NCF2

Last update 08 May 2025

Basic Info

Synonyms

67 kDa neutrophil oxidase factor, NADPH oxidase activator 2, NCF-2

+ [7]

Introduction

Subunit of the phagocyte NADPH oxidase complex that mediates the transfer of electrons from cytosolic NADPH to O2 to produce the superoxide anion (O2(-)) (PubMed:12207919, PubMed:38355798). In the activated complex, electrons are first transferred from NADPH to flavin adenine dinucleotide (FAD) and subsequently transferred via two heme molecules to molecular oxygen, producing superoxide through an outer-sphere reaction (PubMed:38355798). Activation of the NADPH oxidase complex is initiated by the assembly of cytosolic subunits of the NADPH oxidase complex with the core NADPH oxidase complex to form a complex at the plasma membrane or phagosomal membrane (PubMed:38355798). This activation process is initiated by phosphorylation dependent binding of the cytosolic NCF1/p47-phox subunit to the C-terminus of CYBA/p22-phox (By similarity).

100 Clinical Results associated with NCF2

100 Translational Medicine associated with NCF2

0 Patents (Medical) associated with NCF2

1,345

Literatures (Medical) associated with NCF2

01 May 2025·Cell Reports

Single-cell and spatial transcriptomics reveal the pathogenesis of chronic granulomatous disease in a natural model

Article

Author: Wang, Shanshan ; Ding, Jiayu ; Jiao, Shaozhuo ; Zhang, Guorong ; Zhou, Zhiliang ; Dong, Ge ; Zhao, Zilong ; Liu, Jingjing ; Ma, Yunxi ; Ma, Tianrui ; Cai, Zhigang ; Yu, Hanzhi

Genetic defects in NADPH oxidase 2 (NOX2) cause chronic granulomatous disease (CGD), which is characterized by increased susceptibility to infections and excessive inflammation leading to granuloma formation. We developed a CGD model using Ncf2^-/- mice through controlled environmental exposure. Unlike in specific-pathogen-free environments, these mice spontaneously developed pulmonary granulomas under clean-grade conditions. In the affected lung tissue, significant changes in microbial communities were observed, accompanied by the infiltration of neutrophils and monocyte-derived macrophages (MDMs). Specific nitric oxide synthase 2 (NOS2)^high neutrophils with a pro-inflammatory transcriptional profile localize at the granuloma core, while an MDM subpopulation marked by MMP12 at the periphery exhibits a pro-fibrotic signature. Pharmacological inhibition of macrophage migration inhibitory factor (MIF), deletion of the pro-survival gene myeloid RNA regulator of Bim-induced death (Morrbid), and knockout of Il1r1 all suppressed granuloma formation by mitigating inflammation. This study underscores the establishment of a natural CGD model through environmental control, elucidates the mechanisms of granuloma formation, and develops potent therapeutic interventions.

01 May 2025·Phytomedicine

Stachydrine hydrochloride reduces NOX2 activity to suppress oxidative stress levels to improve cardiac insufficiency

Article

Author: Chen, Huihua ; Xu, Ming ; Lu, Rong ; Guo, Shuting ; Zhang, Chen ; Guo, Wei ; Shan, Xiaoli ; Fu, Mengwei ; Yang, Kaijing ; Li, Rongshan ; Zhao, Pei ; Yang, Songru

