Selective inhibition of histamine-evoked Ca2+ signals by compartmentalized cAMP in human bronchial airway smooth muscle cells

Dale, Philippa; Head, Victoria; Dowling, Mark R.; Taylor, Colin W.

doi:10.1016/j.ceca.2017.12.002

Cited by 18 publications

(11 citation statements)

References 52 publications

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“…It is therefore possible that the two events occur simultaneously. Interestingly, Dale et al (47) are able to observe an effect on histamine but not on other Ca 2ϩ -mobilizing agents, suggesting a certain degree of specificity. Preliminary data from our lab also shows that the mito-hTAS2R46 regulates mitochondrial calcium buffering chondrial uptake increase is not evident when carbachol or bradykinin are used to induce Ca 2ϩ mobilization.…”

Section: Htas2r46 Regulates Mitochondrial Calcium Bufferingmentioning

confidence: 95%

“…Recently, Dale et al (47) have shown that in human bronchial airway smooth muscle cells, histamine-induced cytosolic Ca 2ϩ rises may be blunted by isoproterenol and proposed a model by which compartmentalized cAMP rises negatively feedback via PKA to the histamine receptor. In our study, we were unable to determine the absolute level of Ca 2ϩ released and therefore cannot rule out that IP 3 formation from histamine activation is reduced upon TAS2R46 activation.…”

Section: Htas2r46 Regulates Mitochondrial Calcium Bufferingmentioning

confidence: 99%

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Absinthin, an agonist of the bitter taste receptor hTAS2R46, uncovers an ER-to-mitochondria Ca2+–shuttling event

Talmon

Rossi

Lim

et al. 2019

Journal of Biological Chemistry

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Type 2 taste receptors (TAS2R) are G protein-coupled receptors first described in the gustatory system, but have also been shown to have extraoral localizations, including airway smooth muscle (ASM) cells, in which TAS2R have been reported to induce relaxation. TAS2R46 is an unexplored subtype that responds to its highly specific agonist absinthin. Here, we first demonstrate that, unlike other bitter-taste receptor agonists, absinthin alone (1 M) in ASM cells does not induce Ca 2؉ signals but reduces histamine-induced cytosolic Ca 2؉ increases. To investigate this mechanism, we introduced into ASM cells aequorin-based Ca 2؉ probes targeted to the cytosol, subplasma membrane domain, or the mitochondrial matrix. We show that absinthin reduces cytosolic histamine-induced Ca 2؉ rises and simultaneously increases Ca 2؉ influx into mitochondria. We found that this effect is inhibited by the potent human TAS2R46 (hTAS2R46) antagonist 3␤-hydroxydihydrocostunolide and is no longer evident in hTAS2R46-silenced ASM cells, indicating that it is hTAS2R46-dependent. Furthermore, these changes were sensitive to the mitochondrial uncoupler carbonyl cyanide p-(trifluoromethoxy)phenyl-hydrazone (FCCP); the mitochondrial calcium uniporter inhibitor KB-R7943 (carbamimidothioic acid); the cytoskeletal disrupter latrunculin; and an inhibitor of the exchange protein directly activated by cAMP (EPAC), ESI-09. Similarly, the ␤2 agonist salbutamol also could induce Ca 2؉ shuttling from cytoplasm to mitochondria, suggesting that this new mechanism might be generalizable. Moreover, forskolin and an EPAC activator mimicked this effect in HeLa cells. Our findings support the hypothesis that plasma membrane receptors can positively regulate mitochondrial Ca 2؉ uptake, adding a further facet to the ability of cells to encode complex Ca 2؉ signals. This work was supported by Regione Piemonte Grant on Autoimmunity and Allergic Diseases D.D. n.195 18/07/2014 (to L. G. F.). The authors declare that they have no conflicts of interest with the contents of this article. This article contains supporting Experimental procedures and Figs. S1-S6.

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Section: Htas2r46 Regulates Mitochondrial Calcium Bufferingmentioning

confidence: 95%

Section: Htas2r46 Regulates Mitochondrial Calcium Bufferingmentioning

confidence: 99%

Absinthin, an agonist of the bitter taste receptor hTAS2R46, uncovers an ER-to-mitochondria Ca2+–shuttling event

Talmon

Rossi

Lim

et al. 2019

Journal of Biological Chemistry

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“…The change in intracellular Ca2+ concentration was represented by the change of fluorescence intensity. The ratio of fluorescence intensity (F/F0) was used to compare intracellular Ca2+ concentration under different treatments (F: the average fluorescence intensity under different treatments, F0: the initial fluorescence intensity) (Dale et al, 2018;Zhu et al, 2018).…”

