title: Intermittent hypoxia-induced NF-κB and HO-1 regulation in human endothelial EA.hy926 cells.
abstract: Intermittent hypoxia (IH) is a hallmark feature in obstructive sleep apnea (OSA) which is increasingly recognized as an independent risk factor for atherosclerosis. Oxidative stress, inflammation, and cell apoptosis are major pathological events initiating or accelerating atherogenesis. This study addressed whether IH would affect these proatherogenic factors in endothelial cells and the mechanistic pathways involved. EA.hy926 cells were exposed to intermittent normoxia or IH for different numbers of cycles (32, 64, or 96). IH exposure time-dependently raised cellular GSSG/GSH ratio, increased production of IL-6 and IL-8, and accelerated cell apoptosis and death, concurrent with activation of NF-κB and inhibition of Nrf2/HO-1 pathways. At 64 cycles, inhibition of NF-κB attenuated IH-induced cellular oxidative stress and accumulation of inflammatory cytokines in cell culture medium but aggravated IH-induced cell apoptosis, while stimulation of HO-1 suppressed IH-induced cellular oxidative stress and cell apoptosis without affecting accumulation of inflammatory cytokines in cell culture medium. We demonstrated that early stage of exposure to IH-induced oxidative and inflammatory stresses leading to acceleration of cell apoptosis via NF-κB and Nrf2/HO-1 pathways in endothelial cells, suggesting the potential mechanisms for IH-induced vascular pathogenesis, in resemblance to OSA.
authors.affiliation: Department of Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Han
authors.forename: Sze Chun
authors.initials: SC
authors.lastname: Yeung
authors.forename: Mary Sau Man
authors.initials: MS
authors.lastname: Ip
authors.forename: Judith Choi Wo
authors.initials: JC
authors.lastname: Mak
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D050976:Basic-Leucine Zipper Transcription Factors / Q000172:deficiency / Q000235:genetics; D015687:Cell Hypoxia / Q000187:drug effects; D002460:Cell Line; D003470:Culture Media / Q000737:chemistry; D016207:Cytokines / Q000378:metabolism; D042783:Endothelial Cells / Q000166:cytology* / Q000187:drug effects; D051856:Fanconi Anemia Complementation Group Proteins / Q000172:deficiency / Q000235:genetics; D055785:Gene Knockdown Techniques; D051547:Heme Oxygenase-1 / Q000378:metabolism*; D006427:Hemin / Q000494:pharmacology; D006801:Humans; D051267:NF-E2-Related Factor 2 / Q000378:metabolism; D016328:NF-kappa B / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D018384:Oxidative Stress / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects; D013876:Thiophenes / Q000494:pharmacology
chemical_list: C102108:BACH1 protein, human; D050976:Basic-Leucine Zipper Transcription Factors; D003470:Culture Media; D016207:Cytokines; D051856:Fanconi Anemia Complementation Group Proteins; D051267:NF-E2-Related Factor 2; D016328:NF-kappa B; C495635:NFE2L2 protein, human; C477523:SC 514; D013876:Thiophenes; D006427:Hemin; C496541:HMOX1 protein, human; D051547:Heme Oxygenase-1