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Staphylococcus aureus-Induced Necroptosis Promotes Mitochondrial Damage in Goat Endometrial Epithelial Cells
SIMPLE SUMMARY: The death of endometrial cells induced by bacterial infections can result in damage to the endometrial function. In this study, we investigated the potential role of necroptosis in Staphylococcus aureus-induced goat endometrial epithelial cell (gEEC) death. We found that S. aureus in...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9454985/ https://www.ncbi.nlm.nih.gov/pubmed/36077938 http://dx.doi.org/10.3390/ani12172218 |
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author | Yi, Yanyan Gao, Kangkang Lin, Pengfei Chen, Huatao Zhou, Dong Tang, Keqiong Wang, Aihua Jin, Yaping |
author_facet | Yi, Yanyan Gao, Kangkang Lin, Pengfei Chen, Huatao Zhou, Dong Tang, Keqiong Wang, Aihua Jin, Yaping |
author_sort | Yi, Yanyan |
collection | PubMed |
description | SIMPLE SUMMARY: The death of endometrial cells induced by bacterial infections can result in damage to the endometrial function. In this study, we investigated the potential role of necroptosis in Staphylococcus aureus-induced goat endometrial epithelial cell (gEEC) death. We found that S. aureus induced gEECs RIPK1/RIPK3/MLKL-mediated necroptosis, triggered mainly by membrane disruption and ion imbalance. Moreover, gEEC necroptosis contributed to the regulation of reactive oxygen species generation and mitochondrial damage. These provide evidence of the involvement of necroptosis in the S. aureus-induced gEEC death. ABSTRACT: Endometrial cell death is induced by bacterial infection, resulting in damage to the physical barriers and immune function. An in-depth understanding of the mechanisms of endometrial epithelial cell necroptosis might provide new insights into the treatment of uterine diseases. In the present study, we investigated the effect of Staphylococcus aureus on goat endometrial epithelial cell (gEEC) necroptosis, and the underlying molecular mechanism. We found that S. aureus induced significant necroptosis in gEECs by increasing the expression of key proteins of the RIPK1/RIPK3/MLKL axis; importantly, this effect was alleviated by inhibitors of RIPK1, RIPK3, and MLKL. Moreover, we found that the main triggers of gEEC necroptosis induced by S. aureus were not the toll-like receptors (TLRs) and tumor necrosis factor receptor (TNFR), but membrane disruption and ion imbalance. Moreover, we observed a significant decrease in the mitochondrial membrane potential, indicating mitochondrial damage, in addition to increased cytochrome c levels and reactive oxygen species (ROS) generation in S. aureus-infected gEECs; these, effects were also suppressed by the inhibitors of RIPK1, RIPK3, and MLKL. Taken together, these data revealed the molecular mechanism of S. aureus-induced gEEC necroptosis and provided potential new targeted therapies for clinical intervention in bacterial infections. |
format | Online Article Text |
id | pubmed-9454985 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-94549852022-09-09 Staphylococcus aureus-Induced Necroptosis Promotes Mitochondrial Damage in Goat Endometrial Epithelial Cells Yi, Yanyan Gao, Kangkang Lin, Pengfei Chen, Huatao Zhou, Dong Tang, Keqiong Wang, Aihua Jin, Yaping Animals (Basel) Article SIMPLE SUMMARY: The death of endometrial cells induced by bacterial infections can result in damage to the endometrial function. In this study, we investigated the potential role of necroptosis in Staphylococcus aureus-induced goat endometrial epithelial cell (gEEC) death. We found that S. aureus induced gEECs RIPK1/RIPK3/MLKL-mediated necroptosis, triggered mainly by membrane disruption and ion imbalance. Moreover, gEEC necroptosis contributed to the regulation of reactive oxygen species generation and mitochondrial damage. These provide evidence of the involvement of necroptosis in the S. aureus-induced gEEC death. ABSTRACT: Endometrial cell death is induced by bacterial infection, resulting in damage to the physical barriers and immune function. An in-depth understanding of the mechanisms of endometrial epithelial cell necroptosis might provide new insights into the treatment of uterine diseases. In the present study, we investigated the effect of Staphylococcus aureus on goat endometrial epithelial cell (gEEC) necroptosis, and the underlying molecular mechanism. We found that S. aureus induced significant necroptosis in gEECs by increasing the expression of key proteins of the RIPK1/RIPK3/MLKL axis; importantly, this effect was alleviated by inhibitors of RIPK1, RIPK3, and MLKL. Moreover, we found that the main triggers of gEEC necroptosis induced by S. aureus were not the toll-like receptors (TLRs) and tumor necrosis factor receptor (TNFR), but membrane disruption and ion imbalance. Moreover, we observed a significant decrease in the mitochondrial membrane potential, indicating mitochondrial damage, in addition to increased cytochrome c levels and reactive oxygen species (ROS) generation in S. aureus-infected gEECs; these, effects were also suppressed by the inhibitors of RIPK1, RIPK3, and MLKL. Taken together, these data revealed the molecular mechanism of S. aureus-induced gEEC necroptosis and provided potential new targeted therapies for clinical intervention in bacterial infections. MDPI 2022-08-29 /pmc/articles/PMC9454985/ /pubmed/36077938 http://dx.doi.org/10.3390/ani12172218 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Yi, Yanyan Gao, Kangkang Lin, Pengfei Chen, Huatao Zhou, Dong Tang, Keqiong Wang, Aihua Jin, Yaping Staphylococcus aureus-Induced Necroptosis Promotes Mitochondrial Damage in Goat Endometrial Epithelial Cells |
title | Staphylococcus aureus-Induced Necroptosis Promotes Mitochondrial Damage in Goat Endometrial Epithelial Cells |
title_full | Staphylococcus aureus-Induced Necroptosis Promotes Mitochondrial Damage in Goat Endometrial Epithelial Cells |
title_fullStr | Staphylococcus aureus-Induced Necroptosis Promotes Mitochondrial Damage in Goat Endometrial Epithelial Cells |
title_full_unstemmed | Staphylococcus aureus-Induced Necroptosis Promotes Mitochondrial Damage in Goat Endometrial Epithelial Cells |
title_short | Staphylococcus aureus-Induced Necroptosis Promotes Mitochondrial Damage in Goat Endometrial Epithelial Cells |
title_sort | staphylococcus aureus-induced necroptosis promotes mitochondrial damage in goat endometrial epithelial cells |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9454985/ https://www.ncbi.nlm.nih.gov/pubmed/36077938 http://dx.doi.org/10.3390/ani12172218 |
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