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Recognition of Cytosolic DNA Attenuates Glucose Metabolism and Induces AMPK Mediated Energy Stress Response

Both viral infection and DNA transfection expose single-stranded or double-stranded DNA to the cytoplasm of mammalian cells. Recognition of cytosolic DNA activates a series of cellular responses, including induction of pro-inflammatory genes such as type I interferon through the well-known cGAS-STIN...

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Autores principales: Zheng, Min, Xie, Linna, Liang, Yaoji, Wu, Suqin, Xu, Huijuan, Zhang, Yuedong, Liu, Hekun, Lin, Dexin, Han, Jiahuai, Lu, Kunping
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Ivyspring International Publisher 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4400389/
https://www.ncbi.nlm.nih.gov/pubmed/25892965
http://dx.doi.org/10.7150/ijbs.10945
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author Zheng, Min
Xie, Linna
Liang, Yaoji
Wu, Suqin
Xu, Huijuan
Zhang, Yuedong
Liu, Hekun
Lin, Dexin
Han, Jiahuai
Lu, Kunping
author_facet Zheng, Min
Xie, Linna
Liang, Yaoji
Wu, Suqin
Xu, Huijuan
Zhang, Yuedong
Liu, Hekun
Lin, Dexin
Han, Jiahuai
Lu, Kunping
author_sort Zheng, Min
collection PubMed
description Both viral infection and DNA transfection expose single-stranded or double-stranded DNA to the cytoplasm of mammalian cells. Recognition of cytosolic DNA activates a series of cellular responses, including induction of pro-inflammatory genes such as type I interferon through the well-known cGAS-STING pathway. Here we show for the first time that intracellular administration of either single or double stranded interferon stimulating DNA (ISD), but not poly(dA) suppresses cell growth in many different cell types. Suppression of cell growth by cytosolic DNA is cGAS/STING independent and associated with inhibition of glucose metabolism, ATP depletion and subsequent cellular energy stress responses including activation of AMPK and inactivation of mTORC1. Our results suggest that in concert with but independent of innate immune response, recognition of cytosolic DNA induced cellular energy stress potentially functions as a metabolic barrier to viral replication.
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spelling pubmed-44003892015-04-17 Recognition of Cytosolic DNA Attenuates Glucose Metabolism and Induces AMPK Mediated Energy Stress Response Zheng, Min Xie, Linna Liang, Yaoji Wu, Suqin Xu, Huijuan Zhang, Yuedong Liu, Hekun Lin, Dexin Han, Jiahuai Lu, Kunping Int J Biol Sci Research Paper Both viral infection and DNA transfection expose single-stranded or double-stranded DNA to the cytoplasm of mammalian cells. Recognition of cytosolic DNA activates a series of cellular responses, including induction of pro-inflammatory genes such as type I interferon through the well-known cGAS-STING pathway. Here we show for the first time that intracellular administration of either single or double stranded interferon stimulating DNA (ISD), but not poly(dA) suppresses cell growth in many different cell types. Suppression of cell growth by cytosolic DNA is cGAS/STING independent and associated with inhibition of glucose metabolism, ATP depletion and subsequent cellular energy stress responses including activation of AMPK and inactivation of mTORC1. Our results suggest that in concert with but independent of innate immune response, recognition of cytosolic DNA induced cellular energy stress potentially functions as a metabolic barrier to viral replication. Ivyspring International Publisher 2015-04-05 /pmc/articles/PMC4400389/ /pubmed/25892965 http://dx.doi.org/10.7150/ijbs.10945 Text en © 2015 Ivyspring International Publisher. Reproduction is permitted for personal, noncommercial use, provided that the article is in whole, unmodified, and properly cited. See http://ivyspring.com/terms for terms and conditions.
spellingShingle Research Paper
Zheng, Min
Xie, Linna
Liang, Yaoji
Wu, Suqin
Xu, Huijuan
Zhang, Yuedong
Liu, Hekun
Lin, Dexin
Han, Jiahuai
Lu, Kunping
Recognition of Cytosolic DNA Attenuates Glucose Metabolism and Induces AMPK Mediated Energy Stress Response
title Recognition of Cytosolic DNA Attenuates Glucose Metabolism and Induces AMPK Mediated Energy Stress Response
title_full Recognition of Cytosolic DNA Attenuates Glucose Metabolism and Induces AMPK Mediated Energy Stress Response
title_fullStr Recognition of Cytosolic DNA Attenuates Glucose Metabolism and Induces AMPK Mediated Energy Stress Response
title_full_unstemmed Recognition of Cytosolic DNA Attenuates Glucose Metabolism and Induces AMPK Mediated Energy Stress Response
title_short Recognition of Cytosolic DNA Attenuates Glucose Metabolism and Induces AMPK Mediated Energy Stress Response
title_sort recognition of cytosolic dna attenuates glucose metabolism and induces ampk mediated energy stress response
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4400389/
https://www.ncbi.nlm.nih.gov/pubmed/25892965
http://dx.doi.org/10.7150/ijbs.10945
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