Human peroxidasin 1 promotes angiogenesis through ERK1/2, Akt, and FAK pathways

Medfai, Hayfa; Khalil, Alia; Rousseau, Alexandre Fontaine; Nuyens, Vincent; Paumann-Page, Martina; Sevcnikar, Benjamin; Furtmüller, Paul G.; Obinger, Christian; Moguilevsky, Nicole; Peulen, Olivier; Herfs, Michaël; Castronovo, Vincent; Amri, Mohamed; Antwerpen, Pierre Van; Vanhamme, Luc; Boudjeltia, Karim Zouaoui

doi:10.1093/cvr/cvy179

Cited by 29 publications

(23 citation statements)

References 47 publications

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“…The mechanism involves the oxidation of bromide to hypobromous acid (HOBr), which then promotes the cross link between specific methionine and hydroxylysine residues in the non-collagenous domain (NCD) to join two protomers of collagen IV (5). Other pathophysiological roles of peroxidasin have been suggested, such as antimicrobial defense (6,7), redox sensing through interaction with the transcription factor Nrf2 (8), promotion of angiogenesis (9) and kidney fibrosis (10,11). Homozygous deletion of peroxidasin causes eye defects (12) and high expression has been identified as a determinant of melanoma cell invasion (13).…”

Section: Introductionmentioning

confidence: 99%

Peroxidasin mediates bromination of tyrosine residues in the extracellular matrix

Bathish

Paumann-Page

Paton

et al. 2020

Journal of Biological Chemistry

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Peroxidasin is a heme peroxidase that oxidizes bromide to hypobromous acid (HOBr), a powerful oxidant that promotes the formation of the sulfilimine cross link in collagen IV in basement membranes. We investigated whether HOBr released by peroxidasin leads to other oxidative modifications of proteins, particularly bromination of tyrosine residues in peroxidasin-expressing PFHR9 cells. Using stable isotope dilution LC/MS/MS, we detected the formation of 3-bromotyrosine, a specific biomarker of HOBr-mediated protein modification. The level of 3-bromotyrosine in extracellular matrix proteins from normally cultured cells was 1.1 mmol/mol tyrosine and decreased significantly in the presence of the peroxidasin inhibitor, phloroglucinol. A negligible amount of 3-bromotyrosine was detected in peroxidasin-knockout cells. 3-Bromotyrosine formed both during cell growth in culture, and in the isolated decellularized extracellular matrix when embedded peroxidasin was supplied with hydrogen peroxide and bromide. The level of 3-bromotyrosine was significantly higher in extracellular matrix than intracellular proteins, although a low amount was detected intracellularly. 3-Bromotyrosine levels increased with higher bromide concentrations and decreased in the presence of physiological concentrations of thiocyanate and urate. However, these peroxidase substrates showed moderate to minimal inhibition of collagen IV cross-linking. Our findings provide evidence that peroxidasin promotes the formation of 3-bromotyrosine in proteins. They show that HOBr produced by peroxidasin is selective for, but not limited to, the cross-linking of collagen IV. Based on our findings, the use of 3-bromotyrosine as a specific biomarker of oxidative damage by HOBr warrants further investigation in clinical conditions linked to high peroxidasin expression.

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Section: Introductionmentioning

confidence: 99%

Peroxidasin mediates bromination of tyrosine residues in the extracellular matrix

Bathish

Paumann-Page

Paton

et al. 2020

Journal of Biological Chemistry

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“…VEGF downstream signaling pathways such as MAPKs, FAK, and AKT are known to regulate proliferation, migration, and tube formation (Cai et al, 2015; Medfai et al, 2019). For instance, ischemic stroke in adult mice is proven to be relieved by angiogenesis effect of PKM2 through activating the FAK signaling pathway (Chen et al, 2018).…”

