Effects of exogenous nicotinamide adenine dinucleotide (NAD+) in the rat heart are mediated by P2 purine receptors

Kuzmin, Vladislav S.; Pustovit, Ksenia B.; Abramochkin, Denis V.

doi:10.1186/s12929-016-0267-y

Cited by 12 publications

(10 citation statements)

References 46 publications

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“…55 The effects of nicotinamide adenine dinucleotide on the rat heart are mediated by P2 receptors. 56 Purinergic signaling seems to be involved in embryonic development of the heart. Activation by ATP and ADP promotes cardiomyogenesis of embryonic stem cells.…”

Section: Cardiac Actions Of Adenine Nucleosides and Nucleotidesmentioning

confidence: 99%

Purinergic Signaling in the Cardiovascular System

Burnstock

2017

Circulation Research

339

295

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Abstract:There is nervous control of the heart by ATP as a cotransmitter in sympathetic, parasympathetic, and sensory-motor nerves, as well as in intracardiac neurons. Centers in the brain control heart activities and vagal cardiovascular reflexes involve purines. Adenine nucleotides and nucleosides act on purinoceptors on cardiomyocytes, AV and SA nodes, cardiac fibroblasts, and coronary blood vessels. Vascular tone is controlled by a dual mechanism. ATP, released from perivascular sympathetic nerves, causes vasoconstriction largely via P2X1 receptors. Endothelial cells release ATP in response to changes in blood flow (via shear stress) or hypoxia, to act on P2 receptors on endothelial cells to produce nitric oxide, endothelium-derived hyperpolarizing factor, or prostaglandins to cause vasodilation. ATP is also released from sensory-motor nerves during antidromic reflex activity, to produce relaxation of some blood vessels. Purinergic signaling is involved in the physiology of erythrocytes, platelets, and leukocytes. ATP is released from erythrocytes and platelets, and purinoceptors and ectonucleotidases are expressed by these cells. P1, P2Y 1 , P2Y 12 , and P2X1 receptors are expressed on platelets, which mediate platelet aggregation and shape change. Long-term (trophic) actions of purine and pyrimidine nucleosides and nucleotides promote migration and proliferation of vascular smooth muscle and endothelial cells via P1 and P2Y receptors during angiogenesis, vessel remodeling during restenosis after angioplasty and atherosclerosis. The involvement of purinergic signaling in cardiovascular pathophysiology and its therapeutic potential are discussed, including heart failure, infarction, arrhythmias, syncope, cardiomyopathy, angina, heart transplantation and coronary bypass grafts, coronary artery disease, diabetic cardiomyopathy, hypertension, ischemia, thrombosis, diabetes mellitus, and migraine. (Circ Res. 2017;120:207-228.

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Section: Cardiac Actions Of Adenine Nucleosides and Nucleotidesmentioning

confidence: 99%

Purinergic Signaling in the Cardiovascular System

Burnstock

2017

Circulation Research

339

295

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“…Extracellular NAD + is an agonist of P2Y purinergic receptors [14,30]; these G protein-coupled receptors are linked to the activation of PLC followed by generation of the second messengers inositol 1,4,5-triphosphate (IP 3 ) and diacylglycerol (DAG) [31]. NAD + /P2Y receptors transfer signals through PLC [19,32]. Purinergic receptors are required for extracellular NAD + and evoke biological responses, which suggests that extracellular NAD + may be sensed by cell-surface receptors.…”

Section: Discussionmentioning

confidence: 99%

“…Extracellular NAD + induces signaling cascades by activating PLC via P2 receptors/Gq proteins [18,19]. To examine whether exogenous NAD + induces PLC activation, we measured the expression levels of PLC-δ3, PLC-γ2, and PLC-η2 in NAD + -treated cells by qPCR.…”

Section: Phospholipase C (Plc) Is Involved In Nad + -Induced Increasementioning

confidence: 99%

“…For example, ADP-ribose produced from NAD + is an agonist of the P2 purinergic receptor P2Y1 [17]. The family of P2 purinergic receptors is mainly coupled with G proteins that activate phospholipase C (PLC) [18,19].In our previous study, we found that oxyresveratrol, an antioxidant stilbenoid, stimulated MUC2 synthesis and increased NAD + levels by activating enzymes involved in the salvage pathways of NAD + biosynthesis in LS 174T goblet cells, revealing that NAD + plays a novel role in the formation of an intact intestinal mucus layer by stimulating mucin production [20]. Based on these data, we hypothesized that NAD + might be involved in MUC2 synthesis in the intestine.…”

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confidence: 99%

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Exogenous NAD+ Stimulates MUC2 Expression in LS 174T Goblet Cells via the PLC-Delta/PTGES/PKC-Delta/ERK/CREB Signaling Pathway

