A549细胞氧糖剥夺/恢复模型中焦亡与凋亡的共享信号通路

安雨轩; 肖宗懿; 王小燕; 宋娟; 陈菲; 王寿勇

doi:10.16016/j.2097-0927.202112247

您当前的位置：

首页 >

文章列表页 >

A549细胞氧糖剥夺/恢复模型中焦亡与凋亡的共享信号通路

基础医学 | 更新时间：2026-01-09

- A549细胞氧糖剥夺/恢复模型中焦亡与凋亡的共享信号通路
- Shared signaling pathway in pyroptosis and apoptosis in A549 cells induced by oxygen and glucose deprivation/recovery
- 陆军军医大学学报 2022年44卷第11期页码：1119-1125
- 作者机构：
  
  400014 重庆，重庆医科大学附属儿童医院麻醉科，国家儿童健康与疾病临床医学研究中心，儿童发育疾病研究教育部重点实验室，儿科学重庆市重点实验室
- 作者简介：
  
  [王寿勇，E-mail: saulwang@126.comWANG Shouyong, E-mail: saulwang@126.com
- 基金信息：
  
  重庆市自然科学基金项目(cstc2020jcyj-msxmX0357)
- DOI：10.16016/j.2097-0927.202112247
  中图分类号： R322.35;R329.25;R329.26
- 收稿：2021-12-28，
  
  修回：2022-01-26，
  
  纸质出版：2022-06-15
- 稿件说明：
移动端阅览
安雨轩, 肖宗懿, 王小燕, 等. A549细胞氧糖剥夺/恢复模型中焦亡与凋亡的共享信号通路[J]. 陆军军医大学学报, 2022,44(11):1119-1125.

Yuxuan AN, Zongyi XIAO, Xiaoyan WANG, et al. Shared signaling pathway in pyroptosis and apoptosis in A549 cells induced by oxygen and glucose deprivation/recovery[J]. Journal of Army Medical University, 2022, 44(11): 1119-1125.
安雨轩, 肖宗懿, 王小燕, 等. A549细胞氧糖剥夺/恢复模型中焦亡与凋亡的共享信号通路[J]. 陆军军医大学学报, 2022,44(11):1119-1125. DOI： 10.16016/j.2097-0927.202112247.

Yuxuan AN, Zongyi XIAO, Xiaoyan WANG, et al. Shared signaling pathway in pyroptosis and apoptosis in A549 cells induced by oxygen and glucose deprivation/recovery[J]. Journal of Army Medical University, 2022, 44(11): 1119-1125. DOI： 10.16016/j.2097-0927.202112247.

摘要

目的

研究氧糖剥夺/恢复(oxygen-glucose deprivation/recovery

OGD/R)对A549肺泡上皮细胞凋亡与焦亡的作用，并探讨二者之间的相互影响。

方法

培养人肺泡A549细胞株，建立氧糖剥夺/恢复细胞损伤模型，分为对照组(control)，氧糖剥夺/恢复组(OGD/R)，氧糖剥夺/恢复复合焦亡抑制剂组(OGD/R+VX-765)，氧糖剥夺/恢复复合凋亡抑制剂组(OGD/R+FMK)，采用流式细胞术检测细胞凋亡率，采用ELISA法测定培养细胞上清中焦亡标志物IL-1β、IL-18水平，采用RT-qPCR和Western blot法测定细胞凋亡和焦亡关键分子的mRNA与蛋白质表达水平。

结果

与对照组比较，OGD/R组A549细胞凋亡率升高。与OGD/R组比较，OGD/R+VX-765组凋亡率降低；与对照组比较，OGD/R组培养上清中焦亡标志物IL-1β、IL-18水平升高[(7.80±0.80)ng/L、(7.99±0.11) ng/L与(17.35±0.44) n

g/L、(18.06±1.73) ng/L，

0.05

]

；与OGD/R组比较，OGD/R+FMK组IL-1β、IL-18水平降低；OGD/R可刺激A549细胞凋亡与焦亡关键分子的mRNA和蛋白表达；与OGD/R组比较，OGD/R+VX-765组BID的mRNA和蛋白相对表达量降低，OGD/R+FMK组GSDME的mRNA和蛋白相对表达量降低。

结论

OGD/R可同时引发A549细胞发生焦亡与凋亡，且细胞焦亡与凋亡存在共享信号通路；两种抑制剂均可同时抑制OGD/R引起的A549细胞焦亡与凋亡。

Abstract

Objective

To investigate the effects of oxygen and glucose deprivation/recovery (OGD/R) on apoptosis and pyroptosis of A549 cells

and to explore the possibility of the mutual regulation in apoptosis and pyroptosis.

