|本期目录/Table of Contents|

[1]赵世鸿,陈 键,高嘉营,等.铁死亡在海水诱导支气管上皮细胞损伤中的作用研究[J].中华肺部疾病杂志,2023,(06):756-760.[doi:10.3877/cma.j.issn.1674-6902.2023.06.002]
　Zhao Shihong,Chen Jian,Gao Jiaying,et al.Effectof ferroptosis onseawater-induced bronchial epithelial cells injury[J].,2023,(06):756-760.[doi:10.3877/cma.j.issn.1674-6902.2023.06.002]
点击复制

铁死亡在海水诱导支气管上皮细胞损伤中的作用研究(PDF)

《中华肺部疾病杂志》[ISSN:1006-6977/CN:61-1281/TN]

卷:
期数:
2023年06期
页码:
756-760
栏目:
论著
出版日期:
2023-12-20

文章信息/Info

Title:
Effectof ferroptosis onseawater-induced bronchial epithelial cells injury
作者:
赵世鸿; 陈 键; 高嘉营; 金发光
710038 西安,空军军医大学第二附属医院呼吸与危重症医学科
Author(s):
Zhao Shihong;  Chen Jian;  Gao Jiaying;  Jin Faguang.
Department of Respiratory and Critical Care Medicine, The Second Affiliated Hospital of Air Force Medical University, Xi'an 710038, China
关键词:
海水淹溺;  急性肺损伤;  铁死亡;  支气管上皮细胞
Keywords:
Seawater;  Acute lung injury;  Ferroptosis;  Bronchial epithelial cells
分类号:
R563
DOI:
10.3877/cma.j.issn.1674-6902.2023.06.002
摘要:
目的 分析铁死亡(ferroptosis)在海水暴露后支气管上皮细胞损伤中的作用。方法 将培养至对数生长期的人支气管上皮细胞分为四组:Con(Control)组,SW(Seawater)组,Con+F(Fer-1)组,SW+F组。Con组使用DMEM完全培养基进行培养,Con+F组使用含有10 μM Fer-1的DMEM完全培养基培养6 h,SW组使用含有25.0%中国一级标准海水的DMEM完全培养基培养6 h,SW+F组使用含有10 μM Fer-1的25.0%一级标准海水DMEM完全培养基培养6 h。后检测每组细胞的增殖活力,测定GSH、MDA的含量,SOD的活力,并用蛋白免疫印迹检测GPX4、FTH1、COX2、ACSL4的相对蛋白表达量。结果 海水组的细胞活性显著下降(P<0.0001),呈时间依赖性,平均每两小时下降13.0%,而Fer-1能够显著改善细胞活性的下降(P<0.0001),相对活性升高8.897%。Fer-1可显著缓解海水诱导的细胞GSH降低、MDA积累和SOD活力降低(P<0.001),Fer-1处理后相较于海水组分别升高3.985 μmol/gprot,降低1.414 nM/mgprot,升高1.288 U/mgprot。并可减轻海水诱导的细胞FTH1、GPX4表达量的降低,以及COX2、ACSL4表达量的升高(P<0.05),分别相对升高25.02%、29.84%,降低68.98%、39.17%。结论 海水暴露使支气管上皮细胞发生铁死亡,Fer-1可减轻海水诱导的支气管上皮细胞损伤。
Abstract:
Objective This study aims to investigate the role of ferroptosis in human bronchial epithelial cells injury following exposure to seawater. Methods bronchial epithelial cells were cultured to the logarithmic growth phase and divided into four groups: Control(Con), Seawater treated(SW), Fer-1 treated control(Con+F), and Fer-1 treated seawater(SW+F)groups. The Con group was cultured with DMEM complete medium, the Con+F group was cultured with DMEM complete medium containing 10 μM Fer-1 for 6 hours, the SW group was cultured with DMEM complete medium containing 25% Chinese primary standard seawater for 6 hours, and the SW+F group was cultured with DMEM complete medium containing 25% primary standard seawater and 10 μM Fer-1 for 6 hrs. Subsequently, the cell viability, GSH and MDA levels, SOD vigor, and protein expression levels of GPX4, FTH1, COX2, and ACSL4 were measured. Results The viability of cells in the seawater group significantly decreased(P<0.0001), following a time-dependent pattern, with an average decrease of 13% every two hours. However, treatment with Fer-1 was able to significantly ameliorate this decline in cell viability(P<0.0001), resulting in a relative increase of 8.897%. Moreover, Fer-1 was capable of significantly mitigating the reduction in cellular GSH, MDA accumulation, and SOD activity induced by seawater(P<0.001). Compared to the seawater group, treatment with Fer-1 led to an increase of 3.985 μmol/gprot, a decrease of 1.414 nM/mgprot, and an increase of 1.288 U/mgprot. Furthermore, Fer-1 was able to mitigate the reduction in cellular FTH1 and GPX4 expression levels and the increase in COX2 and ACSL4 expression levels induced by seawater(P<0.05), resulting in relative increases of 25.02% and 29.84% and reductions of 68.98% and 39.17%, respectively. Conclusion Seawater exposure induces ferroptosis in bronchial epithelial cells, while Fer-1 attenuates the seawater-induced cell injury.