Yeom

Lim

2020

Biomolecules

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Background: MUC2, a major component of the mucus layer in the intestine, is associated with antimicrobial activity and gut immune system function. Currently, mucin is mainly known for its critical function in defense against toxic molecules and pathogens. In this study, we investigated the stimulatory effects of exogenous nicotinamide adenine dinucleotide (NAD + ) on the expression of MUC2 in LS 174T goblet cells. Methods: Genes related to MUC2 synthesis were measured by quantitative real-time PCR (qPCR). To analyze the gene expression profiles of NAD + -treated LS 174T goblet cells, RNA sequencing was performed. MUC2 expression in the cells and secreted MUC2 were measured by immunocytochemistry (ICC) and ELISA, respectively. Results: NAD + significantly stimulated MUC2 expression at mRNA and protein levels and increased the secretion of MUC2. Through RNA sequencing, we found that the expression of genes involved in arachidonic acid metabolism increased in NAD + -treated cells compared with the negative control cells. NAD + treatment increased phospholipase C (PLC)-δ and prostaglandin E synthase (PTGES) expression, which was inhibited by the appropriate inhibitors. Among the protein kinase C (PKC) isozymes, PKC-δ was involved in the increase in MUC2 expression. In addition, extracellular signal-regulated kinase (ERK)1/2 and cyclic AMP (cAMP) response element-binding protein (CREB) transcript levels were higher in NAD + -treated cells than in the negative control cells, and the enhanced levels of phosphorylated CREB augmented MUC2 expression. Conclusions: Exogenous NAD + increases MUC2 expression by stimulating the PLC-δ/PTGES/PKC-δ/ERK/CREB signaling pathway.Biomolecules 2020, 10, 580 2 of 18 contribute to chronic inflammation in the intestine [3]. Therefore, conservation of an intact mucus layer that properly regulates immune responses is a main factor that is necessary for the maintenance of intestinal homeostasis and the prevention of intestinal inflammatory diseases.MUC2 gene expression is regulated by cyclic AMP (cAMP) response element-binding protein (CREB) in retinoic acid-treated normal human tracheobronchial epithelial (NHTBE) cells [4]. CREB is a transcription factor regulating the expression of genes involved in a variety of cellular processes, such as cell growth and survival, differentiation, and mucin production [5]. Upon cAMP-induced phosphorylation through intracellular signaling cascades, CREB is activated and stimulates gene transcription by binding to the promoters of target genes. CREB phosphorylation through the mitogen-activated protein kinase (MAPK) signaling pathway is associated with various human diseases [5]. For example, angiotensin II induces cardiac fibrosis by enhancing periostin expression via the p38 MAPK-CREB pathway [6]. The protein kinase C (PKC)/p38 MAPK/CREB pathway is involved in membrane wound repair [7]. An E3 ubiquitin ligase (CUL4A) promotes the proliferation of cancer cells through the phosphorylation-mediated activation of ERK1/2 followed by CREB [8]. Paeoniflorin, der...

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Extracellular ATP and β-NAD alter electrical properties and cholinergic effects in the rat heart in age-specific manner

Pustovit

Потехина

Ivanova

et al. 2019

Purinergic Signalling

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Extracellular ATP and nicotinamide adenine dinucleotide (β-NAD) demonstrate properties of neurotransmitters and neuromodulators in peripheral and central nervous system. It has been shown previously that ATP and β-NAD affect cardiac functioning in adult mammals. Nevertheless, the modulation of cardiac activity by purine compounds in the early postnatal development is still not elucidated. Also, the potential influence of ATP and β-NAD on cholinergic neurotransmission in the heart has not been investigated previously. Age-dependence of electrophysiological effects produced by extracellular ATP and β-NAD was studied in the rat myocardium using sharp microelectrode technique. ATP and β-NAD could affect ventricular and supraventricular myocardium independent from autonomic influences. Both purines induced reduction of action potentials (APs) duration in tissue preparations of atrial, ventricular myocardium, and myocardial sleeves of pulmonary veins from early postnatal rats similarly to myocardium of adult animals. Both purine compounds demonstrated weak age-dependence of the effect. We have estimated the ability of ATP and β-NAD to alter cholinergic effects in the heart. Both purines suppressed inhibitory effects produced by stimulation of intracardiac parasympathetic nerve in right atria from adult animals, but not in preparations from neonates. Also, ATP and β-NAD suppressed rest and evoked release of acetylcholine (ACh) in adult animals. β-NAD suppressed effects of parasympathetic stimulation and ACh release stronger than ATP. In conclusion, ATP and β-NAD control the heart at the postsynaptic and presynaptic levels via affecting the cardiac myocytes APs and ACh release. Postsynaptic and presynaptic effects of purines may be antagonistic and the latter demonstrates agedependence.

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Effects of exogenous nicotinamide adenine dinucleotide (NAD+) in the rat heart are mediated by P2 purine receptors

Cited by 12 publications

References 46 publications

Purinergic Signaling in the Cardiovascular System

Purinergic Signaling in the Cardiovascular System

Exogenous NAD+ Stimulates MUC2 Expression in LS 174T Goblet Cells via the PLC-Delta/PTGES/PKC-Delta/ERK/CREB Signaling Pathway

Extracellular ATP and β-NAD alter electrical properties and cholinergic effects in the rat heart in age-specific manner

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