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mTOR pathway mediates endoplasmic reticulum stress-induced CD4(+) T cell apoptosis in septic mice
Endoplasmic reticulum stress (ERS) has been well documented to participate in the pathophysiological processes of apoptosis in many diseases. Inhibition of ERS ameliorates pathological organ injury. However, the upstream signaling pathways and molecular regulatory mechanisms of which are still unkno...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Springer US
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9482898/ https://www.ncbi.nlm.nih.gov/pubmed/35759162 http://dx.doi.org/10.1007/s10495-022-01740-1 |
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author | Bai, Guangxu Wang, Hao Cui, Na |
author_facet | Bai, Guangxu Wang, Hao Cui, Na |
author_sort | Bai, Guangxu |
collection | PubMed |
description | Endoplasmic reticulum stress (ERS) has been well documented to participate in the pathophysiological processes of apoptosis in many diseases. Inhibition of ERS ameliorates pathological organ injury. However, the upstream signaling pathways and molecular regulatory mechanisms of which are still unknown. mTOR, an evolutionarily conserved protein kinase, is a key regulator of apoptosis. Hence, in this study, a classical cecal ligation and puncture (CLP) sepsis model was constructed by using the T cell-specific knockout mTOR and TSC1 (Tuberous Sclerosis Complex, the inhibitor of mTOR signaling pathway) mice to explore the underlying signaling pathway and molecular mechanism of host immune imbalance caused by apoptosis in sepsis. We found that mTOR may modulate septic T cell apoptosis by regulating Akt–IRE1–JNK pathway. To further clarify the possible mechanism, the specific inhibitors of PI3K-Akt and IRE1–JNK were used to intervene in mice before/after CLP, respectively. By analyzing the proteins of mTOR-ERS signaling pathway and the expression of apoptosis-related proteins and genes, we found that mTOR mediated the ER stress induced CD4(+) T cell apoptosis in Septic mice by negatively regulating the Akt–IRE1–JNK-Caspase 3 signaling cascades. These results indicate that mTOR–Akt–IRE1α–JNK signaling pathway mediated the Endoplasmic reticulum stress induced CD4(+) T cell apoptosis in Septic mice. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s10495-022-01740-1. |
format | Online Article Text |
id | pubmed-9482898 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Springer US |
record_format | MEDLINE/PubMed |
spelling | pubmed-94828982022-09-20 mTOR pathway mediates endoplasmic reticulum stress-induced CD4(+) T cell apoptosis in septic mice Bai, Guangxu Wang, Hao Cui, Na Apoptosis Article Endoplasmic reticulum stress (ERS) has been well documented to participate in the pathophysiological processes of apoptosis in many diseases. Inhibition of ERS ameliorates pathological organ injury. However, the upstream signaling pathways and molecular regulatory mechanisms of which are still unknown. mTOR, an evolutionarily conserved protein kinase, is a key regulator of apoptosis. Hence, in this study, a classical cecal ligation and puncture (CLP) sepsis model was constructed by using the T cell-specific knockout mTOR and TSC1 (Tuberous Sclerosis Complex, the inhibitor of mTOR signaling pathway) mice to explore the underlying signaling pathway and molecular mechanism of host immune imbalance caused by apoptosis in sepsis. We found that mTOR may modulate septic T cell apoptosis by regulating Akt–IRE1–JNK pathway. To further clarify the possible mechanism, the specific inhibitors of PI3K-Akt and IRE1–JNK were used to intervene in mice before/after CLP, respectively. By analyzing the proteins of mTOR-ERS signaling pathway and the expression of apoptosis-related proteins and genes, we found that mTOR mediated the ER stress induced CD4(+) T cell apoptosis in Septic mice by negatively regulating the Akt–IRE1–JNK-Caspase 3 signaling cascades. These results indicate that mTOR–Akt–IRE1α–JNK signaling pathway mediated the Endoplasmic reticulum stress induced CD4(+) T cell apoptosis in Septic mice. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s10495-022-01740-1. Springer US 2022-06-27 2022 /pmc/articles/PMC9482898/ /pubmed/35759162 http://dx.doi.org/10.1007/s10495-022-01740-1 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Article Bai, Guangxu Wang, Hao Cui, Na mTOR pathway mediates endoplasmic reticulum stress-induced CD4(+) T cell apoptosis in septic mice |
title | mTOR pathway mediates endoplasmic reticulum stress-induced CD4(+) T cell apoptosis in septic mice |
title_full | mTOR pathway mediates endoplasmic reticulum stress-induced CD4(+) T cell apoptosis in septic mice |
title_fullStr | mTOR pathway mediates endoplasmic reticulum stress-induced CD4(+) T cell apoptosis in septic mice |
title_full_unstemmed | mTOR pathway mediates endoplasmic reticulum stress-induced CD4(+) T cell apoptosis in septic mice |
title_short | mTOR pathway mediates endoplasmic reticulum stress-induced CD4(+) T cell apoptosis in septic mice |
title_sort | mtor pathway mediates endoplasmic reticulum stress-induced cd4(+) t cell apoptosis in septic mice |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9482898/ https://www.ncbi.nlm.nih.gov/pubmed/35759162 http://dx.doi.org/10.1007/s10495-022-01740-1 |
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