Section: Measurements Of [Ca2+]i and Store-operated Calcium Entrymentioning

confidence: 99%

Role of TG2-Mediated SERCA2 Serotonylation on Hypoxic Pulmonary Vein Remodeling

et al. 2020

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Sarco-endoplasmic reticulum Ca2+ ATPase (SERCA) pumps take up Ca2+ from the cytoplasm to maintain the balance of intracellular Ca2+. A decline in expression or activity of SERCA results in persistent store-operated calcium entry (SOCE). In cardiomyocytes as well as vascular smooth muscle cells (SMCs), SERCA2 acts as an important regulator of calcium cycling. The purpose of this study is to identify and better understand the role of transglutaminases2 (TG2) as a key factor involved in SERCA2 serotonination (s-SERCA2) and to elucidate the underlying mechanism of action. Human pulmonary venous smooth muscle cell in normal pulmonary lobe were isolated and cultured in vitro. Establishment of hypoxic pulmonary hypertension model in wild type and TG2 knockout mice. SERCA2 serotonylation was analyzed by co-(immunoprecipitation) IP when the TG2 gene silenced or overexpressed under normoxia and hypoxia in vivo and in vitro. Intracellular calcium ion was measured by using Fluo-4AM probe under normoxia and hypoxia. Real-time (RT)-PCR and Western blot analyzed expression of TG2, TRPC1, and TRPC6 under normoxia and hypoxia. Bioactivity of cells were analyzed by using Cell Counting Kit (CCK)-8, flow cytometry, wound healing, RT-PCR, and Western blot under PST-2744 and cyclopiazonic acid. We confirmed that 1) hypoxia enhanced the expression and activity of TG2, and 2) hypoxia increased the basal intracellular Ca2+ concentration ([Ca2+]i) and SOCE through activating TRPC6 on human pulmonary vein smooth muscle cells (hPVSMC). Then, we investigated the effects of overexpression and downregulation of the TG2 gene on the activity of SERCA2, s-SERCA2, basal [Ca2+]i, and SOCE under normoxia and hypoxia in vitro, and investigated the activity of SERCA2 and s-SERCA2 in vivo, respectively. We confirmed that SERCA2 serotonylation inhibited the activity of SERCA2 and increased the Ca2+ influx, and that hypoxia induced TG2-mediated SERCA2 serotonylation both in vivo and in vitro. Furthermore, we investigated the effect of TG2 activity on the biological behavior of hPVSMC by using an inhibitor and agonist of SERCA2, respectively. Finally, we confirmed that chronic hypoxia cannot increase vessel wall thickness, the right ventricular systolic pressure (RVSP), and right ventricular hypertrophy index (RVHI) of vascular smooth muscle-specific Tgm2−/− mice. These results indicated that hypoxia promoted TG2-mediated SERCA2 serotonylation, thereby leading to inhibition of SERCA2 activity, which further increased the calcium influx through the TRPC6

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“…Activation of adenylate cyclase (AC) and subsequent increase in the production of cyclic adenosine monophosphate (cAMP) involves the interaction of β‐adrenergic receptor with guanosine triphosphate (GTP) binding proteins such as Gs and Gi, which allows functional coupling of the receptor. Formation of cAMP by AC is important in a variety of physiological and pathological events (Houslay, 1991; Chakraborti et al, 2000; Dale et al, 2018).…”

Section: Introductionmentioning

confidence: 99%

Role of PKCζ‐NADPH oxidase signaling axis in PKCα‐mediated Giα2 phosphorylation for inhibition of adenylate cyclase activity by angiotensin II in pulmonary artery smooth muscle cells

Chowdhury

Sarkar

Pramanik

et al. 2020

Cell Biology International

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We sought to determine the mechanism by which angiotensin II (AngII) inhibits isoproterenol induced increase in adenylate cyclase (AC) activity and cyclic adenosine monophosphate (cAMP) production in bovine pulmonary artery smooth muscle cells (BPASMCs). Treatment with AngII stimulates protein kinase C-ζ (PKC-ζ), nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, and PKC-α activities, and also inhibits isoproterenol induced increase in AC activity and cAMP production in the cells. Pertussis toxin pretreatment eliminates AngII caused inhibition of isoproterenol induced increase in AC activity without a discernible change in PKC-ζ, NADPH oxidase, and PKC-α activities. Treatment of the cells with AngII increases α2 isoform of Gi (Giα2) phosphorylation; while pretreatment with chemical and genetic inhibitors of PKC-ζ and NADPH oxidase attenuate AngII induced increase in PKC-α activity and Giα2 phosphorylation, and also reverse AngII caused inhibition of isoproterenol induced increase in AC activity. Pretreatment of the cells with chemical and genetic inhibitors of PKC-α attenuate AngII induced increase in Giα2 phosphorylation and inhibits isoproterenol induced increase in AC activity without a discernible change in PKC-ζ and NADPH oxidase activities. Overall, PKCζ-NADPH oxidase-PKCα signaling axis plays a crucial role in Giα2 phosphorylation resulting in AngII-mediated inhibition of isoproterenol induced increase in AC activity in BPASMCs.

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Selective inhibition of histamine-evoked Ca2+ signals by compartmentalized cAMP in human bronchial airway smooth muscle cells

Abstract: Graphical abstract

Cited by 18 publications

References 52 publications

Absinthin, an agonist of the bitter taste receptor hTAS2R46, uncovers an ER-to-mitochondria Ca2+–shuttling event

Absinthin, an agonist of the bitter taste receptor hTAS2R46, uncovers an ER-to-mitochondria Ca2+–shuttling event

Role of TG2-Mediated SERCA2 Serotonylation on Hypoxic Pulmonary Vein Remodeling

Role of PKCζ‐NADPH oxidase signaling axis in PKCα‐mediated Giα2 phosphorylation for inhibition of adenylate cyclase activity by angiotensin II in pulmonary artery smooth muscle cells

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