title: α-ENaC, a therapeutic target of dexamethasone on hydrogen sulfide induced acute pulmonary edema.
abstract: Acute pulmonary edema (APE) is one of the fatal outcomes after exposure to high levels of hydrogen sulfide (H2S), available evidence suggest that dexamethasone (DXM), a potent anti-inflammatory agent, has been widely used or proposed as a therapeutic approach for H2S-induced APE in clinical practice, however, the underlying mechanism remains poorly understood. Ample evidence suggest that epithelial Na(+) channel, especially for the subunit α-epithelial Na(+) channel (α-ENaC) plays a critical role in alveolar fluid clearance. Therefore, the present study is undertaken to investigate the effects of DXM on α-ENaC following H2S exposure. The Sprague Dawley rats were exposed to H2S to establish APE model, in parallel, A549 cells were treated with NaHS to establish cell model. In vivo study, we found that DXM significantly attenuated H2S-induced lung histopathological changes and alveolar fluid clearance decrement, however, these preventive effects of DXM can be obviously counteracted by the mifepristone (MIF), the glucocorticoid receptor (GR) blocker. Moreover, DXM markedly attenuated H2S-mediated α-ENaC down-regulation, and similarly, the process can be partially retarded by MIF. Furthermore, DXM obviously prevented H2S-mediated ERK1/2 activation both in vitro and in vivo study. These results, taken together, suggested that DXM exerted protective effects on H2S-induced APE, and α-ENaC might be a potential therapeutic target for APE induced by H2S.
authors.affiliation: Department of Emergency Medicine, the First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing, Jiangsu 210029, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Jiang
authors.affiliation: Key Lab of Modern Toxicology (NJMU), Ministry of Education, Department of Toxicology, School of Public Health, Nanjing Medical University, 818 Tianyuan East Road, Nanjing, Jiangsu 211166, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Emergency Medicine, the First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing, Jiangsu 210029, China.
authors.forename: Chenglei
authors.initials: C
authors.lastname: Su
authors.affiliation: Key Lab of Modern Toxicology (NJMU), Ministry of Education, Department of Toxicology, School of Public Health, Nanjing Medical University, 818 Tianyuan East Road, Nanjing, Jiangsu 211166, China.
authors.forename: Wenyi
authors.initials: W
authors.lastname: Qian
authors.affiliation: Department of Emergency Medicine, the First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing, Jiangsu 210029, China.
authors.forename: Junjie
authors.initials: J
authors.lastname: Chen
authors.affiliation: Department of Occupational Disease Prophylactico-Therapetic Institution, Jiangsu Provincial Center for Disease Prevention and Control, 122 Heban Cun, Nanjing, Jiangsu 210028, China.
authors.forename: Baoli
authors.initials: B
authors.lastname: Zhu
authors.affiliation: Department of Occupational Disease Prophylactico-Therapetic Institution, Jiangsu Provincial Center for Disease Prevention and Control, 122 Heban Cun, Nanjing, Jiangsu 210028, China.
authors.forename: Hengdong
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Key Lab of Modern Toxicology (NJMU), Ministry of Education, Department of Toxicology, School of Public Health, Nanjing Medical University, 818 Tianyuan East Road, Nanjing, Jiangsu 211166, China.
authors.forename: Hang
authors.initials: H
authors.lastname: Xiao
authors.affiliation: Department of Emergency Medicine, the First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing, Jiangsu 210029, China. Electronic address: zhangjsojz@163.com.
authors.forename: Jinsong
authors.initials: J
authors.lastname: Zhang
mesh_terms: D000818:Animals; D002460:Cell Line; D003907:Dexamethasone / Q000008:administration & dosage* / Q000494:pharmacology; D004195:Disease Models, Animal; D053503:Epithelial Sodium Channels / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects; D006862:Hydrogen Sulfide; D008168:Lung / Q000187:drug effects* / Q000473:pathology; D008297:Male; D015735:Mifepristone / Q000008:administration & dosage / Q000494:pharmacology; D020011:Protective Agents / Q000008:administration & dosage* / Q000494:pharmacology; D011654:Pulmonary Edema / Q000139:chemically induced* / Q000188:drug therapy* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D053503:Epithelial Sodium Channels; D020011:Protective Agents; C440894:Scnn1a protein, rat; D015735:Mifepristone; D003907:Dexamethasone; D006862:Hydrogen Sulfide
keywords: Acute pulmonary edema; Dexamethasone; ERK1/2; H(2)S; α-ENaC