Interleukin-1β Reduces L-type Ca2+ Current through Protein Kinase Cϵ Activation in Mouse Heart

Khoury, Nabil; Mathieu, Sophie; Fiset, Céline

doi:10.1074/jbc.m114.549642

Cited by 50 publications

(31 citation statements)

References 53 publications

(82 reference statements)

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“…Similar results have been reported in rat portal vein myocytes (50). In contrast, a PKCinduced I Ca,L decrease has been described in the heart (58,59) and cerebral artery smooth muscle cells (60). Biphasic effects of PKC and no effect of PKC activation on L-type Ca 2ϩ channels have also been reported (61,62).…”

Section: Discussionsupporting

confidence: 66%

Urotensin-II Receptor Stimulation of Cardiac L-type Ca2+ Channels Requires the βγ Subunits of Gi/o-protein and Phosphatidylinositol 3-Kinase-dependent Protein Kinase C β1 Isoform

Zhang

Ying

Jiang

et al. 2015

Journal of Biological Chemistry

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Background: Regulation of L-type Ca 2ϩ channels has important roles in determining the electrical properties of cardiomyocytes. Results: U-II potentiates I Ca,L via U-IIR that couples to the PI3K-dependent PKC␤ 1 isoform. Conclusion: U-IIR stimulation of I Ca,L contributes to the increase in the amplitude of sarcomere shortening. Significance: Regulation of I Ca,L by U-IIR plays important roles in cardiovascular actions including cardiac positive inotropic effects and increasing cardiac output.

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Section: Discussionsupporting

confidence: 66%

Urotensin-II Receptor Stimulation of Cardiac L-type Ca2+ Channels Requires the βγ Subunits of Gi/o-protein and Phosphatidylinositol 3-Kinase-dependent Protein Kinase C β1 Isoform

Zhang

Ying

Jiang

et al. 2015

Journal of Biological Chemistry

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“…Moreover, IL-1β depresses cardiac contractility by reducing L-type Ca 2+ currents in neonatal and adult ventricular cardiomyocytes [25], and by inhibiting their β-adrenergic response [26]. We show here that inhibition of hematopoietic RANKL reduces transcription of the pro-inflammatory cytokine IL-1β in the myocardium, and more specifically in scar-infiltrating inflammatory cells.…”

Section: Discussionmentioning

confidence: 92%

Selective inhibition of receptor activator of NF-κB ligand (RANKL) in hematopoietic cells improves outcome after experimental myocardial infarction

et al. 2018

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The RANK (receptor activator of nuclear factor κB)/RANKL (RANK ligand)/OPG (osteoprotegerin) axis is activated after myocardial infarction (MI), but its pathophysiological role is not well understood. Here, we investigated how global and cell compartment-selective inhibition of RANKL affects cardiac function and remodeling after MI in mice. Global RANKL inhibition was achieved by treatment of human RANKL knock-in (huRANKL-KI) mice with the monoclonal antibody AMG161. huRANKL-KI mice express a chimeric RANKL protein wherein part of the RANKL molecule is humanized. AMG161 inhibits human and chimeric but not murine RANKL. To dissect the pathophysiological role of RANKL derived from hematopoietic and mesenchymal cells, we selectively exchanged the hematopoietic cell compartment by lethal irradiation and across-genotype bone marrow transplantation between wild-type and huRANKL-KI mice, exploiting the specificity of AMG161. After permanent coronary artery ligation, mice were injected with AMG161 or an isotype control antibody over 4 weeks post-MI. MI increased RANKL expression mainly in cardiomyocytes and scar-infiltrating cells 4 weeks after MI. Only inhibition of RANKL derived from hematopoietic cellular sources, but not global or mesenchymal RANKL inhibition, improved post-infarct survival and cardiac function. Mechanistically, hematopoietic RANKL inhibition reduced expression of the pro-inflammatory cytokine IL-1ß in the cardiac cellular infiltrate. In conclusion, inhibition of RANKL derived from hematopoietic cellular sources is beneficial to maintain post-ischemic cardiac function by reduction of pro-inflammatory cytokine production.Key messages Experimental myocardial infarction (MI) augments cardiac RANKL expression in mice.RANKL expression is increased in cardiomyocytes and scar-infiltrating cells after MI.Global or mesenchymal cell RANKL inhibition has no influence on cardiac function after MI.Inhibition of RANKL derived from hematopoietic cells improves heart function post-MI.Hematopoietic RANKL inhibition reduces pro-inflammatory cytokines in scar-infiltrating cells. Electronic supplementary materialThe online version of this article (10.1007/s00109-018-1641-x) contains supplementary material, which is available to authorized users.

