Polarity Protein Scrib Facilitates Endothelial Inflammatory Signaling

Kruse, Christoph; Kurz, Angela R.M.; Pálfi, Katalin; Humbert, Patrick O.; Sperandio, Markus; Brandes, Ralf P.; Fork, Christian; Michaelis, Uwe

doi:10.1161/atvbaha.115.305678

Cited by 7 publications

(9 citation statements)

References 53 publications

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“…7 , E–G ) was equally effective as the blocking peptides in reducing the interaction signal. The overall signal intensity in the experiments focusing on endogenous NOX4 was much lower than after overexpressing ( 35 ) the protein and required more amplification. Also the signal to background ratio was lower as the antibodies used were not made for immunofluorescence and as murine cells compared with human cells yield a different unspecific reaction pattern.…”

Section: Resultsmentioning

confidence: 93%

The Endoplasmic Reticulum Chaperone Calnexin Is a NADPH Oxidase NOX4 Interacting Protein

Prior

Wittig

Leisegang

et al. 2016

Journal of Biological Chemistry

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Within the family of NADPH oxidases, NOX4 is unique as it is predominantly localized in the endoplasmic reticulum, has constitutive activity, and generates hydrogen peroxide (H2O2). We hypothesize that these features are consequences of a so far unidentified NOX4-interacting protein. Two-dimensional blue native (BN) electrophorese combined with SDS-PAGE yielded NOX4 to reside in macromolecular complexes. Interacting proteins were screened by quantitative SILAC (stable isotope labeling of amino acids in cell culture) co-immunoprecipitation (Co-IP) in HEK293 cells stably overexpressing NOX4. By this technique, several interacting proteins were identified with calnexin showing the most robust interaction. Calnexin also resided in NOX4-containing complexes as demonstrated by complexome profiling from BN-PAGE. The calnexin NOX4 interaction could be confirmed by reverse Co-IP and proximity ligation assay, whereas NOX1, NOX2, or NOX5 did not interact with calnexin. Calnexin deficiency as studied in mouse embryonic fibroblasts from calnexin−/− mice or in response to calnexin shRNA reduced cellular NOX4 protein expression and reactive oxygen species formation. Our results suggest that endogenous NOX4 forms macromolecular complexes with calnexin, which are needed for the proper maturation, processing, and function of NOX4 in the endoplasmic reticulum.

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Section: Resultsmentioning

confidence: 93%

The Endoplasmic Reticulum Chaperone Calnexin Is a NADPH Oxidase NOX4 Interacting Protein

Prior

Wittig

Leisegang

et al. 2016

Journal of Biological Chemistry

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“…SCRIB, which is overexpressed in endothelial cells and is essential for planar cell polarity and serves as a novel proinflammatory regulator in endothelial cells ( 27 ). Altman and Kong ( 28 ) demonstrated that protein kinase C proteins (PKCs) serve essential roles in human immune disorders, and can be used as therapeutic targets in several immune disorders including autoimmune diseases.…”

Section: Discussionmentioning

confidence: 99%

Bioinformatics analysis to screen for critical genes between survived and non‑survived patients with sepsis

Zhang

et al. 2018

Mol Med Report

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Sepsis is a systemic inflammatory response syndrome, which is mostly induced by infection in the lungs, the abdomen and the urinary tract. The present study is aimed to investigate the mechanisms of sepsis. Expression profile of E-MTAB-4421 (including leukocytes isolated from 207 survived and 58 non-survived patients with sepsis) and E-MTAB-4451 (including leukocytes isolated from 56 survived and 50 non-survived patients with sepsis) were downloaded from the European Bioinformatics Institute database. Based on the E-MTAB-4421 expression profile, several differentially expressed genes (DEGs) were identified and performed with hierarchical clustering analysis by the limma and pheatmap packages in R. Using the BioGRID database and Cytoscape software, a protein-protein interaction (PPI) network was constructed for the DEGs. Furthermore, module division and module annotation separately were conducted by the Mcode and BiNGO plugins in Cytoscape software. Additionally, the support vector machine (SVM) classifier was constructed by the SVM function of e1071 package in R, and then verified using the dataset of E-MTAB-4451. A total of 384 DEGs were screened in the survival group. The PPI network was divided into 4 modules (modules A, B, C and D) involving 11 DEGs including microtubule-associated protein 1 light chain 3 alpha (MAP1LC3A), protein kinase C-alpha (PRKCA), metastasis associated 1 family member 3 (MTA3), and scribbled planar cell polarity protein (SCRIB). SCRIB and PRKCA in module B, as well as MAP1LC3A and MTA3 in module D, might function in sepsis through PPIs. Functional enrichment demonstrated that MAP1LC3A in module D was enriched in autophagy vacuole assembly. Finally, the SVM classifier could correctly and effectively identify the samples in E-MTAB-4451. In conclusion, DEGs such as MAP1LC3A, PRKCA, MTA3 and SCRIB may be implicated in the progression of sepsis, and need further and more thorough confirmation.

