氮氧化物1
NADPH氧化酶
氮氧化物4
细胞生物学
芳香烃受体
生物
活性氧
转录因子
信号转导
生物化学
基因
作者
Kyoung Ah Kang,Mei Jing Piao,Pincha Devage Sameera Madushan Fernando,Herath Mudiyanselage Udari Lakmini Herath,Joo Mi Yi,You‐Jin Jeon,Young Youl Hyun,Kelun Zhang,Chang Ook Park,Jin Won Hyun
标识
DOI:10.1016/j.envpol.2024.123675
摘要
Stimulation of human keratinocytes with particulate matter 2.5 (PM2.5) elicits complex signaling events, including a rise in the generation of reactive oxygen species (ROS). However, the mechanisms underlying PM2.5-induced ROS production remain unknown. Here, we show that PM2.5-induced ROS production in human keratinocytes is mediated via the NADPH oxidase (NOXs) system and the Ca2+ signaling pathway. PM2.5 treatment increased the expression of NOX1, NOX4, and a calcium-sensitive NOX, dual oxidase 1 (DUOX1), in human epidermal keratinocyte cell line. PM2.5 bound to aryl hydrocarbon receptor (AhR), and this complex bound to promoter regions of NOX1 and DUOX1, suggesting that AhR acted as a transcription factor of NOX1 and DUOX1. PM2.5 increased the transcription of DUOX1 via epigenetic modification. Moreover, a link between DNA demethylase and histone methyltransferase with the promoter regions of DUOX1 led to an elevation in the expression of DUOX1 mRNA. Interestingly, PM2.5 increased NOX4 expression and promoted the interaction of NOX4 and Ca2+ channels within the cytoplasmic membrane or endoplasmic reticulum, leading to Ca2+ release. The increase in intracellular Ca2+ concentration activated DUOX1, responsible for ROS production. Our findings provide evidence for a PM2.5-mediated ROS-generating system network, in which increased NOX1, NOX4, and DUOX1 expression serves as a ROS signal through AhR and Ca2+ activation.
科研通智能强力驱动
Strongly Powered by AbleSci AI