CD38 Mediates Angiotensin II–Induced Intracellular Ca<sup>2+</sup> Release in Rat Pulmonary Arterial Smooth Muscle Cells

Lee, Suengwon; Paudel, Omkar; Jiang, Yong-Liang; Yang, Xiao; Sham, James S.K.

doi:10.1165/rcmb.2014-0141oc

Cited by 31 publications

(26 citation statements)

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“…We also showed that ER Ca 2+ mobilization may be important because dantrolene, which blocks ryanodine receptor, reduced contraction only in Nox5 mice. Previous studies in coronary arterial myocytes and pulmonary arterial smooth muscle cells demonstrated that ryanodine receptor/Ca 2+ regulation involves ER‐associated Nox (2 and 4)‐derived ROS 43, 44. Our findings are supportive of this association, although the exact role of Nox5 in ER function warrants further investigation.…”

Section: Discussionsupporting

confidence: 83%

NADPH Oxidase 5 Is a Pro‐Contractile Nox Isoform and a Point of Cross‐Talk for Calcium and Redox Signaling‐Implications in Vascular Function

Montezano

Camargo

Persson

et al. 2018

JAHA

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BackgroundNADPH Oxidase 5 (Nox5) is a calcium‐sensitive superoxide‐generating Nox. It is present in lower forms and higher mammals, but not in rodents. Nox5 is expressed in vascular cells, but the functional significance remains elusive. Given that contraction is controlled by calcium and reactive oxygen species, both associated with Nox5, we questioned the role of Nox5 in pro‐contractile signaling and vascular function.Methods and ResultsTransgenic mice expressing human Nox5 in a vascular smooth muscle cell–specific manner (Nox5 mice) and Rhodnius prolixus, an arthropod model that expresses Nox5 endogenoulsy, were studied. Reactive oxygen species generation was increased systemically and in the vasculature and heart in Nox5 mice. In Nox5‐expressing mice, agonist‐induced vasoconstriction was exaggerated and endothelium‐dependent vasorelaxation was impaired. Vascular structural and mechanical properties were not influenced by Nox5. Vascular contractile responses in Nox5 mice were normalized by N‐acetylcysteine and inhibitors of calcium channels, calmodulin, and endoplasmic reticulum ryanodine receptors, but not by GKT137831 (Nox1/4 inhibitor). At the cellular level, vascular changes in Nox5 mice were associated with increased vascular smooth muscle cell [Ca2+]i, increased reactive oxygen species and nitrotyrosine levels, and hyperphosphorylation of pro‐contractile signaling molecules MLC20 (myosin light chain 20) and MYPT1 (myosin phosphatase target subunit 1). Blood pressure was similar in wild‐type and Nox5 mice. Nox5 did not amplify angiotensin II effects. In R. prolixus, gastrointestinal smooth muscle contraction was blunted by Nox5 silencing, but not by VAS2870 (Nox1/2/4 inhibitor).ConclusionsNox5 is a pro‐contractile Nox isoform important in redox‐sensitive contraction. This involves calcium‐calmodulin and endoplasmic reticulum–regulated mechanisms. Our findings define a novel function for vascular Nox5, linking calcium and reactive oxygen species to the pro‐contractile molecular machinery in vascular smooth muscle cells.

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Section: Discussionsupporting

confidence: 83%

NADPH Oxidase 5 Is a Pro‐Contractile Nox Isoform and a Point of Cross‐Talk for Calcium and Redox Signaling‐Implications in Vascular Function

Montezano

Camargo

Persson

et al. 2018

JAHA

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“…We have recently characterized the expression of CD38 and the CD38-dependent Ca 2+ response in PASMCs. We found that CD38 is highly expressed in PAs compared to other systemic arteries [47,48]. It plays important roles in Ca 2+ response activated by agonists, including angiotensin II, endothelin-1 and integrin-ligands through cADPR and NAADP-dependent mechanisms [47][48][49].…”

