Role of endothelin-1 receptors in the sarcolemma membrane and the nuclear membrane in the modulation of basal cytosolic and nuclear calcium levels in heart cells

Bkaily, Ghassan; Massaad, Danie; Choufani, Sanaa; Jacques, Danielle; D’Orléans-Juste, Pedro

doi:10.1042/cs103s141s

Cited by 26 publications

(22 citation statements)

References 17 publications

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“…All methods used for cell isolation and culture, confocal microscopy, ionic fluorescent probe loading, antibodies, solutions, and sources of all compounds as well as statistical analyses were the same as those reported before (Bkaily 1994;Bkaily et al 1996Bkaily et al , 1997Bkaily et al , 1998Bkaily et al , 1999Bkaily et al , 2000Bkaily et al , 2001Bkaily et al , 2002Bkaily et al , 2003Bkaily et al , 2004Bkaily et al , 2006Bkaily et al , 2009Bkaily et al , 2011Provost et al 2010).…”

Section: Methodsmentioning

confidence: 99%

Whole-cell and nuclear NADPH oxidases levels and distribution in human endocardial endothelial, vascular smooth muscle, and vascular endothelial cells

Ahmarani

Avedanian

Al-Khoury

et al. 2013

Can. J. Physiol. Pharmacol.

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The results of our study show that whole-cell and nuclear levels of NADPH oxidase-1 (NOX1) are similar in human vascular endothelial cells (hVECs) and smooth muscle cells (hVSMCs), but lower in human endocardial endothelial cells (hEECs). NOX2 levels were higher in hVECs and lower in hVSMCs. NOX3 levels were the same in hVECs and hVSMCs, but lower in hEECs. NOX4 levels were similar in all of the cell types. NOX4 levels were higher in hVECs than in hVSMCs. NOX5 was also present throughout the 3 cell types, including their nuclei, in the following order: hEECs > hVSMCs > hVECs. The level of basal reactive oxygen species (ROS) was highest in hVECs and lowest in hVSMCs. However, the Ca(2+) level was highest in hVSMCs and lowest in hVECs. These findings suggest that all types of NOXs exist in hEECs, hVECs, and hVSMCs, although their density and distribution are cell-type dependent. The density of the different NOXs correlated with the ROS level, but not with the Ca(2+) level. In conclusion, NOXs, including NOX3, exist in cardiovascular cells and their nuclei. The nucleus is a major source of ROS generation. The nuclear NOXs may contribute to ROS and Ca(2+) homeostasis, which may affect cell remodeling, including the formation of nuclear T-tubules in vascular diseases and aging.

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Section: Methodsmentioning

confidence: 99%

Whole-cell and nuclear NADPH oxidases levels and distribution in human endocardial endothelial, vascular smooth muscle, and vascular endothelial cells

Ahmarani

Avedanian

Al-Khoury

et al. 2013

Can. J. Physiol. Pharmacol.

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“…In another set of experiments, confocal microscopy was used to monitor spatiotemporal movements of nuclear Ca 2ϩ induced by SNP within a single nucleus using the calcium indicator dye fluo-4-AM as described (16,25). Intensity of fluorescence of the calcium-fluo-4 complex was converted into absolute calcium concentration as reported (26). Stimulated nuclei were recorded at a rate of 330 ms/scan (3 scans/s) for a total of 200 -250 frames.…”

Section: R/ Htc4 Cells (Not Shown)mentioning

confidence: 99%

Nitric Oxide Signaling via Nuclearized Endothelial Nitric-oxide Synthase Modulates Expression of the Immediate Early Genes iNOS and mPGES-1

