 90 days, was used as a DCM model. Until 2 months of age, average wheel-running activity was similar between wild-type and DCM mice (approximately 7 km/day). At approximately 3 months, some DCM mice demonstrated low running activity (LO: <1 km/day) while others maintained high running activity (HI: >5 km/day). In the LO group, the lung weight/body weight ratio was much higher than that in the other groups, and the lungs were infiltrated with hemosiderin-loaded alveolar macrophages. Furthermore, echocardiography showed more severe ventricular dilation and a lower ejection fraction, whereas Electrocardiography (ECG) revealed QRS widening. There were two patterns in the time courses of running activity before death in DCM mice: deaths with maintained activity and deaths with decreased activity.Conclusions/SignificanceOur results indicate that DCM mice with low running activity developed severe CHF and that running wheels are useful for detection of CHF in mouse models. We found that approximately half of ΔK210 DCM mice die suddenly before onset of CHF, whereas others develop CHF, deteriorate within 10 to 20 days, and die.

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“…In the past 10 years, we have processed thousands of Affymetrix gene expression arrays. Recently, evidence has shown that microarray is reliable because of the newly development of technology and analytical tool [13, 14]. We carefully checked the quality of the microarray data before we utilized them.…”

Section: Resultsmentioning

confidence: 99%

Genome Wide Analysis of Sex Difference in Gene Expression Profiles of Bone Formations UsingsfxMice and BXD RI Strains

Huang

Zhu

Wang

et al. 2014

The Scientific World Journal

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The objective of this study is to identify sex differentially expressed genes in bone using a mouse model of spontaneous fracture, sfx, which lacks the gene for L-gulonolactone oxidase (Gulo), a key enzyme in the ascorbic acid (AA) synthesis pathway. We first identified the genes that are differentially expressed in the femur between female and male in sfx mice. We then analyzed the potential gene network among those differentially expressed genes with whole genome expression profiles generated using spleens of female and male mice of a total of 67 BXD (C57BL/6J X DBA/2J) recombinant inbred (RI) and other strains. Our result indicated that there was a sex difference in the whole genome profiles in sfx mice as measured by the proportion of up- and downregulated genes. Several genes in the pathway of bone development are differentially expressed between the male and female of sfx mice. Comparison of gene network of up- and downregulated bone relevant genes also suggests a sex difference.

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Restraint Stress Induces Connexin-43 Translocation via α-Adrenoceptors in Rat Heart

Cited by 6 publications

References 41 publications

Immobilization Stress With <i>α</i><sub>2</sub>-Adrenergic Stimulation Induces Regional and Transient Reduction of Cardiac Contraction Through Gi Coupling in Rats

Immobilization Stress With <i>α</i><sub>2</sub>-Adrenergic Stimulation Induces Regional and Transient Reduction of Cardiac Contraction Through Gi Coupling in Rats

Usefulness of Running Wheel for Detection of Congestive Heart Failure in Dilated Cardiomyopathy Mouse Model

Genome Wide Analysis of Sex Difference in Gene Expression Profiles of Bone Formations UsingsfxMice and BXD RI Strains

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