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NQO1-induced activation of AMPK contributes to cancer cell death by oxygen-glucose deprivation
Oxygen and glucose deprivation (OGD) due to insufficient blood circulation can decrease cancer cell survival and proliferation in solid tumors. OGD increases the intracellular [AMP]/[ATP] ratio, thereby activating the AMPK. In this study, we have investigated the involvement of NQO1 in OGD-mediated...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4293602/ https://www.ncbi.nlm.nih.gov/pubmed/25586669 http://dx.doi.org/10.1038/srep07769 |
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author | Lee, Hyemi Oh, Eun-Taex Choi, Bo-Hwa Park, Moon-Taek Lee, Ja-Kyeong Lee, Jae-Seon Park, Heon Joo |
author_facet | Lee, Hyemi Oh, Eun-Taex Choi, Bo-Hwa Park, Moon-Taek Lee, Ja-Kyeong Lee, Jae-Seon Park, Heon Joo |
author_sort | Lee, Hyemi |
collection | PubMed |
description | Oxygen and glucose deprivation (OGD) due to insufficient blood circulation can decrease cancer cell survival and proliferation in solid tumors. OGD increases the intracellular [AMP]/[ATP] ratio, thereby activating the AMPK. In this study, we have investigated the involvement of NQO1 in OGD-mediated AMPK activation and cancer cell death. We found that OGD activates AMPK in an NQO1-dependent manner, suppressing the mTOR/S6K/4E-BP1 pathway, which is known to control cell survival. Thus, the depletion of NQO1 prevents AMPK-induced cancer cell death in OGD. When we blocked OGD-induced Ca(2+)/CaMKII signaling, the NQO1-induced activation of AMPK was attenuated. In addition, when we blocked the RyR signaling, the accumulation of intracellular Ca(2+) and subsequent activation of CaMKII/AMPK signaling was decreased in NQO1-expressing cells under OGD. Finally, siRNA-mediated knockdown of CD38 abrogated the OGD-induced activation of Ca(2+)/CaMKII/AMPK signaling. Taken together, we conclude that NQO1 plays a key role in the AMPK-induced cancer cell death in OGD through the CD38/cADPR/RyR/Ca(2+)/CaMKII signaling pathway. |
format | Online Article Text |
id | pubmed-4293602 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-42936022015-01-16 NQO1-induced activation of AMPK contributes to cancer cell death by oxygen-glucose deprivation Lee, Hyemi Oh, Eun-Taex Choi, Bo-Hwa Park, Moon-Taek Lee, Ja-Kyeong Lee, Jae-Seon Park, Heon Joo Sci Rep Article Oxygen and glucose deprivation (OGD) due to insufficient blood circulation can decrease cancer cell survival and proliferation in solid tumors. OGD increases the intracellular [AMP]/[ATP] ratio, thereby activating the AMPK. In this study, we have investigated the involvement of NQO1 in OGD-mediated AMPK activation and cancer cell death. We found that OGD activates AMPK in an NQO1-dependent manner, suppressing the mTOR/S6K/4E-BP1 pathway, which is known to control cell survival. Thus, the depletion of NQO1 prevents AMPK-induced cancer cell death in OGD. When we blocked OGD-induced Ca(2+)/CaMKII signaling, the NQO1-induced activation of AMPK was attenuated. In addition, when we blocked the RyR signaling, the accumulation of intracellular Ca(2+) and subsequent activation of CaMKII/AMPK signaling was decreased in NQO1-expressing cells under OGD. Finally, siRNA-mediated knockdown of CD38 abrogated the OGD-induced activation of Ca(2+)/CaMKII/AMPK signaling. Taken together, we conclude that NQO1 plays a key role in the AMPK-induced cancer cell death in OGD through the CD38/cADPR/RyR/Ca(2+)/CaMKII signaling pathway. Nature Publishing Group 2015-01-14 /pmc/articles/PMC4293602/ /pubmed/25586669 http://dx.doi.org/10.1038/srep07769 Text en Copyright © 2015, Macmillan Publishers Limited. All rights reserved http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder in order to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ |
spellingShingle | Article Lee, Hyemi Oh, Eun-Taex Choi, Bo-Hwa Park, Moon-Taek Lee, Ja-Kyeong Lee, Jae-Seon Park, Heon Joo NQO1-induced activation of AMPK contributes to cancer cell death by oxygen-glucose deprivation |
title | NQO1-induced activation of AMPK contributes to cancer cell death by oxygen-glucose deprivation |
title_full | NQO1-induced activation of AMPK contributes to cancer cell death by oxygen-glucose deprivation |
title_fullStr | NQO1-induced activation of AMPK contributes to cancer cell death by oxygen-glucose deprivation |
title_full_unstemmed | NQO1-induced activation of AMPK contributes to cancer cell death by oxygen-glucose deprivation |
title_short | NQO1-induced activation of AMPK contributes to cancer cell death by oxygen-glucose deprivation |
title_sort | nqo1-induced activation of ampk contributes to cancer cell death by oxygen-glucose deprivation |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4293602/ https://www.ncbi.nlm.nih.gov/pubmed/25586669 http://dx.doi.org/10.1038/srep07769 |
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