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Resveratrol protects mitochondrial quantity by activating SIRT1/PGC‐1α expression during ovarian hypoxia

PURPOSE: Resveratrol is a well‐known potent activator of sirtuin‐1 (SIRT1). We investigated the direct effects of hypoxia and resveratrol on SIRT1/ peroxisome proliferator‐activated receptor‐gamma coactivator 1α (PGC‐1α) pathways, vascular endothelial growth factor (VEGF), hypoxia‐inducible factor (...

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Autores principales: Nishigaki, Akemi, Kido, Takeharu, Kida, Naoko, Kakita‐Kobayashi, Maiko, Tsubokura, Hiroaki, Hisamatsu, Yoji, Okada, Hidetaka
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7138948/
https://www.ncbi.nlm.nih.gov/pubmed/32273826
http://dx.doi.org/10.1002/rmb2.12323
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author Nishigaki, Akemi
Kido, Takeharu
Kida, Naoko
Kakita‐Kobayashi, Maiko
Tsubokura, Hiroaki
Hisamatsu, Yoji
Okada, Hidetaka
author_facet Nishigaki, Akemi
Kido, Takeharu
Kida, Naoko
Kakita‐Kobayashi, Maiko
Tsubokura, Hiroaki
Hisamatsu, Yoji
Okada, Hidetaka
author_sort Nishigaki, Akemi
collection PubMed
description PURPOSE: Resveratrol is a well‐known potent activator of sirtuin‐1 (SIRT1). We investigated the direct effects of hypoxia and resveratrol on SIRT1/ peroxisome proliferator‐activated receptor‐gamma coactivator 1α (PGC‐1α) pathways, vascular endothelial growth factor (VEGF), hypoxia‐inducible factor (HIF)‐1α, and mitochondrial quantity in a steroidogenic human ovarian granulosa‐like tumor cell line (KGN) cells. METHODS: KGN cells were cultured with cobalt chloride (CoCl(2); a hypoxia‐mimicking agent) and/or resveratrol. The mRNA and protein levels, protein secretion, and intracellular localization were assessed by real‐time PCR, Western blot analysis, ELISA, and immunofluorescence staining, respectively. Mitochondrial quantity was measured based on the mitochondrial DNA (mtDNA) copy number. RESULTS: CoCl(2) simultaneously attenuated the levels of SIRT1 and mtDNA expression, and induced the levels of VEGF protein production. In contrast, resveratrol significantly increased the levels of SIRT1 and mtDNA copy number, but reduced VEGF production in normoxia. Resveratrol could recover CoCl(2)‐suppressed SIRT1 and mtDNA expression and antagonize CoCl(2)‐induced VEGF production. CoCl(2) treatment resulted in a downregulation of PGC‐1α expression, and this effect was recovered by resveratrol. Resveratrol significantly suppressed the production of the CoCl(2)‐induced HIF‐1α and VEGF proteins. CONCLUSION: These results suggest that resveratrol improves mitochondrial quantity by activating the SIRT1/PGC‐1α pathway and inhibits VEGF induction through HIF‐1α under hypoxic conditions.
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spelling pubmed-71389482020-04-09 Resveratrol protects mitochondrial quantity by activating SIRT1/PGC‐1α expression during ovarian hypoxia Nishigaki, Akemi Kido, Takeharu Kida, Naoko Kakita‐Kobayashi, Maiko Tsubokura, Hiroaki Hisamatsu, Yoji Okada, Hidetaka Reprod Med Biol Original Articles PURPOSE: Resveratrol is a well‐known potent activator of sirtuin‐1 (SIRT1). We investigated the direct effects of hypoxia and resveratrol on SIRT1/ peroxisome proliferator‐activated receptor‐gamma coactivator 1α (PGC‐1α) pathways, vascular endothelial growth factor (VEGF), hypoxia‐inducible factor (HIF)‐1α, and mitochondrial quantity in a steroidogenic human ovarian granulosa‐like tumor cell line (KGN) cells. METHODS: KGN cells were cultured with cobalt chloride (CoCl(2); a hypoxia‐mimicking agent) and/or resveratrol. The mRNA and protein levels, protein secretion, and intracellular localization were assessed by real‐time PCR, Western blot analysis, ELISA, and immunofluorescence staining, respectively. Mitochondrial quantity was measured based on the mitochondrial DNA (mtDNA) copy number. RESULTS: CoCl(2) simultaneously attenuated the levels of SIRT1 and mtDNA expression, and induced the levels of VEGF protein production. In contrast, resveratrol significantly increased the levels of SIRT1 and mtDNA copy number, but reduced VEGF production in normoxia. Resveratrol could recover CoCl(2)‐suppressed SIRT1 and mtDNA expression and antagonize CoCl(2)‐induced VEGF production. CoCl(2) treatment resulted in a downregulation of PGC‐1α expression, and this effect was recovered by resveratrol. Resveratrol significantly suppressed the production of the CoCl(2)‐induced HIF‐1α and VEGF proteins. CONCLUSION: These results suggest that resveratrol improves mitochondrial quantity by activating the SIRT1/PGC‐1α pathway and inhibits VEGF induction through HIF‐1α under hypoxic conditions. John Wiley and Sons Inc. 2020-03-16 /pmc/articles/PMC7138948/ /pubmed/32273826 http://dx.doi.org/10.1002/rmb2.12323 Text en © 2020 The Authors. Reproductive Medicine and Biology published by John Wiley & Sons Australia, Ltd on behalf of Japan Society for Reproductive Medicine. This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Original Articles
Nishigaki, Akemi
Kido, Takeharu
Kida, Naoko
Kakita‐Kobayashi, Maiko
Tsubokura, Hiroaki
Hisamatsu, Yoji
Okada, Hidetaka
Resveratrol protects mitochondrial quantity by activating SIRT1/PGC‐1α expression during ovarian hypoxia
title Resveratrol protects mitochondrial quantity by activating SIRT1/PGC‐1α expression during ovarian hypoxia
title_full Resveratrol protects mitochondrial quantity by activating SIRT1/PGC‐1α expression during ovarian hypoxia
title_fullStr Resveratrol protects mitochondrial quantity by activating SIRT1/PGC‐1α expression during ovarian hypoxia
title_full_unstemmed Resveratrol protects mitochondrial quantity by activating SIRT1/PGC‐1α expression during ovarian hypoxia
title_short Resveratrol protects mitochondrial quantity by activating SIRT1/PGC‐1α expression during ovarian hypoxia
title_sort resveratrol protects mitochondrial quantity by activating sirt1/pgc‐1α expression during ovarian hypoxia
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7138948/
https://www.ncbi.nlm.nih.gov/pubmed/32273826
http://dx.doi.org/10.1002/rmb2.12323
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