HIF-1α promotes paraquat induced acute lung injury and implicates a role NF-κB and Rac2 activity.

Autor: Zhu Y; Department of Critical Care Medicine, Shanghai General Hospital, Shanghai Jiaotong University, School of Medicine, Shanghai 201620, China., Meng X; Department of Critical Care Medicine, Shanghai General Hospital, Shanghai Jiaotong University, School of Medicine, Shanghai 201620, China., Yang W; Department of Critical Care Medicine, Shanghai General Hospital, Shanghai Jiaotong University, School of Medicine, Shanghai 201620, China., Wang J; Department of Critical Care Medicine, Shanghai General Hospital, Shanghai Jiaotong University, School of Medicine, Shanghai 201620, China., Zhang J; Department of Critical Care Medicine, Shanghai General Hospital, Shanghai Jiaotong University, School of Medicine, Shanghai 201620, China., Tian R; Department of Critical Care Medicine, Shanghai General Hospital, Shanghai Jiaotong University, School of Medicine, Shanghai 201620, China., Wang R; Department of Critical Care Medicine, Shanghai General Hospital, Shanghai Jiaotong University, School of Medicine, Shanghai 201620, China., Su Q; Department of Critical Care Medicine, Shanghai General Hospital, Shanghai Jiaotong University, School of Medicine, Shanghai 201620, China. Electronic address: suqi-4571@163.com., Jin W; Department of Critical Care Medicine, Shanghai General Hospital, Shanghai Jiaotong University, School of Medicine, Shanghai 201620, China. Electronic address: jinweishgh@163.com.
Jazyk: angličtina
Zdroj: Toxicology [Toxicology] 2023 Jan 01; Vol. 483, pp. 153388. Date of Electronic Publication: 2022 Nov 30.
DOI: 10.1016/j.tox.2022.153388
Abstrakt: Paraquat (PQ) is a bipyridine herbicide and oral exposure is the main way of PQ exposure with a very high mortality. At present, it is believed that large number of oxygen free radicals are generated and cause lipid peroxidation of tissue and organ cell membranes after PQ is absorbed. PQ exposure could cause multiple organ dysfunction, among which acute lung injury is the most common and most serious. However, its specific mechanism is still unclear. In this study, the C57BL/6J mouse (alveolar epithelial cell-specific knockout HIF-1α) model of acute lung injury (40 mg/kg PQ) at several time pointes and a model of acute type II alveolar epithelial cell (A549, 800 μM PQ) injury constructed. The oxidative stress (ROS, MDA) and inflammatory response (IL-1β, IL-6, TNF-α) were significantly inhibited in the alveolar epithelial cell-specific knockout of HIF-1α mice and siRNA technology to inhibit HIF-1α in alveolar epithelial cells. Further proteomic analysis showed that the expression of Rac2 protein, which is closely related to oxidative stress, was significantly increased after PQ exposure. And the inhibition of Rac2 expression in vitro significantly alleviated PQ-induced oxidative stress and inflammatory response. The expression of Rac2 protein was regulated by HIF-1α. The above suggests that HIF-1α may promote oxidative stress and inflammatory response in alveolar epithelial cells by regulating the expression of Rac2, and then participate in the promotion of PQ exposure-induced acute lung injury.
Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
Externí odkaz: