Shared signaling pathway in pyroptosis and apoptosis in A549 cells induced by oxygen and glucose deprivation/recovery

Yuxuan AN; Zongyi XIAO; Xiaoyan WANG; Juan SONG; Fei CHEN; Shouyong WANG

doi:10.16016/j.2097-0927.202112247

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Shared signaling pathway in pyroptosis and apoptosis in A549 cells induced by oxygen and glucose deprivation/recovery

Basic Medicine | 更新时间：2026-01-09

- Shared signaling pathway in pyroptosis and apoptosis in A549 cells induced by oxygen and glucose deprivation/recovery
- Journal of Army Medical University Vol. 44, Issue 11, Pages: 1119-1125(2022)
- 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：
- 基金信息：
  
  the Natural Science Foundation of Chongqing(cstc2020jcyj-msxmX0357)
- DOI：10.16016/j.2097-0927.202112247
  CLC： R322.35;R329.25;R329.26
- Received：28 December 2021，
  
  Revised：2022-01-26，
  
  Published：15 June 2022
- 稿件说明：
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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：

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

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