Effects of acute hypoxia exposure with different durations on activation of Nrf2-ARE pathway in mouse skeletal muscle
Article
Article Title | Effects of acute hypoxia exposure with different durations on activation of Nrf2-ARE pathway in mouse skeletal muscle |
---|---|
ERA Journal ID | 39745 |
Article Category | Article |
Authors | Ji, Weixiu (Author), Wang, Linjia (Author), He, Shiyi (Author), Yan, Lu (Author), Li, Tieying (Author), Wang, Jianxiong (Author), Kong, Ah-Ng Tony (Author), Yu, Siwang (Author) and Zhang, Ying (Author) |
Journal Title | PLoS One |
Journal Citation | 13 (12), pp. 1-15 |
Number of Pages | 0 |
Year | 2018 |
Publisher | Public Library of Science (PLoS) |
Place of Publication | United States |
ISSN | 1932-6203 |
Digital Object Identifier (DOI) | https://doi.org/10.1371/journal.pone.0208474 |
Web Address (URL) | https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0208474 |
Abstract | Background Hypoxia training enhances the endurance capacity of athletes. This response may in part be attributed to the hypoxia-induced increase in antioxidant capacity in skeletal muscles. Nuclear factor erythroid 2-related factor 2 (Nrf2), a key transcription factor which regulates the expression of genes via binding to the antioxidant-response element (ARE) of these genes, plays a crucial role in stimulating the body’s defense system and potentially responds to hypoxia. Meanwhile, hypoxia-inducible factor-1α (HIF-1α) is an important player in protecting cells from hypoxic stress. The purpose of this study was to investigate the effects of acute hypoxia exposure with different durations on the activation of Nrf2-ARE pathway and a possible regulatory role of HIF-1α in these responses. Methods C57BL/6J mice were allocated into the non-hypoxia 0-hour, 6-hour, 24-hour, and 48-hour hypoxic exposure (11.2% oxygen) groups. The quadriceps femoris was collected immediately after hypoxia. Further, to investigate the possible role of HIF-1α, C2C12 myoblasts with HIF-1α knockdown by small interfering RNA (siRNA) and the inducible HIF-1α transgenic mice were employed. Results The results showed that 48-hour hypoxia exposure up-regulated protein expression of Nrf2, Nrf2/ARE binding activity and the transcription of antioxidative genes containing ARE (Sod1 and others) in mouse skeletal muscle. Moreover, HIF-1α siRNA group of C2C12 myoblasts showed a remarkable inhibition of Nrf2 protein expression and nuclear accumulation in hypoxia exposure for 72 hours compared with that in siRNA-Control group of the cells. In addition, HIF-1α transgenic mice gave higher Nrf2 protein expression, Nrf2/ARE binding activity and expressions of Nrf2-mediated antioxidative genes in their skeletal muscle, compared with those in the wild-type mice. Conclusions The findings suggested that the acute hypoxia exposure could trigger the activation of Nrf2-ARE pathway, with longer duration associated with higher responses, and HIF-1α expression might be involved in promoting the Nrf2-mediated antioxidant responses in skeletal muscle. © 2018 Ji et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
Keywords | hypoxia inducible factor 1alpha; small interfering RNA; transcription factor Nrf2; animal cell; antioxidant responsive element; binding affinity; C2C12 cell line; controlled study; disease duration; exposure; gene; gene activation; gene knockdown; hypoxia; male; mouse; nonhuman; protein expression; quadriceps femoris musc le; signal transduction; skeletal muscle; transgenic mouse; upregulation |
ANZSRC Field of Research 2020 | 310103. Cell metabolism |
420702. Exercise physiology | |
Public Notes | 'Copyright: ©2018 Ji et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited' - Publisher. |
Byline Affiliations | Beijing Sport University, China |
Faculty of Health, Engineering and Sciences | |
Rutgers University, United States | |
Peking University, China | |
Institution of Origin | University of Southern Queensland |
https://research.usq.edu.au/item/q4z8w/effects-of-acute-hypoxia-exposure-with-different-durations-on-activation-of-nrf2-are-pathway-in-mouse-skeletal-muscle
Download files
226
total views110
total downloads0
views this month0
downloads this month