Gobeil

Zhu

Brault

et al. 2006

Journal of Biological Chemistry

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Stimulation of freshly isolated rat hepatocytes with lysophosphatidic acid (LPA) resulted in LPA 1 receptor-mediated and nitricoxide-dependent up-regulation of the immediate early genes iNOS (inducible nitric-oxide synthase (NOS)) and mPGES-1 (microsomal prostaglandin E synthase-1). Because LPA is a ligand for both cell surface and intracellular receptor sites and a potent endothelial NOS (eNOS) activator, we hypothesized that NO derived from activated nuclearized eNOS might participate in gene regulation. Herein we show, by confocal microscopy performed on porcine cerebral endothelial cells expressing native LPA 1 -receptor and eNOS and on HTC4 rat hepatoma cells co-transfected with recombinant human LPA 1 -receptor and fused eNOS-GFP cDNA, a dynamic eNOS translocation from peripheral to nuclear regions upon stimulation with LPA. Nuclear localization of eNOS and its downstream effector, soluble guanylate cyclase, were demonstrated in situ in rat liver specimens by immunogold labeling using specific antibodies. Stimulation of this nuclear fraction with LPA and the NO donor sodium nitroprusside resulted, respectively, in increased production of nitrite (and eNOS phosphorylation) and cGMP; these separate responses were also correspondingly blocked by NOS inhibitor L-NAME and soluble guanylate cyclase inhibitor ODQ. In addition, sodium nitroprusside evoked a sequential increase in nuclear Ca 2؉ transients, activation of p42 MAPK, NF-B binding to DNA consensus sequence, and dependent iNOS RNA. This study describes a hitherto unrecognized molecular mechanism by which nuclear eNOS through ensuing NO modulates nuclear calcium homeostasis involved in gene transcription-associated events. Moreover, our findings strongly support the concept of the nucleus as an autonomous signaling compartment.Nitric oxide (NO) is a short-lived uncharged free radical involved in numerous complex biological processes such as blood pressure regulation, vascular inflammation, cell-mediated cytotoxicity, and survival (1, 2). One of the most biologically relevant actions of NO is its binding to the heme moiety in the heterodimeric enzyme soluble guanylate cyclase (sGC), 3 which leads to the production of the intracellular second messenger molecule cGMP and activation of cGMP-dependent protein kinases G (PKG). However, NO can also interact with and modify the bioactivity of a number of protein macromolecules through a series of reversible and nonreversible chemical reactions (e.g. S-, N-, and hemenitrosylation, tyrosine and tryptophan nitration) providing multifaceted regulatory mechanisms for cellular functions (3,4). NO is synthesized from L-arginine by a tripartite family of nitric-oxide synthase (NOS) isozymes composed of NOS-1 (nNOS), NOS-2 (iNOS), and NOS-3 (eNOS) originally found in brain, macrophages, and endothelium, respectively, and later discovered, for each NOS, in many other cell types (5).NOS isozymes, especially eNOS, are highly regulated by a number of mechanisms. Emerging findings show that eNOS bioactivity and mobilization to...

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“…Thus, to verify that the cytosolic ET-1-induced sustained increase in nuclear Ca 2+ in hVSMCs (Bkaily et al 2002 is mediated via activation of the R-type Ca 2+ channels, in these series of experiments we tested the effect of cytosolic ET-1 in sarcolemma-perforated hVSMCs pre-treated or not with PTX or CTX (Bkaily et al 1998(Bkaily et al , 2008. Figure 1 shows examples and Fig.…”

Section: Resultsmentioning

confidence: 98%

“…In the first series of experiments, pre-treatment with PTX and CTX was used to identify the R-type calcium channel, since the G-protein coupled to this type of channel is sensitive to both toxins (Bkaily et al 2002. Thus, to verify that the cytosolic ET-1-induced sustained increase in nuclear Ca 2+ in hVSMCs (Bkaily et al 2002 is mediated via activation of the R-type Ca 2+ channels, in these series of experiments we tested the effect of cytosolic ET-1 in sarcolemma-perforated hVSMCs pre-treated or not with PTX or CTX (Bkaily et al 1998(Bkaily et al , 2008.…”

Section: Resultsmentioning

confidence: 99%

Nuclear membrane R-type calcium channels mediate cytosolic ET-1-induced increase of nuclear calcium in human vascular smooth muscle cells

Bkaily

Avedanian

Al-Khoury

et al. 2015

Can. J. Physiol. Pharmacol.

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The objective of this work was to verify whether, as in the case of the plasma membrane of human vascular smooth muscle cells (hVSMCs), cytosolic ET-1-induced increase of nuclear calcium is mediated via the activation of calcium influx through the steady-state R-type calcium channel. Pharmacological tools to identify the R-type calcium channels, as well as real 3-D confocal microscopy imaging techniques coupled to calcium fluorescent probes, were used to study the effect of cytosolic ET-1 on nuclear calcium in isolated nuclei of human hepatocytes and plasma membrane perforated hVSMCs. Our results showed that pre-treatment with pertussis toxin (PTX) or cholera toxin (CTX) prevented cytosolic ET-1 (10(-9) mol/L) from inducing a sustained increase in nuclear calcium. Furthermore, the L-type calcium channel blocker nifedipine did not prevent cytosolic ET-1 from inducing an increase in nuclear calcium, as opposed to the dual L- and R-type calcium channel blocker isradipine (PN200-110) (in the presence of nifedipine). In conclusion, the preventative effect with PTX and CTX, and the absence of an effect with nifedipine, as well as the blockade by isradipine on cytosolic ET-1-induced increase in nuclear calcium, suggest that this nuclear calcium influx in hVSMCs is due to activation of the steady-state R-type calcium channel. The sarcolemmal and nuclear membrane R-type calcium channels in hVSMCs are involved in ET-1 modulation of vascular tone in physiology and pathology.

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Role of endothelin-1 receptors in the sarcolemma membrane and the nuclear membrane in the modulation of basal cytosolic and nuclear calcium levels in heart cells

Cited by 26 publications

References 17 publications

Whole-cell and nuclear NADPH oxidases levels and distribution in human endocardial endothelial, vascular smooth muscle, and vascular endothelial cells

Whole-cell and nuclear NADPH oxidases levels and distribution in human endocardial endothelial, vascular smooth muscle, and vascular endothelial cells

Nitric Oxide Signaling via Nuclearized Endothelial Nitric-oxide Synthase Modulates Expression of the Immediate Early Genes iNOS and mPGES-1

Nuclear membrane R-type calcium channels mediate cytosolic ET-1-induced increase of nuclear calcium in human vascular smooth muscle cells

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