2. Academic Validation
  3. Paralichthys olivaceus GSDME-mediated pyroptosis is regulated by multiple caspases in different manners

Paralichthys olivaceus GSDME-mediated pyroptosis is regulated by multiple caspases in different manners

  • Fish Shellfish Immunol. 2024 Dec:155:110002. doi: 10.1016/j.fsi.2024.110002.
Kangwei Hao 1,  Liming Yuan 2,  Chao Yu 2,  Hang Xu 3,  Li Sun 4
Affiliations

Affiliations

  • 1 CAS and Shandong Province Key Laboratory of Experimental Marine Biology, Institute of Oceanology, Center for Ocean Mega-Science, Chinese Academy of Sciences, Qingdao, China; Laboratory for Marine Biology and Biotechnology, Qingdao Marine Science and Technology Center, Qingdao, China; College of Marine Sciences, University of Chinese Academy of Sciences, Qingdao, China.
  • 2 CAS and Shandong Province Key Laboratory of Experimental Marine Biology, Institute of Oceanology, Center for Ocean Mega-Science, Chinese Academy of Sciences, Qingdao, China.
  • 3 CAS and Shandong Province Key Laboratory of Experimental Marine Biology, Institute of Oceanology, Center for Ocean Mega-Science, Chinese Academy of Sciences, Qingdao, China; Laboratory for Marine Biology and Biotechnology, Qingdao Marine Science and Technology Center, Qingdao, China. Electronic address: xuhang@qdio.ac.cn.
  • 4 CAS and Shandong Province Key Laboratory of Experimental Marine Biology, Institute of Oceanology, Center for Ocean Mega-Science, Chinese Academy of Sciences, Qingdao, China; Laboratory for Marine Biology and Biotechnology, Qingdao Marine Science and Technology Center, Qingdao, China; College of Marine Sciences, University of Chinese Academy of Sciences, Qingdao, China. Electronic address: lsun@qdio.ac.cn.
PMID: 39491658 DOI: 10.1016/j.fsi.2024.110002
Abstract

Pyroptosis is a type of programmed cell death mediated by gasdermin (GSDM). GSDM is activated by Caspase (CASP), which cleaves GSDM to release the N-terminal (NT) fragment that forms channels in the plasma membrane and leads to cell death. To date, research on Pyroptosis in teleost is limited. In this study, we examined the activation and regulation mechanism of Pyroptosis in flounder Paralichthys olivaceus. P. olivaceus gasdermin E (PoGSDME) was found to be cleaved by six P. olivaceus caspases (PoCASP1/3a/3b/7/8a/8b). PoCASP1/3a/3b/7 cleaved primarily at 245FEAD248, which generated an NT fragment (NT248) that induced robust Pyroptosis. PoCASP8a/8b cleaved both the full length PoGSDME and NT248 at 202IEKD205, thus destroying the biological activity of PoGSDME and NT248. Nine residues crucial for PoGSDME function were identified, of which, F2, L19, and G85 were essential to plasma membrane translocation. During Bacterial infection, PoGSDME and PoCASP1 expressions were significantly upregulated in flounder tissues, and PoGSDME, as well as PoCASP1, activation occurred in flounder cells accompanied with the processing cleavage of IL-1β and IL-18. Together these results revealed both the activation and the inhibition mechanisms of GSDME-mediated Pyroptosis in flounder, and added new insights into the regulation of Pyroptosis in fish.

Keywords

Caspase; Gasdermin; Paralichthys olivaceus; Teleost.

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