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Panoptosis Targets the Mechanism of PRDX1 Involvement in Acute Myocardial Infarction via ZBP1
Yu Sun1, Chengcheng Ji2, Yuanmei Zhang3
1Department of Cardiac Intensive Care Unit, the Cardiovascular Hospital, the Affiliated Guangdong Second Provincial General Hospital of Jinan University, Guangzhou, Guangdong, China.
Abstract:
PANoptosis is involved in various pathological processes, but its role in acute myocardial infarction (AMI) remains unclear. This study aimed to explore the mechanism by which PANoptosis is involved in AMI. GSE172270 was used as an internal test set, and GSE159657 served as an external validation set to identify disease targets for AMI. WGCNA was performed to identify potential hub genes associated with AMI. Then, genes related to PANoptosis among the disease targets of AMI were screened. Additionally, human cardiomyocytes AC16 and mouse cardiomyocytes HL-1 were cultured in sugar-free and serum-free medium for 4 h and 12 h, and the expression of key genes regulating PANoptosis was detected by qRT-PCR. Finally, mRNA interference and overexpression experiments were conducted to verify the expression of key mRNAs. A total of 45 upregulated and 125 downregulated differentially expressed genes (DEGs) were identified in the GSE172270 data set. WGCNA identified 891 potential hub genes associated with AMI. In the GSE159657 data set, 695 upregulated and 552 downregulated DEGs were identified. Four genes related to AMI-PANoptosis (PRDX1, MMACHC, BLVRB, and TXNL1) were screened. Through qRT-PCR verification, PRDX1 was identified as the most specific and significant gene. The expression of the PANoptosis positive regulator ZPB1 was upregulated, while the PANoptosis negative regulator TAK1 was downregulated. Additionally, key cell death genes (MLKL, p-MLKL, Caspase-3, Caspase-7, and GSDMD) were upregulated in sugar-free and serum-free culture. However, PRDX1 interference reversed these effects. Our study demonstrated that PRDX1 is a key regulator of PANoptosis in AMI.
Insights
PANoptosis, a cell death pathway, plays a role in acute myocardial infarction (AMI). This study identifies PRDX1 as a key regulator of PANoptosis in AMI, offering new therapeutic targets.
Area of Science:
- Cellular Biology
- Pathology
- Molecular Medicine
Background:
- PANoptosis is implicated in various diseases, but its specific role in acute myocardial infarction (AMI) is not well understood.
- Understanding the molecular mechanisms of cell death in AMI is crucial for developing effective treatments.
Purpose of the Study:
- To investigate the involvement and mechanism of PANoptosis in acute myocardial infarction (AMI).
- To identify key regulatory genes of PANoptosis in the context of AMI.
Main Methods:
- Utilized gene expression datasets (GSE172270, GSE159657) for differential gene expression analysis and Weighted Gene Co-expression Network Analysis (WGCNA).
- Screened for PANoptosis-related genes among AMI disease targets.
- Employed cell culture models (AC16, HL-1) under stress conditions and utilized qRT-PCR, mRNA interference, and overexpression to validate gene expression and function.
Main Results:
- Identified differentially expressed genes and 891 potential hub genes associated with AMI.
- Screened four key genes (PRDX1, MMACHC, BLVRB, TXNL1) involved in AMI-PANoptosis.
- PRDX1 was identified as the most significant gene, with its expression inversely correlating with PANoptosis markers (ZPB1, TAK1, MLKL, Caspase-3/7, GSDMD) in stressed cardiomyocytes.
Conclusions:
- PRDX1 acts as a critical regulator of PANoptosis in acute myocardial infarction.
- Targeting PRDX1 may offer a novel therapeutic strategy for managing AMI.