参考文献/References:

1 Organization WH, Bloomberg LP. Global report on drowning:preventing a leading killer[M]. World Health Organization, 2014.
2 李聪聪, 薄丽艳, 李艳燕, 等. 海水吸入型肺损伤中蛋白激酶SPAK的表达改变[J/CD]. 中华肺部疾病杂志(电子版), 2021, 15(2): 152-157.
3 Santagostino SF, Assenmacher CA, Tarrant JC, et al. Mechanisms of Regulated Cell Death: Current Perspectives[J]. Vet Pathol, 2021, 58(4): 596-623.
4 Woo Y, Lee HJ, Jung YM, et al. Regulated necrotic cell death in alternative tumor therapeutic strategies[J]. Cells, 2020, 9(12): 2709.
5 Jiang X, Stockwell BR, Conrad M. Ferroptosis: mechanisms, biology and role in disease[J]. Nat Rev Mol Cell Biol, 2021, 22(4): 266-282.
6 Stites SW, Plautz MW, Bailey K, et al. Increased concentrations of iron and isoferritins in the lower respiratory tract of patients with stable cystic fibrosis[J]. Am J Respir Crit Care Med, 1999, 160(3): 796-801.
7 Ghio AJ, Carter JD, Richards JH, et al. Iron and iron-related proteins in the lower respiratory tract of patients with acute respiratory distress syndrome[J]. Crit Care Med, 2003, 31(2): 395-400.
8 Schmidt R, Luboeinski T, Markart P, et al. Alveolar antioxidant status in patients with acute respiratory distress syndrome[J]. Eur Respir J, 2004, 24(6): 994-999.
9 Britt RJ, Velten M, Locy ML, et al. The thioredoxin reductase-1 inhibitor aurothioglucose attenuates lung injury and improves survival in a murine model of acute respiratory distress syndrome[J]. Antioxid Redox Signal, 2014, 20(17): 2681-2691.
10 Organization WH. WHO Guideline on the prevention of drowning through provision of day-care and basic swimming and water safety skills[M]. World Health Organization, 2021.
11 Organization WH. Drowning[Z]. World Health Organization, 2021.
12 Bierens JJ, Lunetta P, Tipton M, et al. Physiology Of Drowning: A Review[J]. Physiology(Bethesda), 2016, 31(2): 147-166.
13 Pearn J. Pathophysiology of drowning[J]. Med J Aust, 1985, 142(11): 586-588.
14 王 凡, 韩志海. 炎症介质在海水淹溺急性肺损伤发生机制中的作用[J]. 转化医学杂志, 2015(5): 311-315.
15 Stockwell BR, Friedmann AJ, Bayir H, et al. Ferroptosis: A regulated cell death nexus linking metabolism, redox biology, and disease[J]. Cell, 2017, 171(2): 273-285.
16 Ayala A, Munoz MF, Arguelles S. Lipid peroxidation: production, metabolism, and signaling mechanisms of malondialdehyde and 4-hydroxy-2-nonenal[J]. Oxid Med Cell Longev, 2014, 2014: 360438.
17 Doll S, Proneth B, Tyurina YY, et al. ACSL4 dictates ferroptosis sensitivity by shaping cellular lipid composition[J]. Nat Chem Biol, 2017, 13(1): 91-98.
18 Dong X, Li D, Fang Z, et al. Astaxanthin alleviates lipopolysaccharide-induced acute lung injury by suppressing ferroptosis[J]. Food Funct, 2023, 14(13): 6115-6127.
19 Liu P, Feng Y, Li H, et al. Ferrostatin-1 alleviates lipopolysaccharide-induced acute lung injury via inhibiting ferroptosis[J]. Cell Mol Biol Lett, 2020, 25: 10.
20 Yu JB, Shi J, Gong LR, et al. Role of Nrf2/ARE pathway in protective effect of electroacupuncture against endotoxic shock-induced acute lung injury in rabbits[J]. PLoS One, 2014, 9(8): e104924.
21 Li J, Cao F, Yin HL, et al. Ferroptosis: past, present and future[J]. Cell Death Dis, 2020, 11(2): 88.
22 Tonnus W, Linkermann A. The in vivo evidence for regulated necrosis[J]. Immunol Rev, 2017, 277(1): 128-149.
23 Dong H, Qiang Z, Chai D, et al. Nrf2 inhibits ferroptosis and protects against acute lung injury due to intestinal ischemia reperfusion via regulating SLC7A11 and HO-1[J]. Aging(Albany NY), 2020, 12(13): 12943-12959.
24 Zhou H, Li F, Niu JY, et al. Ferroptosis was involved in the oleic acid-induced acute lung injury in mice[J]. Sheng Li Xue Bao, 2019, 71(5): 689-697.
25 Qiu YB, Wan BB, Liu G, et al. Nrf2 protects against seawater drowning-induced acute lung injury via inhibiting ferroptosis[J]. Respir Res, 2020, 21(1): 232.
26 段 锐, 金发光. TGF-β1/Smad2信号通路参与海水淹溺肺损伤引起的细胞凋亡[J/CD]. 中华肺部疾病杂志(电子版), 2020, 13(2): 154-158.

备注/Memo

备注/Memo:
通信作者: 金发光, Email: jinfag@fmmu.edu.cn
更新日期/Last Update: 2023-12-20