Mechanisms underlying unidirectional laminar shear stress-mediated Nrf2 activation in endothelial cells: Amplification of low shear stress signaling by primary cilia
| Autor: | Giovanni E. Mann, Tetsuro Ishii, Eiji Warabi |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
Medicine (General)
Endothelial cells Clinical Biochemistry Cell FGF-2 FGF-2 fibroblast growth factor-2 Review Article HO-1 heme oxygenase 1 Biochemistry nSMase2 neutral sphingomyelinase 2 miR microRNA Mrp1 multidrug resistance protein 1 NOXA1 NOX activator 1 PAR1 proteinase-activated receptor-1 Neurotrophic factors Elastase KLF2 Krüppel-like factor 2 CIC-3 chloride channel 3 Biology (General) Cells Cultured NOX1 NADPH oxidase 1 Chemistry eNOS endothelial nitric oxide synthase Cx43 connexin 43 VEGF vascular endothelial growth factor Cell biology Keap1 Kelch-like ECH-associated protein 1 MMP matrix metalloproteinase medicine.anatomical_structure BDNF brain-derived neurotrophic factor PGD2 prostaglandin D2 HB-EGF heparan-binding epidermal growth factor-like growth factor Cilium OSS oscillatory shear stress QH301-705.5 NF-E2-Related Factor 2 NAD + nicotine amido adenine dinucleotide IGF-1 insulin-like growth factor-1 USS unidirectional shear stress Exocytosis Nrf2 NOXO1 NOX organizer 1 Glycocalyx 15d-PGJ2 15-Deoxy-Δ12 14-prostaglandin J2 R5-920 medicine Shear stress HUVEC human umbilical vein endothelial cells Secretion Cilia Fibroblast Transcription factor XO xanthine oxidase Organic Chemistry PSA-NCAM polysialylated neural cell adhesion molecule RyR ryanodine receptor XD xanthine dehydrogenase EGFR epidermal growth factor receptor CK2 casein kinase 2 NF-κB nuclear factor κ-light chain enhancer of activated B cells Oxidative Stress AMPK AMP-activated protein kinase Stress Mechanical Nrf2 nuclear factor-E2-related factor 2 Cav1 caveolin-1 |
| Zdroj: | Redox Biology Redox Biology, Vol 46, Iss, Pp 102103-(2021) |
| ISSN: | 2213-2317 |
| Popis: | Endothelial cells are sensitive to mechanical stress and respond differently to oscillatory flow versus unidirectional flow. This review highlights the mechanisms by which a wide range of unidirectional laminar shear stress induces activation of the redox sensitive antioxidant transcription factor nuclear factor-E2-related factor 2 (Nrf2) in cultured endothelial cells. We propose that fibroblast growth factor-2 (FGF-2), brain-derived neurotrophic factor (BDNF) and 15-Deoxy-Δ12,14-prostaglandin J2 (15d-PGJ2) are potential Nrf2 activators induced by laminar shear stress. Shear stress-dependent secretion of FGF-2 and its receptor-mediated signaling is tightly controlled, requiring neutrophil elastase released by shear stress, αvβ3 integrin and the cell surface glycocalyx. We speculate that primary cilia respond to low laminar shear stress (15 dyn/cm2) induces vesicular exocytosis of BDNF from endothelial cells, and we propose that BDNF via the p75NTR receptor could induce CK2-mediated Nrf2 activation. Unidirectional laminar shear stress upregulates gene expression of FGF-2 and BDNF and generation of 15d-PGJ2, which cooperate in sustaining Nrf2 activation to protect endothelial cells against oxidative damage. Graphical abstract Image 1 Highlights • Primary cilia amplify low unidirectional shear stress signals in endothelial cells. • Low shear stress induces release of IGF-1 and neutrophil elastase. • IGF-1 and elastase cooperate in upregulating FGF-2 gene expression and secretion. • Glycocalyx facilitates FGF-2 secretion, trapping, expression and receptor signaling. • FGF-2, BDNF and 15d-PGJ2 are shear stress-related potential Nrf2 activators. |
| Databáze: | OpenAIRE |
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