BACKGROUNDOxidative stress is a significant cause in the occurrence of cardiac insufficiency. Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase2 (NOX2)-derived reactive oxygen species (ROS) play a pivotal role in oxidative stress-induced excitation-contraction decoupling. Stachydrine hydrochloride (Sta) reduces pressure overload-induced cardiac insufficiency, which may be related to the NOX2-ROS pathway, as demonstrated by our earlier research. However, the mechanism through which Sta specifically affects NOX2 remains unknown.PURPOSEIn order to investigate whether Sta plays a cardioprotective role by inhibiting NOX2 activity, we explored the specific mechanism by which Sta improves cardiac function by affecting NOX2-mediated oxidative stress in this study.METHODSMolecular docking and cellular thermal shift assay (CETSA) were performed to verify whether Sta can bind to individual subunits of NOX2. We induced models of cardiac insufficiency in the compensatory phase (cardiac hypertrophy) by phenylephrine (PE) in vivo and in vitro and treated with Sta and GSK2795039 (NOX2 inhibitor). Cardiac function and structure were observed by echocardiography analysis. We detected the expression and localization of NOX2 subunits and calcium channel proteins, also detected the activities of ROS and NOX2, SOD, and GSH, and observed intracardiac calcium homeostasis and systolic-diastolic function in cardiomyocytes. Secondly, we used adenovirus and adeno-associated virus transfection for cardiac-specific overexpression of NOX2 in vivo and in vitro respectively, and also treated with Sta to observe NOX2 activation indexes and ROS levels, cardiac function and cardiomyocyte function in mice.RESULTSPrior to our investigation, we discovered that Sta could bind to NOX2 through molecular docking and CETSA. The findings demonstrated that Sta decreased the expression levels of gp91^phox and p67^phox, as well as the phosphorylation levels of p47^phox, and by preventing p67^phox and p47^phox from translocating across cell membranes. NOX2 activity inhibition by Sta suppresses ROS production. Sta reduced ROS-induced oxidation of Ca²⁺/calmodulin protein kinase II and modulated excitatory-contractile coupling via sarcoplasmic reticulum calcium pumps. Cardiac-specific overexpression of gp91^phox promotes membrane translocation of p67^phox and p47^phox, increases NOX2 activity, and promotes ROS generation. Sta inhibition of gp91^phox overexpression reduced the membrane translocation of p67^phox and p47^phox, decreased NOX2 activity and oxidative stress levels, and restored excitatory-contractor-coupled myocardial function.CONCLUSIONSOur study innovatively verified the key role of NOX2 in cardiac insufficiency. Sta downgrades NOX2's activity by suppressing the protein level of gp91^phox and the membrane transport of p67^phox and p47^phox, thereby reducing myocardial oxidative stress and playing a cardioprotective role. This study was hoped to support the possibility of Sta as a cardiac function-enhancing drug in the future.

01 Apr 2025·Gene

Identification of novel hub gene and biological pathways associated with ferroptosis in In-Stent restenosis

Article

Author: Zhang, Meixia ; Guo, Yunmiao ; Huang, Siming ; Xu, Huiling ; Pang, Lijuan ; Du, Jin ; Zhao, Xia ; Cai, Wenping ; Qiu, Jin ; Tao, Lin ; Jin, Shan ; Xu, Lingli

BACKGROUNDIn-stent restenosis (ISR) is one of the most significant complications following percutaneous coronary intervention (PCI) in patients with coronary artery disease (CAD). Ferroptosis is a novel cell death mode characterized by iron overload and lipid peroxidation. However, the role of ferroptosis in vascular smooth muscle cells (VSMCs) regulating neointimal formation during restenosis remains unclear.OBJECTIVEThe current study aims to reveal the molecular targets for neointimal hyperplasia through integrated analysis of data from gene expression omnibus (GEO) databases and single-cell sequencing (scRNA-Seq).METHODS AND RESULTSIn this study, we screened ten common differentially expressed genes (Co-DEGs) including BID, SP1, NCF2, HERPUD1, RICTOR, LAMP2, CAT, ACSL1, CS, and ANO6 from the GEO and FerrDb V2. GO/KEGG analyses indicated that metabolic reactions, particularly glyoxylate and dicarboxylate metabolism pathways, are the main molecular events. Immune infiltration analysis showed significant correlations between the expression of Co-DEGs and the infiltration of macrophages, dendritic cells, eosinophils, and neutrophils. Moreover, we identified SP1 as a potential therapeutic target associated with ferroptosis in ISR and constructed a lncRNA-miRNA-SP1 regulatory network. Using scRNA-Seq data to validate the expression of Co-DEGs in the neointima, we found that metabolic pathways such as carbon metabolism, peroxisomes, and reactive oxygen species were enriched. Immune infiltration examined the relationship between Co-DEGs and immune cells, revealing negative correlation between SP1 and neutrophils, and positive correlation between BID and macrophages.CONCLUSIONThe integrated analyses identified SP1 as a key regulator of ferroptosis in ISR and proposed its potential to be a novel therapeutic target of ISR. The construction of ceRNA network based on SP1 might contribute to new treatment strategy and drug development for ISR.

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