Methods

A549 cells were resuscitated and cultured

randomly divided into control group

OGD/R group

OGD/R+pyroptosis inhibitor group (OGD/R+VX-765) and OGD/R+apoptosis inhibitor group (OGD/R+FMK). The apoptotic rate was detected by flow cytometry

the levels of pyroptosis markers IL-1β and IL-18 in the supernatant were measured by ELISA

and the expression of key molecules in pyroptosis and apoptosis at mRNA and protein levels were detected by RT-qPCR and Western blotting

respectively.

Results

The apoptotic rate was significantly increased in the OGD/R group than the control group (12.57±1.97

3.67±0.64

0.05)

and the rate of the OGD/R+VX-765 group was decreased than that of the OGD/R group (5.97±1.28

0.05). OGD/R resulted in obvious increased levels of IL-1β and IL-18 in the supernatant (17.35±0.44

7.80±0.80 ng/L

18.06±1.73

7.99±0.11 ng/L

0.05)

but FMK treatment notably reversed the increases of 2 inflammatory factors (4.72±0.59

10.24±1.42 ng/L

0.05). OGD/R enhanced the mRNA and protein expression levels of key molecules of apoptosis and proptosis in A549 cells. While

VX-765 decreased the mRNA and protein levels of BID (1.12±0.18

1.74±0.14

1.01±0.10

1.29±0.09

0.05)

and FMK reduced those of GSDME (0.94±0.05

1.35±0.10

0.52±0.03

1.20±0.06

0.05) when compared with the cells from the OGD/R group.

Conclusion

OGD/R can induce pyroptosis and apoptosis in A549 cells simultaneously

and there exists shared signaling pathway in pyroptosis and apoptosis. Pyroptosis and apoptosis inhibitors can simultaneously inhibit the 2 types of OGD/R-induced cell death.

关键词

Keywords

references

DENG Y X, HOU L, XU Q Y, et al . Cardiopulmonary bypass induces acute lung injury via the high-mobility group box 1/toll-like receptor 4 pathway[J ] . Dis Markers, 2020, 2020: 8854700. DOI:10.1155/2020/8854700.

KARACALILAR M, ONAN I S, ONAN B, et al . Effects of pulmonary perfusion during cardiopulmonary bypass on lung functions after cardiac operation[J ] . J Card Surg, 2020, 35(10): 2469-2476. DOI:10.1111/jocs.14934.

YUAN S M. Postperfusion lung syndrome: physiopathology and therapeutic options[J]. Rev Bras Cir Cardiovasc, 2014, 29(3): 414-425. DOI:10.5935/1678-9741.20140071.

HU Z Z, YUAN Y, ZHANG X L, et al . Human umbilical cord mesenchymal stem cell-derived exosomes attenuate oxygen-glucose deprivation/reperfusion-induced microglial pyroptosis by promoting FOXO3a-dependent mitophagy[J ] . Oxid Med Cell Longev, 2021, 2021: 6219715. DOI:10.1155/2021/6219715.

XIE P, REN Z K, LV J, et al . Berberine ameliorates oxygen-glucose deprivation/reperfusion-induced apoptosis by inhibiting endoplasmic Reticulum stress and autophagy in PC12 cells[J ] . Curr Med Sci, 2020, 40(6): 1047-1056. DOI:10.1007/s11596-020-2286-x.

SHI J J, GAO W Q, SHAO F. Pyroptosis: gasdermin-mediated programmed necrotic cell death[J]. Trends Biochem Sci, 2017, 42(4): 245-254. DOI:10.1016/j.tibs.2016.10.004.