Section: Discussionmentioning

confidence: 99%

“…Besides, evidence have suggested that increased levels of lactate due to accelerating glycolysis can promote angiogenesis through upregulating the expression of hypoxia‐inducible factor‐1α (HIF‐1α) and vascular endothelial growth factor (VEGF; Porporato et al, 2012). VEGF mainly interacts with vascular endothelial growth factor receptor 2 (VEGFR2) and activates multiple downstream pathways, such as mitogen‐activated protein kinases (MAPKs), focal adhesion kinase (FAK), and protein kinase B (AKT) signaling pathways, which are all known to regulate proliferation, migration, and tube formation during angiogenesis (Cai et al, 2015; Medfai et al, 2019). In addition, Tie2 is a receptor tyrosine kinase that is expressed primarily on ECs and is required for angiogenesis and for promoting vascular maturation (Zacharek et al, 2007).…”

Section: Introductionmentioning

confidence: 99%

PKM2 regulates angiogenesis of VR‐EPCs through modulating glycolysis, mitochondrial fission, and fusion

Ren

Guo

Shi

et al. 2020

Journal Cellular Physiology

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Vascular resident endothelial progenitor cells (VR-EPCs) have a certain ability to differentiate into endothelial cells (ECs) and participate in the process of angiogenesis. Glycolysis and mitochondrial fission and fusion play a pivotal role in angiogenesis. Pyruvate kinase muscle isoenzyme 2 (PKM2), which mediates energy metabolism and mitochondrial morphology, is regarded as the focus of VR-EPCs angiogenesis in our study. VR-EPCs were isolated from the hearts of 12-weeks-old Sprague-Dawley rats. The role of PKM2 on angiogenesis was evaluated by tube formation assay, wound healing assay, transwell assay, and chick chorioallantoic membrane assay. Western blot analysis, flow cytometry, mitochondrial membrane potential detection, reactive oxygen species (ROS) detection, immunofluorescence staining, and quantitative real-time polymerase chain reaction were used to investigate the potential mechanism of PKM2 for regulating VR-EPCs angiogenesis.We explored the function of PKM2 on the angiogenesis of VR-EPCs. DASA-58 (the activator of PKM2) promoted VR-EPCs proliferation and PKM2 activity, it also could promote angiogenic differentiation. At the same time, DASA-58 significantly enhanced glycolysis, mitochondrial fusion, slightly increased mitochondrial membrane potential, and maintained ROS at a low level. C3k, an inhibitor of PKM2, inhibited PKM2 activity, expression of angiogenesis-related genes and tube formation. Besides, C3k drastically reduced glycolysis and mitochondrial membrane potential while significantly promoting mitochondrial fission and ROS level.Activation of PKM2 could promote VR-EPCs angiogenesis through modulating glycolysis, mitochondrial fission and fusion. By contrast, PKM2 inhibitor has opposite effects.

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“…It is remarkable to note that aforementioned OSS and OD collections were successfully used in DP in the recent years to address tens of diverse biomedical research questions or to teach histology and pathology to thousands of biomedical students. QuPath desktop software was used in various fields including oncology and immunology (19), cardiovascular diseases (20), or multiple sclerosis (21) (see other publications at https://github.com/qupath/qupath/wiki/Citing-QuPath). Cytomine web application was used by researchers in various fields including machine/deep learning (22), learning analytics, image analysis in nephrology [e.g., when combined with Icy; (14)], osteoarthritis (23), or lung cancer (24) (see other publications at https://uliege.cytomine.org/#publications).…”

Section: Discussionmentioning

confidence: 99%

Open Practices and Resources for Collaborative Digital Pathology

Marée

2019

Front. Med.

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In this paper, we describe open practices and open resources in the field of digital pathology with a specific focus on approaches that ease collaboration in research and education settings. Our review includes open access journals and open peer review, open-source software (libraries, desktop tools, and web applications), and open access collections. We illustrate applications and discuss current limitations and perspectives.

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Human peroxidasin 1 promotes angiogenesis through ERK1/2, Akt, and FAK pathways

Abstract: Our findings suggest a role of enzymatically active peroxidasin 1 as a pro-angiogenic peroxidase and a modulator of ERK1/2, Akt and FAK signaling.

Cited by 29 publications

References 47 publications

Peroxidasin mediates bromination of tyrosine residues in the extracellular matrix

Peroxidasin mediates bromination of tyrosine residues in the extracellular matrix

PKM2 regulates angiogenesis of VR‐EPCs through modulating glycolysis, mitochondrial fission, and fusion

Open Practices and Resources for Collaborative Digital Pathology

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