Section: +mentioning

confidence: 87%

“…We found that CD38 is highly expressed in PAs compared to other systemic arteries [47,48]. It plays important roles in Ca 2+ response activated by agonists, including angiotensin II, endothelin-1 and integrin-ligands through cADPR and NAADP-dependent mechanisms [47][48][49]. In particular, Ang II elicits CD38-dependent Ca 2+ release in PASMCs via PKC-dependent production of reactive oxygen species from NADPH oxidase 2 [48].…”

Section: +mentioning

confidence: 90%

“…It plays important roles in Ca 2+ response activated by agonists, including angiotensin II, endothelin-1 and integrin-ligands through cADPR and NAADP-dependent mechanisms [47][48][49]. In particular, Ang II elicits CD38-dependent Ca 2+ release in PASMCs via PKC-dependent production of reactive oxygen species from NADPH oxidase 2 [48]. We also detected the expression of the NAADP-sensitive twopore channels (TPC1 and TPC2) in PAs and PASMCs, and characterized the global and local Ca 2+ events elicited by NAADP from the endolysosomal stores [49].…”

Section: +mentioning

confidence: 99%

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Extracellular Adenosine Diphosphate Ribose Mobilizes Intracellular Ca2+ via Purinergic-Dependent Ca2+ Pathways in Rat Pulmonary Artery Smooth Muscle Cells

Huang

Subedi

et al. 2015

Cell Physiol Biochem

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Background/Aims: Adenosine diphosphate ribose (ADPR), a product of β-NAD⁺ metabolism generated by the multifunctional enzyme CD38, is recognized as a novel signaling molecule. The catalytic site of CD38 orients extracellularly or intracellularly, capable of generating ADPR outside and inside the cells. CD38-dependent pathways have been characterized in pulmonary artery smooth muscle cells (PASMCs); however the physiological function of extracellular ADPR is unclear. Methods: Ca²⁺ mobilizing and proliferative effects of extracellular ADPR were characterized and compared with the ATP-induced responses in rat PASMCs; and the expression of purinergic receptor (P2X and P2Y) subtypes were examined in pulmonary arteries. Results: ADPR elicited concentration-dependent increase in [Ca²⁺]_i with a fast transient and a sustained phase in PASMCs. The sustained phase was abolished by Ca²⁺ removal and inhibited by the non-selective cation channel blocker SKF-96365, but was unaffected by TRPM2 antagonists or nifedipine. The purinergic receptor (P2X) antagonist pyridoxal-phosphate-6-azophenyl-2', 4'-disulfonate inhibited partially the transient and the sustained Ca²⁺ response, while the P2(XY) inhibitor suramin and the phospholipase C inhibitor U73122 abolished the sustained Ca²⁺ influx. The P2Y1 antagonist MRS2179 had no effect on the response. By contrast, ATP and ADP activated Ca²⁺ response exhibited a high and a low affinity component, and the pharmacological profile of ATP-induced Ca²⁺ response was distinctive from that of ADPR. BrdU incorporation assay showed that ADPR caused significant inhibition whereas ATP caused slight stimulation of PASMC proliferation. RT-PCR analysis found that almost all P2X and P2Y subtypes are expressed in PAs. Conclusion: ADPR and ATP activate Ca²⁺ responses through different combinations of multiple purinergic receptor subtypes; and extracellular ADPR may exert an autocrine/paracrine action via purinergic receptors on PASMCs.