WANG Q, WU J F, ZENG Y C, et al . Pyroptosis: a pro-inflammatory type of cell death in cardiovascular disease[J ] . Clin Chim Acta, 2020, 510: 62-72. DOI:10.1016/j.cca.2020.06.044.

MCKENZIE B A, DIXIT V M, POWER C. Fiery cell death: pyroptosis in the central nervous system[J]. Trends Neurosci, 2020, 43(1): 55-73. DOI:10.1016/j.tins.2019.11.005.

XU X B, LAI Y Y, HUA Z C. Apoptosis and apoptotic body: disease message and therapeutic target potentials[J]. Biosci Rep, 2019, 39(1): BSR20180992. DOI:10.1042/BSR20180992.

KACZANOWSKI S. Apoptosis: its origin, history, maintenance and the medical implications for cancer and aging[J]. Phys Biol, 2016, 13(3): 031001. DOI:10.1088/1478-3975/13/3/031001.

王小燕, 肖宗懿, 易寒, 等. 氧糖剥夺/恢复对A549肺泡上皮细胞焦亡的影响[J]. 中国细胞生物学学报, 2020, 42(11): 1969-1974.

WANG X Y, XIAO Z Y, YI H, et al . Effects of oxygen-glucose deprivation/recovery on pyroptosis of A549 alveolar epithelial cells[J ] . Chin J Cell Biol, 2020, 42(11): 1969-1974.

MAN S M, KARKI R, KANNEGANTI T D. Molecular mechanisms and functions of pyroptosis, inflammatory caspases and inflammasomes in infectious diseases[J]. Immunol Rev, 2017, 277(1): 61-75. DOI:10.1111/imr.12534.

MAHIB M R, HOSOJIMA S, KUSHIYAMA H, et al . Caspase-7 mediates caspase-1-induced apoptosis independently of bid[J ] . Microbiol Immunol, 2020, 64(2): 143-152. DOI:10.1111/1348-0421.12756.

RIGO A, FERRARINI I, LORENZETTO E, et al . BID and the α-bisabolol-triggered cell death program: converging on mitochondria and lysosomes[J ] . Cell Death Dis, 2019, 10(12): 889. DOI:10.1038/s41419-019-2126-8.

ORNING P, LIEN E, FITZGERALD K A. Gasdermins and their role in immunity and inflammation[J]. J Exp Med, 2019, 216(11): 2453-2465. DOI:10.1084/jem.20190545.

RUAN J W, WANG S J, WANG J B. Mechanism and regulation of pyroptosis-mediated in cancer cell death[J]. Chem Biol Interact, 2020, 323: 109052. DOI:10.1016/j.cbi.2020.109052.

WANG Y P, GAO W Q, SHI X Y, et al . Chemotherapy drugs induce pyroptosis through caspase-3 cleavage of a gasdermin[J ] . Nature, 2017, 547(7661): 99-103. DOI:10.1038/nature22393.

ALI A, CYPEL M. Commentary: To Die or not to Die-rescuing lung cells from ischemia-reperfusion injury[J]. J Thorac Cardiovasc Surg, 2022, 163(2): e123-e124. DOI:10.1016/j.jtcvs.2021.01.091.

LAGIER D, FISCHER F, FORNIER W, et al . Effect of open-lung vs conventional perioperative ventilation strategies on postoperative pulmonary complications after on-pump cardiac surgery: the PROVECS randomized clinical trial[J ] . Intens Care Med, 2019, 45(10): 1401-1412. DOI:10.1007/s00134-019-05741-8..

浏览量

下载量

CSCD

文章被引用时，请邮件提醒。

提交

工具集

关联资源

人脂肪干细胞外泌体对烟熏诱导小鼠炎症和肺部损伤的治疗作用

甲基莲心碱通过抑制ROS/NLRP3/Caspase-1通路减少小胶质细胞焦亡并改善帕金森病神经炎症

肉桂醛对糖尿病溃疡血管内皮细胞Bax/Bak和凋亡的影响

二氢杨梅素改善糖尿病肾病的关键靶分子的筛选与验证

下调HOXA-AS2/miR-20a通路促进皮肤鳞癌细胞凋亡并抑制其侵袭迁移