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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...

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Autores principales: Bai, Guangxu, Wang, Hao, Cui, Na
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer US 2022
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.
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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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