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“…Aldehyde dehydrogenase 1 family-member A1 (Aldh1a1), aldolase C-fructose-bisphosphate (Aldoc), and CD38 are oxygen-related enzymes, and Vegfa, Tgb2, and Ctgf are oxygen-related receptor ligands [21]. CD38 has been recently implicated to regulate Ca 2+ signaling in response to ROS generation in pulmonary arterial SMCs [74]. Therefore, it would be interesting to examine the importance of CD38 in the DA.…”

Section: Response To Oxygenmentioning

confidence: 99%

Unique Phenotypes of Endothelial Cells in Developing Arteries: A Lesson from the Ductus Arteriosus

Liu¹,

Minamisawa²

2017

Physiologic and Pathologic Angiogenesis - Signaling Mechanisms and Targeted Therapy

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Endothelial cells (ECs) play a critical role in regulating vascular pathophysiology. Various growth factors and relaxation factors such as vascular endothelial growth factor (VEGF) and nitric oxide (NO), which are derived from ECs, are known to maintain homeostasis and regulate vessel remodeling. Although the inner lumens of all types of vessels are covered by an EC monolayer, the characteristics of ECs difer in each tissue and developing stage of a vessel. Previously, we identiied the heterogeneity of ECs of the ductus arteriosus (DA) by analyzing its gene proiles. The DA is a fetal artery that closes immediately after birth due to the changes in concentrations of oxygen and vasoactive factors such as NO and prostaglandin E. Studying the unique gene proile of ECs in the DA can therefore uncover the novel key genes involved in developing vascular function and morphology such as O 2 sensitivity and physiological vascular remodeling. A comprehensive gene analysis identiied a number of genes related to morphogenesis and development in the DA. In this chapter, we discuss the heterogeneity of vascular ECs in the developing vessel in the DA.

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CD38 Mediates Angiotensin II–Induced Intracellular Ca²⁺ Release in Rat Pulmonary Arterial Smooth Muscle Cells

Abstract: inhibitors apocynin and diphenyleneiodonium, the NOX2-specific inhibitor gp91ds-tat, and the scavenger of reactive oxygen species (ROS) tempol. These results provide the first evidence that Ang II activates CD38-dependent Ca 21 release via the NOX2-ROS pathway in PASMCs.

Cited by 31 publications

References 50 publications

NADPH Oxidase 5 Is a Pro‐Contractile Nox Isoform and a Point of Cross‐Talk for Calcium and Redox Signaling‐Implications in Vascular Function

NADPH Oxidase 5 Is a Pro‐Contractile Nox Isoform and a Point of Cross‐Talk for Calcium and Redox Signaling‐Implications in Vascular Function

Extracellular Adenosine Diphosphate Ribose Mobilizes Intracellular Ca2+ via Purinergic-Dependent Ca2+ Pathways in Rat Pulmonary Artery Smooth Muscle Cells

Unique Phenotypes of Endothelial Cells in Developing Arteries: A Lesson from the Ductus Arteriosus

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CD38 Mediates Angiotensin II–Induced Intracellular Ca2+ Release in Rat Pulmonary Arterial Smooth Muscle Cells

Abstract: inhibitors apocynin and diphenyleneiodonium, the NOX2-specific inhibitor gp91ds-tat, and the scavenger of reactive oxygen species (ROS) tempol. These results provide the first evidence that Ang II activates CD38-dependent Ca 21 release via the NOX2-ROS pathway in PASMCs.

Cited by 31 publications

References 50 publications

NADPH Oxidase 5 Is a Pro‐Contractile Nox Isoform and a Point of Cross‐Talk for Calcium and Redox Signaling‐Implications in Vascular Function

NADPH Oxidase 5 Is a Pro‐Contractile Nox Isoform and a Point of Cross‐Talk for Calcium and Redox Signaling‐Implications in Vascular Function

Extracellular Adenosine Diphosphate Ribose Mobilizes Intracellular Ca2+ via Purinergic-Dependent Ca2+ Pathways in Rat Pulmonary Artery Smooth Muscle Cells

Unique Phenotypes of Endothelial Cells in Developing Arteries: A Lesson from the Ductus Arteriosus

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CD38 Mediates Angiotensin II–Induced Intracellular Ca²⁺ Release in Rat Pulmonary Arterial Smooth Muscle Cells