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Chenodeoxycholic Acid Reduces Hypoxia Inducible Factor-1α Protein and Its Target Genes
This study evaluated HIF-1α inhibitors under different hypoxic conditions, physiological hypoxia (5% O(2)) and severe hypoxia (0.1% O(2)). We found that chenodeoxy cholic acid (CDCA) reduced the amount of HIF-1α protein only under physiological hypoxia but not under severe hypoxia without decreasing...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4476666/ https://www.ncbi.nlm.nih.gov/pubmed/26098428 http://dx.doi.org/10.1371/journal.pone.0130911 |
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author | Moon, Yunwon Choi, Su Mi Chang, Soojeong Park, Bongju Lee, Seongyeol Lee, Mi-Ock Choi, Hueng-Sik Park, Hyunsung |
author_facet | Moon, Yunwon Choi, Su Mi Chang, Soojeong Park, Bongju Lee, Seongyeol Lee, Mi-Ock Choi, Hueng-Sik Park, Hyunsung |
author_sort | Moon, Yunwon |
collection | PubMed |
description | This study evaluated HIF-1α inhibitors under different hypoxic conditions, physiological hypoxia (5% O(2)) and severe hypoxia (0.1% O(2)). We found that chenodeoxy cholic acid (CDCA) reduced the amount of HIF-1α protein only under physiological hypoxia but not under severe hypoxia without decreasing its mRNA level. By using a proteasome inhibitor MG132 and a translation inhibitor cyclohexamide, we showed that CDCA reduced HIF-1α protein by decreasing its translation but not by enhancing its degradation. The following findings indicated that farnesoid X receptor (FXR), a CDCA receptor and its target gene, Small heterodimer partner (SHP) are not involved in this effect of CDCA. Distinctly from CDCA, MG132 prevented SHP and an exogenous FXR agonist, GW4064 from reducing HIF-1α protein. Furthermore a FXR antagonist, guggulsterone failed to prevent CDCA from decreasing HIF-1α protein. Furthermore, guggulsterone by itself reduced HIF-1α protein even in the presence of MG132. These findings suggested that CDCA and guggulsterone reduced the translation of HIF-1α in a mechanism which FXR and SHP are not involved. This study reveals novel therapeutic functions of traditional nontoxic drugs, CDCA and guggulsterone, as inhibitors of HIF-1α protein. |
format | Online Article Text |
id | pubmed-4476666 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-44766662015-06-25 Chenodeoxycholic Acid Reduces Hypoxia Inducible Factor-1α Protein and Its Target Genes Moon, Yunwon Choi, Su Mi Chang, Soojeong Park, Bongju Lee, Seongyeol Lee, Mi-Ock Choi, Hueng-Sik Park, Hyunsung PLoS One Research Article This study evaluated HIF-1α inhibitors under different hypoxic conditions, physiological hypoxia (5% O(2)) and severe hypoxia (0.1% O(2)). We found that chenodeoxy cholic acid (CDCA) reduced the amount of HIF-1α protein only under physiological hypoxia but not under severe hypoxia without decreasing its mRNA level. By using a proteasome inhibitor MG132 and a translation inhibitor cyclohexamide, we showed that CDCA reduced HIF-1α protein by decreasing its translation but not by enhancing its degradation. The following findings indicated that farnesoid X receptor (FXR), a CDCA receptor and its target gene, Small heterodimer partner (SHP) are not involved in this effect of CDCA. Distinctly from CDCA, MG132 prevented SHP and an exogenous FXR agonist, GW4064 from reducing HIF-1α protein. Furthermore a FXR antagonist, guggulsterone failed to prevent CDCA from decreasing HIF-1α protein. Furthermore, guggulsterone by itself reduced HIF-1α protein even in the presence of MG132. These findings suggested that CDCA and guggulsterone reduced the translation of HIF-1α in a mechanism which FXR and SHP are not involved. This study reveals novel therapeutic functions of traditional nontoxic drugs, CDCA and guggulsterone, as inhibitors of HIF-1α protein. Public Library of Science 2015-06-22 /pmc/articles/PMC4476666/ /pubmed/26098428 http://dx.doi.org/10.1371/journal.pone.0130911 Text en © 2015 Moon et al http://creativecommons.org/licenses/by/4.0/ 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 properly credited. |
spellingShingle | Research Article Moon, Yunwon Choi, Su Mi Chang, Soojeong Park, Bongju Lee, Seongyeol Lee, Mi-Ock Choi, Hueng-Sik Park, Hyunsung Chenodeoxycholic Acid Reduces Hypoxia Inducible Factor-1α Protein and Its Target Genes |
title | Chenodeoxycholic Acid Reduces Hypoxia Inducible Factor-1α Protein and Its Target Genes |
title_full | Chenodeoxycholic Acid Reduces Hypoxia Inducible Factor-1α Protein and Its Target Genes |
title_fullStr | Chenodeoxycholic Acid Reduces Hypoxia Inducible Factor-1α Protein and Its Target Genes |
title_full_unstemmed | Chenodeoxycholic Acid Reduces Hypoxia Inducible Factor-1α Protein and Its Target Genes |
title_short | Chenodeoxycholic Acid Reduces Hypoxia Inducible Factor-1α Protein and Its Target Genes |
title_sort | chenodeoxycholic acid reduces hypoxia inducible factor-1α protein and its target genes |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4476666/ https://www.ncbi.nlm.nih.gov/pubmed/26098428 http://dx.doi.org/10.1371/journal.pone.0130911 |
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