Ischemia-reperfusion injury induces ZBP1-dependent PANoptosis in endothelial cells

IF 4.2 2区生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biochimica et biophysica acta. Molecular basis of disease Pub Date : 2025-03-06 DOI:10.1016/j.bbadis.2025.167782

Yue Cui , Huang Lin , Jiaxing Ma , Yinhua Zhao , Jiaxi Li , Yang Wang , Jingwei Zhuang , Yu Yang

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Abstract

Endothelial cells play a critical role in the pathophysiology of ischemia-reperfusion injury (IRI). Although previous studies have shown that IRI can activate PANoptosis, the underlying mechanisms remain unclear. Our research investigates how IRI induces PANoptosis in endothelial cells, aiming to identify protective strategies to safeguard these cells from PANoptosis triggered by IRI. We established an in vitro endothelial cell hypoxia/reoxygenation (H/R) treatment model and an in vivo SD rat free flap IRI model. A series of assays, including PI/Hoechst staining, Western blotting, and immunohistochemistry, were conducted to assess PANoptosis-like cell death in endothelial cells. Cell transfection with ZBP1 siRNA and immunoprecipitation were used to explore the involved signaling pathways. Our results showed activation of PANoptosis-like cell death and upregulation of ZBP1 expression following IRI. After knocking down ZBP1 expression, a significant alteration in PANoptosis-like cell death and the assembly of the ZBP1-PANoptosome in endothelial cells was observed, confirming the occurrence of PANoptosis. In conclusion, our research confirms that IRI induces PANoptosome formation, promoting ZBP1-dependent PANoptosis in endothelial cells.

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来源期刊

Biochimica et biophysica acta. Molecular basis of disease 生物-生化与分子生物学

CiteScore

12.30

自引率

0.00%

发文量

218

审稿时长

32 days

期刊介绍： BBA Molecular Basis of Disease addresses the biochemistry and molecular genetics of disease processes and models of human disease. This journal covers aspects of aging, cancer, metabolic-, neurological-, and immunological-based disease. Manuscripts focused on using animal models to elucidate biochemical and mechanistic insight in each of these conditions, are particularly encouraged. Manuscripts should emphasize the underlying mechanisms of disease pathways and provide novel contributions to the understanding and/or treatment of these disorders. Highly descriptive and method development submissions may be declined without full review. The submission of uninvited reviews to BBA - Molecular Basis of Disease is strongly discouraged, and any such uninvited review should be accompanied by a coverletter outlining the compelling reasons why the review should be considered.