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“…Polarity proteins work by regulating many aspects of cellular differentiation and proliferation, including junctional protein formation and localization 101,102 . Although the understanding of polarity complexes is mainly supported by a wide range of experiments involving epithelial cells, the complexes also play pivotal roles in endothelial cells 103,104 . Thus, impairments to polarity complexes could subsequently result in damage to transmembrane and cytoplasmic junctional proteins.…”

Section: Sars-cov-2 Infection Induces a Cytokine Storm That Causes DImentioning

confidence: 99%

Hemorrhagic and ischemic stroke in patients with coronavirus disease 2019: incidence, risk factors, and pathogenesis - a systematic review and meta-analysis

et al. 2021

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Background: In this study, we aimed to determine the global prevalence, chronological order of symptom appearance, and mortality rates with regard to hemorrhagic and ischemic stroke in patients with coronavirus disease 2019 (COVID-19) and to discuss possible pathogeneses of hemorrhagic and ischemic stroke in individuals with the disease. Methods: We searched the PubMed, Scopus, and Web of Science databases for relevant articles published up to November 8, 2020. Data regarding study characteristics, hemorrhagic stroke, ischemic stroke, and COVID-19 were retrieved in accordance with the PRISMA guidelines. The Newcastle-Ottawa scale was used to assess the quality of the eligible studies. The pooled prevalence and mortality rate of hemorrhagic and ischemic stroke were calculated. Results: The pooled estimate of prevalence of hemorrhagic stroke was 0.46% (95% CI 0.40%–0.53%; I2=89.81%) among 67,155 COVID-19 patients and that of ischemic stroke was 1.11% (95% CI 1.03%–1.22%; I2=94.07%) among 58,104 COVID-19 patients. Ischemic stroke was more predominant (incidence: 71.58%) than hemorrhagic stroke (incidence: 28.42%) in COVID-19 patients who experienced a stroke. In COVID-19 patients who experienced a stroke, hospital admission with respiratory symptoms was more commonly reported than that with neurological symptoms (20.83% for hemorrhagic stroke and 5.51% for ischemic stroke versus 6.94% for hemorrhagic stroke and 5.33% for ischemic stroke, respectively). The pooled mortality rate of COVID-19 patients who experienced a hemorrhagic and ischemic stroke was 44.72% (95% CI 36.73%–52.98%) and 36.23% (95% CI 30.63%–42.24%), respectively. Conclusions: Although the occurrence of hemorrhagic and ischemic stroke is low, the mortality rates of both stroke types in patients with COVID-19 are concerning, and therefore, despite several potential pathogeneses that have been proposed, studies aimed at definitively elucidating the mechanisms of hemorrhagic and ischemic stroke in individuals with COVID-19 are warranted. PROSPERO registration: CRD42020224470 (04/12/20)

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Polarity Protein Scrib Facilitates Endothelial Inflammatory Signaling

Cited by 7 publications

References 53 publications

The Endoplasmic Reticulum Chaperone Calnexin Is a NADPH Oxidase NOX4 Interacting Protein

The Endoplasmic Reticulum Chaperone Calnexin Is a NADPH Oxidase NOX4 Interacting Protein

Bioinformatics analysis to screen for critical genes between survived and non‑survived patients with sepsis

Hemorrhagic and ischemic stroke in patients with coronavirus disease 2019: incidence, risk factors, and pathogenesis - a systematic review and meta-analysis

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