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Duck gasdermin E is a substrate of caspase-3/-7 and an executioner of pyroptosis

Gasdermin (GSDM)-mediated cell death is an ancient immune defensive mechanism that plays an essential role in bacteria, fungi, coral, teleost, and mammals. After being cleaved by proteases of hosts or pathogens, amino-terminal (NT) fragment of GSDMs (GSDM-NTs) form pores in the membrane structure of...

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Autores principales: Li, Hanqing, Wang, Xin, Yu, Lanjie, Wang, Junwei, Cao, Yongsheng, Ma, Bo, Zhang, Wenlong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9871645/
https://www.ncbi.nlm.nih.gov/pubmed/36703987
http://dx.doi.org/10.3389/fimmu.2022.1078526
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author Li, Hanqing
Wang, Xin
Yu, Lanjie
Wang, Junwei
Cao, Yongsheng
Ma, Bo
Zhang, Wenlong
author_facet Li, Hanqing
Wang, Xin
Yu, Lanjie
Wang, Junwei
Cao, Yongsheng
Ma, Bo
Zhang, Wenlong
author_sort Li, Hanqing
collection PubMed
description Gasdermin (GSDM)-mediated cell death is an ancient immune defensive mechanism that plays an essential role in bacteria, fungi, coral, teleost, and mammals. After being cleaved by proteases of hosts or pathogens, amino-terminal (NT) fragment of GSDMs (GSDM-NTs) form pores in the membrane structure of cells, thereby leading to pyroptotic cell death. However, the expression profile, activation mechanism and function of avian GSDMs have not been studied in depth yet. In the current study, genes encoding duck gasdermin E (duGSDME), caspase-3 (ducaspase-3) and ducaspase-7 were cloned from mRNA of a virus-challenged duck embryo. The cleavage of duGSDME by ducaspase-3/-7 was verified in the cell-free system and/or in human embryonic kidney cells (HEK293). Ducaspase-3/-7 could recognize and cleave duGSDME at 270DAVD273. Overexpression of duGSDME-NT (1-273aa) fragment led to pyroptosis-like morphological change, increased lactic dehydrogenase (LDH) release and propidium iodide uptake of HEK293 cells, which indicated that duGSDME-NTs could cause cell membrane damage. In addition, recombinantly expressed duGSDME-NT showed bactericidal activity to an enterotoxic Escherichia coli (F5+) strain. The expression level of duGSDME was low in duckling tissues. DHAV-3 challenge upregulated the expression of duGSDME and ducaspase-3 in different tissues and led to the activation of ducaspase-3 and cleavage of duGSDME. The results indicated that duGSDME is a substrate of ducapsase-3/-7, and duGSDME-NT can cause pyroptosis. In addition, duGSDME may play a role in the immune defense of ducks against infectious diseases after being cleaved by ducaspase-3. The current study provides essential information for further investigation of the mechanisms of avian innate immunity and avian diseases.
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spelling pubmed-98716452023-01-25 Duck gasdermin E is a substrate of caspase-3/-7 and an executioner of pyroptosis Li, Hanqing Wang, Xin Yu, Lanjie Wang, Junwei Cao, Yongsheng Ma, Bo Zhang, Wenlong Front Immunol Immunology Gasdermin (GSDM)-mediated cell death is an ancient immune defensive mechanism that plays an essential role in bacteria, fungi, coral, teleost, and mammals. After being cleaved by proteases of hosts or pathogens, amino-terminal (NT) fragment of GSDMs (GSDM-NTs) form pores in the membrane structure of cells, thereby leading to pyroptotic cell death. However, the expression profile, activation mechanism and function of avian GSDMs have not been studied in depth yet. In the current study, genes encoding duck gasdermin E (duGSDME), caspase-3 (ducaspase-3) and ducaspase-7 were cloned from mRNA of a virus-challenged duck embryo. The cleavage of duGSDME by ducaspase-3/-7 was verified in the cell-free system and/or in human embryonic kidney cells (HEK293). Ducaspase-3/-7 could recognize and cleave duGSDME at 270DAVD273. Overexpression of duGSDME-NT (1-273aa) fragment led to pyroptosis-like morphological change, increased lactic dehydrogenase (LDH) release and propidium iodide uptake of HEK293 cells, which indicated that duGSDME-NTs could cause cell membrane damage. In addition, recombinantly expressed duGSDME-NT showed bactericidal activity to an enterotoxic Escherichia coli (F5+) strain. The expression level of duGSDME was low in duckling tissues. DHAV-3 challenge upregulated the expression of duGSDME and ducaspase-3 in different tissues and led to the activation of ducaspase-3 and cleavage of duGSDME. The results indicated that duGSDME is a substrate of ducapsase-3/-7, and duGSDME-NT can cause pyroptosis. In addition, duGSDME may play a role in the immune defense of ducks against infectious diseases after being cleaved by ducaspase-3. The current study provides essential information for further investigation of the mechanisms of avian innate immunity and avian diseases. Frontiers Media S.A. 2023-01-10 /pmc/articles/PMC9871645/ /pubmed/36703987 http://dx.doi.org/10.3389/fimmu.2022.1078526 Text en Copyright © 2023 Li, Wang, Yu, Wang, Cao, Ma and Zhang https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original authors(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Immunology
Li, Hanqing
Wang, Xin
Yu, Lanjie
Wang, Junwei
Cao, Yongsheng
Ma, Bo
Zhang, Wenlong
Duck gasdermin E is a substrate of caspase-3/-7 and an executioner of pyroptosis
title Duck gasdermin E is a substrate of caspase-3/-7 and an executioner of pyroptosis
title_full Duck gasdermin E is a substrate of caspase-3/-7 and an executioner of pyroptosis
title_fullStr Duck gasdermin E is a substrate of caspase-3/-7 and an executioner of pyroptosis
title_full_unstemmed Duck gasdermin E is a substrate of caspase-3/-7 and an executioner of pyroptosis
title_short Duck gasdermin E is a substrate of caspase-3/-7 and an executioner of pyroptosis
title_sort duck gasdermin e is a substrate of caspase-3/-7 and an executioner of pyroptosis
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9871645/
https://www.ncbi.nlm.nih.gov/pubmed/36703987
http://dx.doi.org/10.3389/fimmu.2022.1078526
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