Resveratrol protects mitochondrial quantity by activating SIRT1/PGC‐1α expression during ovarian hypoxia
Abstract 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...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2020-04-01
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| Series: | Reproductive Medicine and Biology |
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| Online Access: | https://doi.org/10.1002/rmb2.12323 |
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| author | Akemi Nishigaki Takeharu Kido Naoko Kida Maiko Kakita‐Kobayashi Hiroaki Tsubokura Yoji Hisamatsu Hidetaka Okada |
| author_facet | Akemi Nishigaki Takeharu Kido Naoko Kida Maiko Kakita‐Kobayashi Hiroaki Tsubokura Yoji Hisamatsu Hidetaka Okada |
| author_sort | Akemi Nishigaki |
| collection | DOAJ |
| description | Abstract 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 (CoCl2; 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 CoCl2 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 CoCl2‐suppressed SIRT1 and mtDNA expression and antagonize CoCl2‐induced VEGF production. CoCl2 treatment resulted in a downregulation of PGC‐1α expression, and this effect was recovered by resveratrol. Resveratrol significantly suppressed the production of the CoCl2‐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. |
| first_indexed | 2024-12-14T04:32:45Z |
| format | Article |
| id | doaj.art-db9fb0051ebf440b86bcfc05d0033395 |
| institution | Directory Open Access Journal |
| issn | 1445-5781 1447-0578 |
| language | English |
| last_indexed | 2024-12-14T04:32:45Z |
| publishDate | 2020-04-01 |
| publisher | Wiley |
| record_format | Article |
| series | Reproductive Medicine and Biology |
| spelling | doaj.art-db9fb0051ebf440b86bcfc05d00333952022-12-21T23:17:02ZengWileyReproductive Medicine and Biology1445-57811447-05782020-04-0119218919710.1002/rmb2.12323Resveratrol protects mitochondrial quantity by activating SIRT1/PGC‐1α expression during ovarian hypoxiaAkemi Nishigaki0Takeharu Kido1Naoko Kida2Maiko Kakita‐Kobayashi3Hiroaki Tsubokura4Yoji Hisamatsu5Hidetaka Okada6Department of Obstetrics and Gynecology Kansai Medical University Osaka JapanDepartment of Obstetrics and Gynecology Kansai Medical University Osaka JapanDepartment of Obstetrics and Gynecology Kansai Medical University Osaka JapanDepartment of Obstetrics and Gynecology Kansai Medical University Osaka JapanDepartment of Obstetrics and Gynecology Kansai Medical University Osaka JapanDepartment of Obstetrics and Gynecology Kansai Medical University Osaka JapanDepartment of Obstetrics and Gynecology Kansai Medical University Osaka JapanAbstract 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 (CoCl2; 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 CoCl2 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 CoCl2‐suppressed SIRT1 and mtDNA expression and antagonize CoCl2‐induced VEGF production. CoCl2 treatment resulted in a downregulation of PGC‐1α expression, and this effect was recovered by resveratrol. Resveratrol significantly suppressed the production of the CoCl2‐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.https://doi.org/10.1002/rmb2.12323hypoxia‐inducible factor‐1αmitochondrial DNA copy numberPGC‐1αresveratrolsirtuin‐1 |
| spellingShingle | Akemi Nishigaki Takeharu Kido Naoko Kida Maiko Kakita‐Kobayashi Hiroaki Tsubokura Yoji Hisamatsu Hidetaka Okada Resveratrol protects mitochondrial quantity by activating SIRT1/PGC‐1α expression during ovarian hypoxia Reproductive Medicine and Biology hypoxia‐inducible factor‐1α mitochondrial DNA copy number PGC‐1α resveratrol sirtuin‐1 |
| 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 | hypoxia‐inducible factor‐1α mitochondrial DNA copy number PGC‐1α resveratrol sirtuin‐1 |
| url | https://doi.org/10.1002/rmb2.12323 |
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