MDM2 regulates H 2O 2 induced alveolar type II epithelial cell injury through p53/Bcl-2/Bax axis
10.3760/cma.j.issn.1671-0282.2024.08.007
- VernacularTitle:MDM2通过p53/Bcl-2/Bax轴调控H 2O 2诱导的肺泡Ⅱ型上皮细胞损伤
- Author:
Jie ZHENG
1
;
Bowen CHEN
;
Hong MEI
;
Xinxin LIU
;
Zhenliang LIAO
;
Kun YU
;
Hong YU
;
Banghai FENG
;
Miao CHEN
;
Xiaoyun FU
;
Song QIN
Author Information
1. 遵义医科大学附属医院重症医学科,遵义 563000
- Keywords:
Apoptosis;
MDM2;
Hyperoxic acute lung injury;
p53
- From:
Chinese Journal of Emergency Medicine
2024;33(8):1110-1116
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To explore the function of MDM2 and its relationship with p53 at the cellular level during H 2O 2 induced oxidative damage. Methods:MLE-12 HALI cell models were established using 0.5 mmol/L H 2O 2, and were divided into three groups: normal control group, H 2O 2 injury group, H 2O 2+MDM2 overexpressed group, and H 2O 2+MDM2 shRNA group. Infection of MLE-12 cells with adenovirus vector overexpressing and silencing MDM2; Using immunoprecipitation (Co-IP) to analyze the interaction between MDM2 and p53; Western blotting was used to detect the protein expression levels of MDM2, p53, Bcl-2, Bax, and cleared caspase-3 after HALI modeling; Measure the apoptosis rate of cells in each group. Results:After transcriptome sequencing,the p53 signaling pathway closely related to HALI. Compared with the normal group, the expression of MDM2 in the H 2O 2 injury group was lower ( P<0.05); Compared with the H 2O 2 injury group, overexpression of MDM2 resulted in a decrease in the apoptosis rate of MLE-12 cells ( P<0.05), a decrease in the expression levels of p53, Bax, and cleared caspase-3 proteins, and an upregulation of MDM2 and Bcl-2 protein expression ( P<0.05). Compared with the H 2O 2 injury group, when MDM2 was silenced, the cell apoptosis rate increased ( P<0.05), and the expression levels of p53, Bax, and cleared caspase-3 proteins were upregulated, while the expression levels of MDM2 and Bcl-2 proteins decreased ( P<0.05). Co-IP experiments showed that MDM2 binds to p53 protein. Conclusions:MDM2 can exert a protective effect on HALI by inhibiting MLE-12 cell apoptosis through the p53/Bcl-2/Bax axis.