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A load of mice to hypergravity causes AMPKα repression with liver injury, which is overcome by preconditioning loads via Nrf2

An understanding of the effects of hypergravity on energy homeostasis is necessary in managing proper physiological countermeasures for aerospace missions. This study investigated whether a single or multiple load(s) of mice to hypergravity has an effect on molecules associated with energy metabolis...

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Autores principales: Lee, Sang Gil, Lee, Chan Gyu, Wu, Hong Min, Oh, Choong Sik, Chung, So Won, Kim, Sang Geon
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4616048/
https://www.ncbi.nlm.nih.gov/pubmed/26493041
http://dx.doi.org/10.1038/srep15643
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author Lee, Sang Gil
Lee, Chan Gyu
Wu, Hong Min
Oh, Choong Sik
Chung, So Won
Kim, Sang Geon
author_facet Lee, Sang Gil
Lee, Chan Gyu
Wu, Hong Min
Oh, Choong Sik
Chung, So Won
Kim, Sang Geon
author_sort Lee, Sang Gil
collection PubMed
description An understanding of the effects of hypergravity on energy homeostasis is necessary in managing proper physiological countermeasures for aerospace missions. This study investigated whether a single or multiple load(s) of mice to hypergravity has an effect on molecules associated with energy metabolism. In the liver, AMPKα level and its signaling were repressed 6 h after a load to +9 Gz hypergravity for 1 h, and then gradually returned toward normal. AMPKα level was restored after 3 loads to +9 Gz, suggestive of preconditioning adaptation. In cDNA microarray analyses, 221 genes were differentially expressed by +9 Gz, and the down-regulated genes included Nrf2 targets. Nrf2 gene knockout abrogated the recovery of AMPKα elicited by 3 loads to +9 Gz, indicating that Nrf2 plays a role in the adaptive increase of AMPKα. In addition, +9 Gz stress decreased STAT3, FOXO1/3 and CREB levels, which was attenuated during the resting time. Similarly, apoptotic markers were enhanced in the liver, indicating that the liver may be vulnerable to hypergravity stress. Preconditioning loads prevented hepatocyte apoptosis. Overall, a load of mice to +9 Gz hypergravity causes AMPKα repression with liver injury, which may be overcome by multiple loads to hypergravity as mediated by Nrf2.
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spelling pubmed-46160482015-10-29 A load of mice to hypergravity causes AMPKα repression with liver injury, which is overcome by preconditioning loads via Nrf2 Lee, Sang Gil Lee, Chan Gyu Wu, Hong Min Oh, Choong Sik Chung, So Won Kim, Sang Geon Sci Rep Article An understanding of the effects of hypergravity on energy homeostasis is necessary in managing proper physiological countermeasures for aerospace missions. This study investigated whether a single or multiple load(s) of mice to hypergravity has an effect on molecules associated with energy metabolism. In the liver, AMPKα level and its signaling were repressed 6 h after a load to +9 Gz hypergravity for 1 h, and then gradually returned toward normal. AMPKα level was restored after 3 loads to +9 Gz, suggestive of preconditioning adaptation. In cDNA microarray analyses, 221 genes were differentially expressed by +9 Gz, and the down-regulated genes included Nrf2 targets. Nrf2 gene knockout abrogated the recovery of AMPKα elicited by 3 loads to +9 Gz, indicating that Nrf2 plays a role in the adaptive increase of AMPKα. In addition, +9 Gz stress decreased STAT3, FOXO1/3 and CREB levels, which was attenuated during the resting time. Similarly, apoptotic markers were enhanced in the liver, indicating that the liver may be vulnerable to hypergravity stress. Preconditioning loads prevented hepatocyte apoptosis. Overall, a load of mice to +9 Gz hypergravity causes AMPKα repression with liver injury, which may be overcome by multiple loads to hypergravity as mediated by Nrf2. Nature Publishing Group 2015-10-23 /pmc/articles/PMC4616048/ /pubmed/26493041 http://dx.doi.org/10.1038/srep15643 Text en Copyright © 2015, Macmillan Publishers Limited 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 to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
spellingShingle Article
Lee, Sang Gil
Lee, Chan Gyu
Wu, Hong Min
Oh, Choong Sik
Chung, So Won
Kim, Sang Geon
A load of mice to hypergravity causes AMPKα repression with liver injury, which is overcome by preconditioning loads via Nrf2
title A load of mice to hypergravity causes AMPKα repression with liver injury, which is overcome by preconditioning loads via Nrf2
title_full A load of mice to hypergravity causes AMPKα repression with liver injury, which is overcome by preconditioning loads via Nrf2
title_fullStr A load of mice to hypergravity causes AMPKα repression with liver injury, which is overcome by preconditioning loads via Nrf2
title_full_unstemmed A load of mice to hypergravity causes AMPKα repression with liver injury, which is overcome by preconditioning loads via Nrf2
title_short A load of mice to hypergravity causes AMPKα repression with liver injury, which is overcome by preconditioning loads via Nrf2
title_sort load of mice to hypergravity causes ampkα repression with liver injury, which is overcome by preconditioning loads via nrf2
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4616048/
https://www.ncbi.nlm.nih.gov/pubmed/26493041
http://dx.doi.org/10.1038/srep15643
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