An essential role of NAD(P)H oxidase 2 in UVA-induced calcium oscillations in mast cells

Li, Zhi Ying; Jiang, Weiwei; Cui, Zong Jie

doi:10.1039/c4pp00304g

Cited by 17 publications

(12 citation statements)

References 58 publications

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“…31 MC activation and proliferation are associated with enhanced reactive oxygen species (ROS) production mainly by using NADPH oxidase 2. 32,33 Furthermore, ROS play an important role in SM progression because they induce expression of the antiapoptotic protein DJ-1 in clonal MCs 34 ROS generation associated with MC proliferation could impair endotheliummediated dilation through several mechanisms, including (1) inhibition of vasodilator prostacyclin production, (2) uncoupling endothelial NO synthase, and (3) binding of NO with subsequent reduction of its bioavailability. 35 In patients with SM, univariate analysis shows that age, high serum tryptase levels, and flushing are associated with worse FMD, whereas MAP is directly related to FMD.…”

Section: Discussionmentioning

confidence: 99%

Flow-mediated dilation shows impaired endothelial function in patients with mastocytosis

Bucci¹,

Parente²,

Feo

et al. 2019

Journal of Allergy and Clinical Immunology

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Background: Mastocytosis is a rare disease characterized by clonal proliferation of mast cells (MCs) in different organs. Clinical manifestations of mastocytosis are mostly due to release of mediators from MCs and, in many cases, such as urticaria, flushing, angioedema, and anaphylaxis, are an expression of the biological effects of mediators on endothelial cells. Chronic secretion of mediators in patients with mastocytosis can lead to alteration of endothelial function. Objective: We sought to investigate endothelial function in patients with mastocytosis using a noninvasive technique of flow-mediated dilation (FMD). Methods: Twenty-five adult patients with indolent and advanced forms of mastocytosis and 20 healthy control subjects were enrolled in the study. Ultrasound assessment of FMD was performed by measuring changes in the diameter of the brachial artery after 5 minutes of arterial occlusion. Changes in FMD were correlated with clinical parameters and serum tryptase levels. Results: Patients with mastocytosis had lower FMD compared with healthy control subjects (P < .001). Advanced and smoldering forms showed a lower FMD compared with indolent forms (P < .001). FMD inversely correlated with age and serum tryptase levels and directly with median arterial pressure and recurrent flushing episodes. No correlation was found between FMD and osteoporosis, recurrent anaphylaxis, presence of skin lesions, and long-term antihistamine treatment. Conclusions: Endothelial dysfunction, as demonstrated by FMD reduction, is detectable in patients with mastocytosis and is more severe in patients with high tryptase levels and advanced disease. Endothelial function appears to be negatively influenced by MC proliferation rather than by the severity of mediatorrelated symptoms.

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Section: Discussionmentioning

confidence: 99%

Flow-mediated dilation shows impaired endothelial function in patients with mastocytosis

Bucci¹,

Parente²,

Feo

et al. 2019

Journal of Allergy and Clinical Immunology

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“…MCs, like keratinocytes, fibroblasts and several other cutaneous cells are also susceptible to low doses of narrowband (NB) UVB, making them targets of photons that lead to DNA damage and apoptosis . NAD(P)H oxidase 2 has been found important in UVA‐induced calcium oscillations and mediator production of mast cells . Whether or not MCs express photoreceptors, such as cryptochromes or opsins, remains to be investigated in detail.…”

Section: Effects Of Uvr On Mast Cellsmentioning

confidence: 99%

Ultraviolet radiation and skin mast cells: Effects, mechanisms and relevance for skin diseases

Siiskonen

Smorodchenko

Krause

et al. 2017

Experimental Dermatology

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Mast cells (MCs) are well known as versatile effector cells in allergic reactions and several other immune responses. Skin MCs and cutaneous MC responses are subject to the effects of environmental factors including ultraviolet radiation (UVR). Numerous studies have assessed the effects of UVR on MCs, in vitro and in vivo. Interestingly, UVR seems to have variable effects on non-activated and activated mast cells. In general, UV therapy is beneficial in the treatment of urticaria and mastocytosis, but the effects are variable depending on treatment regimen and type of UVR. Here, we review and summarise key reports from the older and current literature on the crosstalk of UVR and skin MCs. Specifically, we present the literature and discuss published reports on the effects of UVR on skin MCs in rodents and humans. In addition, we review the role of MCs in UVR-driven skin diseases and the influence of UV light on MC-mediated skin diseases. This summary of our current understanding of the interplay of skin MCs and UVR may help to improve the management of patients with urticaria and other MC disorders, to identify current gaps of knowledge, and to guide further research. K E Y W O R D Scancer, mast cell, ultraviolet radiation, urticaria

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“…Therefore, NOX2 and NOX2-associated signaling molecules may be good candidates for the targeted therapy of OS. NOX2 has been previously reported to be involved in a variety of physiological and pathological conditions, including prion disease (44)(45)(46)(47). NOX2 has also been implicated in cancer biology (48)(49)(50) as NOX2 was established to serve a pro-survival role in human leukemia and be involved to promote apoptosis in human glioma (48,50).…”

Section: Discussionmentioning

confidence: 99%

Inhibition of NADPH oxidase 2 induces apoptosis in osteosarcoma: The role of reactive oxygen species in cell proliferation

et al. 2018

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Abstract. Osteosarcomas (OS) are aggressive tumors that are characterized by dysregulated growth and resistance to apoptosis. Reactive oxygen species (ROS) are thought to be important signal transduction molecules in the regulation of cell growth. ROS-generating nicotinamide adenine dinucleotide phosphate oxidase (NOX) family enzymes have previously been suggested to be involved in neoplastic proliferation. To examine whether NOX-mediated generation of intracellular ROS confers anti-apoptotic activity, and thus a growth advantage, the current study first analyzed the mRNA expression of NOX family members by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) in five human OS cell lines. RT-PCR analysis revealed that NOX2 and NOX4 mRNAs were expressed in all the OS cell lines examined, whereas little or no NOX1 and NOX3 mRNAs were detected. By RT-qPCR, NOX2 mRNA expression levels were demonstrated to be higher than NOX4 mRNA expression levels. The viability of OS cells decreased in a dose-dependent manner with treatment of diphenylene iodonium (DPI), an inhibitor of flavoprotein-dependent oxidase. DPI treatment was observed to reduce intracellular ROS levels by ~50%, and increase the frequency of apoptosis by 30%. Notably, small interfering RNAs (siRNAs) targeting NOX2 significantly suppressed ROS generation; ROS depletion by DPI or NOX2 siRNAs induced apoptosis in OS cells. Together, the results of the present study indicate that NOX2-mediated ROS generation promotes cell survival and ROS depletion leads to apoptosis, thus highlighting the NOX2-ROS signaling pathway as a potential therapeutic target for OS treatment.

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An essential role of NAD(P)H oxidase 2 in UVA-induced calcium oscillations in mast cells

Cited by 17 publications

References 58 publications

Flow-mediated dilation shows impaired endothelial function in patients with mastocytosis

Flow-mediated dilation shows impaired endothelial function in patients with mastocytosis

Ultraviolet radiation and skin mast cells: Effects, mechanisms and relevance for skin diseases

Inhibition of NADPH oxidase 2 induces apoptosis in osteosarcoma: The role of reactive oxygen species in cell proliferation

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