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“…14 In addition, TNF-a could also disrupt calcium homeostasis and increase the arrhythmogenicity of pulmonary vein cardiomyocytes, thereby leading to the onset of AF. 15 But research indicated that TNF-a had no effect on I Ca,L in neonatal mouse ventricular myocytes; 25 In mouse neurons, TNF-a significantly decreased voltage-gated Ca 2+ currents amplitude through selectively inhibiting N-type Ca 2+ channels, while L-type channels were unaffected. 26 Electrical remodelling is characteristic of AF, with shortening of the atrial effective refractory period and reduction of physiological rate adaptation.…”

Section: Discussionmentioning

confidence: 99%

Role of tumour necrosis factor‐a in the regulation of T‐type calcium channel current in HL‐1 cells

Rao

Xue

Wei

et al. 2016

Clin Exp Pharma Physio

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Increasing evidence indicates that inflammation contributes to the initiation and perpetuation of atrial fibrillation (AF). Although tumour necrosis factor (TNF)-α levels are increased in patients with AF, the role of TNF-α in the pathogenesis of AF remains unclear. Besides L-type Ca(2+) currents (IC a,L ), T-type Ca(2+) currents (IC a,T ) also plays an important role in the pathogenesis of AF. This study was designed to use the whole-cell voltage-clamp technique and biochemical assays to explore if TNF-α is involved in the pathogenesis of AF through regulating IC a,T in atrial myocytes. It was found that compared with sinus rhythm (SR) controls, T-type calcium channel (TCC) subunit mRNA levels were decreased, while TNF-α expression levels were increased, in human atrial tissue from patients with AF. In murine atrial myocyte HL-1 cells, after culturing for 24 h, 12.5, 25 and 50 ng/mL TNF-α significantly reduced the protein expression levels of the TCC α1G subunit in a concentration-dependent manner. The peak current was reduced by the application of 12.5 or 25 ng/mL TNF-α in a concentration-dependent manner (from -15.08 ± 1.11 pA/pF in controls to -11.89 ± 0.83 pA/pF and -8.54 ± 1.55 pA/pF in 12.5 or 25 ng/mL TNF-α group respectively). TNF-α application also inhibited voltage-dependent inactivation of IC a,T, shifted the inactivation curve to the left. These results suggest that TNF-α is involved in the pathogenesis of AF, probably via decreasing IC a,T current density in atrium-derived myocytes through impaired channel function and down-regulation of channel protein expression. This pathway thus represents a potential pathogenic mechanism in AF.

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Interleukin-1β Reduces L-type Ca2+ Current through Protein Kinase Cϵ Activation in Mouse Heart

Cited by 50 publications

References 53 publications

Urotensin-II Receptor Stimulation of Cardiac L-type Ca2+ Channels Requires the βγ Subunits of Gi/o-protein and Phosphatidylinositol 3-Kinase-dependent Protein Kinase C β1 Isoform

Urotensin-II Receptor Stimulation of Cardiac L-type Ca2+ Channels Requires the βγ Subunits of Gi/o-protein and Phosphatidylinositol 3-Kinase-dependent Protein Kinase C β1 Isoform

Selective inhibition of receptor activator of NF-κB ligand (RANKL) in hematopoietic cells improves outcome after experimental myocardial infarction

Role of tumour necrosis factor‐a in the regulation of T‐type calcium channel current in HL‐1 cells

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