硝基苯代谢途径
中文名称
通路描述
硝基苯（硝基苯）是苯的衍生物，其苯环上连接有一个 NO2 基团。它是一种黄色的芳香液体，广泛用于香水工业，并大量用于制备苯胺。
英文描述
Turbulent (oscillatory, disturbed) flow shear stress activates signaling by PIEZO1 and integrins in endothelial cells Both turbulent (disturbed) flow and low laminar flow across epithelial cells initiate an inflammatory response that causes atherosclerosis (reviewed in Rahaman et al. 2023, Tamargo et al. 2023, Wang et al. 2023). In vivo, this process makes curved and branched regions of arteries especially prone to atherosclerosis.
In endothelial cells, fluid flow is sensed by mechanoresponsive membrane-localized PIEZO1 channels, which open and cause an influx of cations including calcium ions (Ca2+) (inferred from the mouse homolog in Conte et al. 2010). Intracellular Ca2+ activates the protease complex Calpain2, which cleaves Vinculin (VCL), a component of the peripheral cytoskeleton located between integrins and actin fibers (Miyazaki et al. 2007, 2010). Turbulent flow across endothelial cells also causes release of ATP by an uncharacterized mechanism (Albarrán-Juárez et al. 2018).
Through an uncharacterized PIEZO1-dependent mechanism, the phosphatase PTPN1 (PTP1B) is activated to dephosphorylate Annexin-2 (ANXA2), which relocalizes with integrins (ITGA5:ITGB1) to lipid rafts in the cell membrane (Zhang et al. 2020). The integrins recruit the phosphodiesterase PDE4D5 and the phosphatase PP2A, which activates PDE4D5 by dephosphorylating serine-715 and activates YAP1 by dephosphorylating serine-127 (inferred from mouse homologs in Yun et al. 2016). Activated PDE4D5 hydrolyzes cAMP and thereby increases inflammation. YAP1 is phosphorylated by ABL1 on tyrosine-407 and transits to the nucleus to activate pro-inflammatory genes (Li et al. 2019).
The kinase PTK2 (focal adhesion kinase, FAK) is phosphorylated, likely through autophosphorylation, and then activates pro-inflammatory NF-κB signaling through phosphorylation of CHUK (IKKA) (Dwyer et al. 2015) and RELA (Albarrán-Juárez et al. 2018). IKBKE is phosphorylated by an uncharacterized mechanism and phosphorylates STAT1, which dimerizes and transits to the nucleus to activate pro-inflammatory genes such as NLRP3 (Lv et al. 2024).
In endothelial cells, fluid flow is sensed by mechanoresponsive membrane-localized PIEZO1 channels, which open and cause an influx of cations including calcium ions (Ca2+) (inferred from the mouse homolog in Conte et al. 2010). Intracellular Ca2+ activates the protease complex Calpain2, which cleaves Vinculin (VCL), a component of the peripheral cytoskeleton located between integrins and actin fibers (Miyazaki et al. 2007, 2010). Turbulent flow across endothelial cells also causes release of ATP by an uncharacterized mechanism (Albarrán-Juárez et al. 2018).
Through an uncharacterized PIEZO1-dependent mechanism, the phosphatase PTPN1 (PTP1B) is activated to dephosphorylate Annexin-2 (ANXA2), which relocalizes with integrins (ITGA5:ITGB1) to lipid rafts in the cell membrane (Zhang et al. 2020). The integrins recruit the phosphodiesterase PDE4D5 and the phosphatase PP2A, which activates PDE4D5 by dephosphorylating serine-715 and activates YAP1 by dephosphorylating serine-127 (inferred from mouse homologs in Yun et al. 2016). Activated PDE4D5 hydrolyzes cAMP and thereby increases inflammation. YAP1 is phosphorylated by ABL1 on tyrosine-407 and transits to the nucleus to activate pro-inflammatory genes (Li et al. 2019).
The kinase PTK2 (focal adhesion kinase, FAK) is phosphorylated, likely through autophosphorylation, and then activates pro-inflammatory NF-κB signaling through phosphorylation of CHUK (IKKA) (Dwyer et al. 2015) and RELA (Albarrán-Juárez et al. 2018). IKBKE is phosphorylated by an uncharacterized mechanism and phosphorylates STAT1, which dimerizes and transits to the nucleus to activate pro-inflammatory genes such as NLRP3 (Lv et al. 2024).
所含基因
30 个基因