|Table of Contents|

Role of GSDME in DADS-induced pyroptosis in leukemic K562 cells

Journal Of Modern Oncology[ISSN:1672-4992/CN:61-1415/R]

Issue:
2024 15
Page:
2730-2737
Research Field:
Publishing date:

Info

Title:
Role of GSDME in DADS-induced pyroptosis in leukemic K562 cells
Author(s):
ZHOU Lingyan; HU Xuanyuan; LIU Yinhua; YIN Xiaocheng
Department of Pediatrics,the First Affiliated Hospital of Hengyang Medical College,University of South China, Hunan Hengyang 421600,China.
Keywords:
DADS; K562; pyroptosis; GSDME
PACS:
R733.7
DOI:
10.3969/j.issn.1672-4992.2024.15.007
Abstract:
Objective:To investigate the molecular mechanisms of DADS-induced pyroptosis in K562 cells.Methods:We used Western Blot to detect the overall expression levels of GSDME and GSDMD proteins in Kasumi,K562,THP-1,HL-60,and NB4 cells.Methylation-specific PCR (MSP) was employed to assess the methylation status of the GSDME gene promoter region in K562 and NB4 cells.CCK-8 assays were conducted to evaluate the proliferative viability of K562 and NB4 cells after treatment with varying concentrations of DADS.Western Blot and LDH release experiments were utilized to measure changes in protein expression levels of GSDME,GSDME-N,IL-1β,Cleaved-IL-1β,as well as LDH release,in K562 cells following DADS treatment.Lentiviral transfection was utilized to establish stable cell lines with knockdown of GSDME in K562 cells.Western Blot was then performed to detect changes in the expression level of the GSDME-N terminal protein in the stable cell lines treated with DADS.Results:Significant differences in the expression levels of GSDME and GSDMD were observed among Kasumi,K562,THP-1,HL-60 and NB4 cells.MSP analysis positive bands for GSDME gene promoter methylation were detected in NB4 cells,while unmethylated amplification was negative.In K562 cells,unmethylated amplification was positive,but positive bands for GSDME gene promoter methylation was not detected.After DADS treatment the LDH release GSDME-N ,Cleaved-1L-1β protein of K562 cells were significantly increased (P<0.01).qRT-PCR and Western Blot knockdown of GSDME significantly reduced its mRNA and protein expression in K562 cells compared to NC groups (P<0.01).DADS treatment significantly increased GSDME-N protein levels in NC groups (P<0.001),and there was no significant difference in GSDME-N protein levels in the QD group after DADS treatment (P>0.05).The QD group showed a significant decrease in GSDME-N protein levels after DADS treatment compared to the NC-DADS group (P<0.001).Conclusion:DADS induces pyroptosis in K562 cells,and its molecular mechanism is related to the GSDME-mediated pyroptosis pathway.

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Memo

Memo:
National Natural Science Foundation of China（No.31271482）;国家自然科学基金面上项目（编号：31271482）；湖南省卫生健康委员会科技计划重点项目（编号：20201977）
Last Update: 2024-06-28