Nox1,即NADPH氧化酶1,是NADPH氧化酶家族中的一个成员。NADPH氧化酶家族是一类能够跨膜转运电子并产生超氧化物和其他下游活性氧物质(ROS)的酶。Nox1主要在血管平滑肌细胞、内皮细胞和某些上皮细胞中表达,并在多种生理和病理过程中发挥作用,包括宿主防御、蛋白质的翻译后修饰、细胞信号传导、基因表达的调控以及细胞分化等[1,5]。Nox1的活性受到多种因素的调控,如细胞内钙离子水平、活性氧的产生和信号通路等。
Nox1在多种疾病的发生和发展中扮演着重要的角色。例如,在炎症性肠病(IBD)中,Nox1缺失导致ROS产生减少,进而影响肠道上皮细胞的分泌功能和M细胞的分化,导致炎症反应和免疫缺陷[2]。在帕金森病(PD)中,Nox1的表达和活性增加,促进了铁死亡相关神经退行性变的发生[3]。在血管损伤和动脉粥样硬化中,Nox1的表达和活性增加,导致血管炎症和氧化应激反应加剧,进而导致血管重构和动脉粥样硬化斑块的形成[4]。此外,Nox1还在糖尿病心肌病、肝内胆管癌、强迫症等疾病中发挥重要作用[6,7,8,9]。
综上所述,Nox1是一种重要的NADPH氧化酶,在多种生理和病理过程中发挥重要作用。Nox1的表达和活性受到多种因素的调控,并在多种疾病的发生和发展中扮演着重要的角色。深入研究Nox1的功能和调控机制,有助于我们更好地理解相关疾病的发病机制,并为开发新的治疗策略提供理论依据。
参考文献:
1. Bedard, Karen, Krause, Karl-Heinz. . The NOX family of ROS-generating NADPH oxidases: physiology and pathophysiology. In Physiological reviews, 87, 245-313. doi:. https://pubmed.ncbi.nlm.nih.gov/17237347/
2. Hsu, Nai-Yun, Nayar, Shikha, Gettler, Kyle, Chuang, Ling-Shiang, Cho, Judy H. 2022. NOX1 is essential for TNFα-induced intestinal epithelial ROS secretion and inhibits M cell signatures. In Gut, 72, 654-662. doi:10.1136/gutjnl-2021-326305. https://pubmed.ncbi.nlm.nih.gov/36191961/
3. Wang, Huiqing, Mao, Wenwei, Zhang, Yuhan, Cheng, Baohua, Yan, Fuling. 2024. NOX1 triggers ferroptosis and ferritinophagy, contributes to Parkinson's disease. In Free radical biology & medicine, 222, 331-343. doi:10.1016/j.freeradbiomed.2024.06.007. https://pubmed.ncbi.nlm.nih.gov/38876456/
4. Xu, Hu, Du, Shengnan, Fang, Bingying, Gustafsson, Jan-Åke, Guan, Youfei. 2019. VSMC-specific EP4 deletion exacerbates angiotensin II-induced aortic dissection by increasing vascular inflammation and blood pressure. In Proceedings of the National Academy of Sciences of the United States of America, 116, 8457-8462. doi:10.1073/pnas.1902119116. https://pubmed.ncbi.nlm.nih.gov/30948641/
5. Buvelot, Hélène, Jaquet, Vincent, Krause, Karl-Heinz. . Mammalian NADPH Oxidases. In Methods in molecular biology (Clifton, N.J.), 1982, 17-36. doi:10.1007/978-1-4939-9424-3_2. https://pubmed.ncbi.nlm.nih.gov/31172464/
6. Zhang, Qi, Zhou, Jixiang, Zhai, Denggao, Yang, Manyi, Zhou, Maojun. 2024. Gut microbiota regulates the ALK5/NOX1 axis by altering glutamine metabolism to inhibit ferroptosis of intrahepatic cholangiocarcinoma cells. In Biochimica et biophysica acta. Molecular basis of disease, 1870, 167152. doi:10.1016/j.bbadis.2024.167152. https://pubmed.ncbi.nlm.nih.gov/38582012/
7. Lankin, Vadim Z, Sharapov, Mars G, Tikhaze, Alla K, Konovalova, Galina G, Novoselov, Vladimir I. . Dicarbonyl-Modified Low-Density Lipoproteins Are Key Inducers of LOX-1 and NOX1 Gene Expression in the Cultured Human Umbilical Vein Endotheliocytes. In Biochemistry. Biokhimiia, 88, 2125-2136. doi:10.1134/S0006297923120143. https://pubmed.ncbi.nlm.nih.gov/38462455/
8. Zhang, Dandan, Li, Yilan, Wang, Weijie, Yan, Jingru, Zhang, Yao. 2022. NOX1 promotes myocardial fibrosis and cardiac dysfunction via activating the TLR2/NF-κB pathway in diabetic cardiomyopathy. In Frontiers in pharmacology, 13, 928762. doi:10.3389/fphar.2022.928762. https://pubmed.ncbi.nlm.nih.gov/36225554/
9. Asaoka, Nozomi. . [NOX1/NADPH Oxidase Facilitates Repetitive Behaviors by Enhancing D2 Receptor-mediated Synaptic Potentiation in the Striatum]. In Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan, 142, 1137-1143. doi:10.1248/yakushi.22-00125. https://pubmed.ncbi.nlm.nih.gov/36328442/