scholarly journals Neutrophil Cytosolic Factor 2

2020 ◽  
Author(s):  
Keyword(s):  
Cytosolic Factor

Abstract 23: Identification of NCF4 as a Novel Regulator in Arterial Remodeling and Advanced Atherosclerosis

2017 ◽  
Vol 37 (suppl_1) ◽  
Author(s):  
Alexandra Bäcklund ◽  
Karl Gertow ◽  
Hong Jin ◽  
Lina Olsson ◽  
Maria Gonzalez-Diez ◽  
...  
Keyword(s):  
Gene Product ◽  
Vascular Tissue ◽  
Intima Media Thickness ◽  
Carotid Intima Media Thickness ◽  
Functional Effect ◽  
Vessel Remodeling ◽  
Ros Formation ◽  
Cytosolic Factor ◽  
Stimulating Factor ◽  
Receptor Beta

Arterial wall remodeling is a central multifactorial process in the development and progression of cardiovascular diseases. We employed an approach aimed at observing genetic variants associated with the progression of carotid intima-media thickness (cIMT) in order to identify novel pathways effecting vessel remodeling. This was achieved by conducting gene-centric analysis of 400,000 variants in 3,042 subjects with repeated cIMT measurements. Rs16997464 on chr22 intergenic between neutrophil cytosolic factor-4 ( NCF4) and colony stimulating factor 2 receptor beta ( CSF2RB ) was associated with cIMT progression at array-wide significance (p <4.5x10 -7 ). The potential causative genes within this locus were investigated using a human vascular and non-vascular tissue biobank. Expression of 9 genes near rs16997464, were analyzed with the most significant association being with NCF4 in aortic adventitia. The effect of the variant on the function of the NCF4 gene product was further analyzed by comparing the oxidative burst capacity of neutrophils from subjects with different rs16997464 genotypes. We observed that neutrophils homozygous for the minor T allele, associated with slower cIMT progression, produced more extracellular ROS than neutrophils homozygous for the G allele, indicating a functional effect of rs16997464 on the NCF4 gene product p40 phox , a component of the NADPH oxidase 2 complex (NOX2). In parallel, we investigated if the chr22 locus also influenced the cellular composition of the atherosclerotic plaque, by utilizing data from the Athero-Express Biobank. Here we found that the minor T allele associated with a higher smooth muscle cell (SMC) content in the plaque. Finally, using a partial ligation model in mice where ncf4 is mutated, resulting in a reduced but not absent NOX2-associated ROS formation, we observed a reduced neointima formation in the ncf4 -mutated strain compared with wild-type littermates. Thus, this study identified rs16997464 in the NCF4-CSF2RB locus as a novel genetic determinant of cIMT progression, and provides evidence suggesting that NCF4 is involved in SMC proliferation and alteration of vessel wall pathophysiology.

scholarly journals ATP- and Cytosol-dependent Release of Adaptor Proteins from Clathrin-coated Vesicles: A Dual Role for Hsc70

1998 ◽  
Vol 9 (8) ◽  
pp. 2217-2229 ◽  
Author(s):  
Lisa A. Hannan ◽  
Sherri L. Newmyer ◽  
Sandra L. Schmid
Keyword(s):  
Plasma Membrane ◽  
Protein Complexes ◽  
Adaptor Protein ◽  
Adaptor Proteins ◽  
Dual Role ◽  
Vesicular Trafficking ◽  
Coated Vesicles ◽  
Golgi Network ◽  
Cytosolic Factor

Clathrin-coated vesicles (CCV) mediate protein sorting and vesicular trafficking from the plasma membrane and the trans-Golgi network. Before delivery of the vesicle contents to the target organelles, the coat components, clathrin and adaptor protein complexes (APs), must be released. Previous work has established that hsc70/the uncoating ATPase mediates clathrin release in vitro without the release of APs. AP release has not been reconstituted in vitro, and nothing is known about the requirements for this reaction. We report a novel quantitative assay for the ATP- and cytosol- dependent release of APs from CCV. As expected, hsc70 is not sufficient for AP release; however, immunodepletion and reconstitution experiments establish that it is necessary. Interestingly, complete clathrin release is not a prerequisite for AP release, suggesting that hsc70 plays a dual role in recycling the constituents of the clathrin coat. This assay provides a functional basis for identification of the additional cytosolic factor(s) required for AP release.

DEVELOPMENT AND APOPTOSIS OF PORCINE NUCLEAR TRANSFER EMBRYOS FUSED/ACTIVATED IN THE PRESENCE OF SPERM CYTOSOLIC FACTOR (SCF)

2007 ◽  
Vol 77 (Suppl_1) ◽  
pp. 221-221
Author(s):  
Joo Hyun Shim ◽  
In-Sun Hwang ◽  
Mi-Rung Park ◽  
Boh-Suk Yang ◽  
Dong-Il Jin ◽  
...  
Keyword(s):  
Nuclear Transfer ◽  
Cytosolic Factor

scholarly journals Impact of Donor Human Milk in the Preterm Very Low Birth Weight Gut Transcriptome Profile by Use of Exfoliated Intestinal Cells

Nutrients ◽  
2019 ◽  
Vol 11 (11) ◽  
pp. 2677 ◽  
Author(s):  
Anna Parra-Llorca ◽  
María Gormaz ◽  
Sheila Lorente-Pozo ◽  
Maria Cernada ◽  
Ana García-Robles ◽  
...  
Keyword(s):  
Human Milk ◽  
Preterm Infants ◽  
Very Low Birth Weight ◽  
Principal Component ◽  
Postnatal Period ◽  
Intestinal Cells ◽  
Donor Human Milk ◽  
Genome Wide ◽  
Alpha Gene ◽  
Cytosolic Factor

Background: Own mother’s milk (OMM) is the optimal nutrition for preterm infants. However, pasteurized donor human milk (DHM) is a valid alternative. We explored the differences of the transcriptome in exfoliated epithelial intestinal cells (EEIC) of preterm infants receiving full feed with OMM or DHM. Methods: The prospective observational study included preterm infants ≤ 32 weeks’ gestation and/or ≤1500 g birthweight. Total RNA from EEIC were processed for genome-wide expression analysis. Results: Principal component analysis and unsupervised hierarchical clustering analysis revealed two clustered groups corresponding to the OMM and DHM groups that showed differences in the gene expression profile in 1629 transcripts. The OMM group overexpressed lactalbumin alpha gene (LALBA), Cytochrome C oxidase subunit I gene (COX1) and caseins kappa gene (CSN3), beta gene (CSN2) and alpha gene (CSN1S1) and underexpressed Neutrophil Cytosolic Factor 1 gene (NCF1) compared to the DHM group. Conclusions: The transcriptomic analysis of EEIC showed that OMM induced a differential expression of specific genes that may contribute to a more efficient response to a pro-oxidant challenge early in the postnatal period when preterm infants are at a higher risk of oxidative stress. The use of OMM should be strongly promoted in preterm infants.

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