Omega-3 Fatty Acids Upregulate SIRT1/3, Activate PGC-1α via Deacetylation, and Induce Nrf1 Production in 5/6 Nephrectomy Rat Model
Mitochondrial dysfunction contributes to the pathogenesis of kidney injury related with cardiovascular disease. Peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1α) protects renal tubular cells by upregulating nuclear factor erythroid 2-related factor 2 (Nrf2). AMP-activated...
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MDPI AG
2021-03-01
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| Series: | Marine Drugs |
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| author | Sung Hyun Son Su Mi Lee Mi Hwa Lee Young Ki Son Seong Eun Kim Won Suk An |
| author_facet | Sung Hyun Son Su Mi Lee Mi Hwa Lee Young Ki Son Seong Eun Kim Won Suk An |
| author_sort | Sung Hyun Son |
| collection | DOAJ |
| description | Mitochondrial dysfunction contributes to the pathogenesis of kidney injury related with cardiovascular disease. Peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1α) protects renal tubular cells by upregulating nuclear factor erythroid 2-related factor 2 (Nrf2). AMP-activated protein kinase (pAMPK)-mediated phosphorylation and sirtuin 1/3 (SIRT1/3)-mediated deacetylation are required for PGC-1α activation. In the present study, we aimed to investigate whether omega-3 fatty acids (FAs) regulate the expression of mediators of mitochondrial biogenesis in 5/6 nephrectomy (Nx) rats. Male Sprague-Dawley rats were assigned to the following groups: sham control, Nx, and Nx treated with omega-3 FA. The expression of PGC-1α, phosphorylated PGC-1α (pPGC-1α), acetylated PGC-1α, and factors related to mitochondrial biogenesis was examined through Western blot analysis. Compared to the control group, the expression of PGC-1α, pAMPK, SIRT1/3, Nrf1, mTOR, and Nrf2 was significantly downregulated, and that of Keap 1, acetylated PGC-1α, and FoxO1/3, was significantly upregulated in the Nx group. These changes in protein expression were rescued in the omega-3 FA group. However, the expression of pPGC-1α was similar among the three groups. Omega-3 FAs may involve mitochondrial biogenesis by upregulating Nrf1 and Nrf2. This protective mechanism might be attributed to the increased expression and deacetylation of PGC-1α, which was triggered by SIRT1/3. |
| first_indexed | 2024-03-10T12:53:39Z |
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| language | English |
| last_indexed | 2024-03-10T12:53:39Z |
| publishDate | 2021-03-01 |
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| series | Marine Drugs |
| spelling | doaj.art-d665e64d20b34c1fbebf99d67e7051692023-11-21T12:05:37ZengMDPI AGMarine Drugs1660-33972021-03-0119418210.3390/md19040182Omega-3 Fatty Acids Upregulate SIRT1/3, Activate PGC-1α via Deacetylation, and Induce Nrf1 Production in 5/6 Nephrectomy Rat ModelSung Hyun Son0Su Mi Lee1Mi Hwa Lee2Young Ki Son3Seong Eun Kim4Won Suk An5Department of Internal Medicine, BHS Han Seo Hospital, Busan 48253, KoreaDepartment of Internal Medicine, Dong-A University, Busan 49201, KoreaDepartment of Anatomy and Cell Biology, Dong-A University, Busan 49201, KoreaDepartment of Internal Medicine, Dong-A University, Busan 49201, KoreaDepartment of Internal Medicine, Dong-A University, Busan 49201, KoreaDepartment of Internal Medicine, Dong-A University, Busan 49201, KoreaMitochondrial dysfunction contributes to the pathogenesis of kidney injury related with cardiovascular disease. Peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1α) protects renal tubular cells by upregulating nuclear factor erythroid 2-related factor 2 (Nrf2). AMP-activated protein kinase (pAMPK)-mediated phosphorylation and sirtuin 1/3 (SIRT1/3)-mediated deacetylation are required for PGC-1α activation. In the present study, we aimed to investigate whether omega-3 fatty acids (FAs) regulate the expression of mediators of mitochondrial biogenesis in 5/6 nephrectomy (Nx) rats. Male Sprague-Dawley rats were assigned to the following groups: sham control, Nx, and Nx treated with omega-3 FA. The expression of PGC-1α, phosphorylated PGC-1α (pPGC-1α), acetylated PGC-1α, and factors related to mitochondrial biogenesis was examined through Western blot analysis. Compared to the control group, the expression of PGC-1α, pAMPK, SIRT1/3, Nrf1, mTOR, and Nrf2 was significantly downregulated, and that of Keap 1, acetylated PGC-1α, and FoxO1/3, was significantly upregulated in the Nx group. These changes in protein expression were rescued in the omega-3 FA group. However, the expression of pPGC-1α was similar among the three groups. Omega-3 FAs may involve mitochondrial biogenesis by upregulating Nrf1 and Nrf2. This protective mechanism might be attributed to the increased expression and deacetylation of PGC-1α, which was triggered by SIRT1/3.https://www.mdpi.com/1660-3397/19/4/182peroxisome proliferator-activated receptor gamma coactivator-1 alphanuclear respiratory factor 1nuclear factor erythroid 2-related factor 2sirtuin 1sirtuin 3omega-3 fatty acid |
| spellingShingle | Sung Hyun Son Su Mi Lee Mi Hwa Lee Young Ki Son Seong Eun Kim Won Suk An Omega-3 Fatty Acids Upregulate SIRT1/3, Activate PGC-1α via Deacetylation, and Induce Nrf1 Production in 5/6 Nephrectomy Rat Model Marine Drugs peroxisome proliferator-activated receptor gamma coactivator-1 alpha nuclear respiratory factor 1 nuclear factor erythroid 2-related factor 2 sirtuin 1 sirtuin 3 omega-3 fatty acid |
| title | Omega-3 Fatty Acids Upregulate SIRT1/3, Activate PGC-1α via Deacetylation, and Induce Nrf1 Production in 5/6 Nephrectomy Rat Model |
| title_full | Omega-3 Fatty Acids Upregulate SIRT1/3, Activate PGC-1α via Deacetylation, and Induce Nrf1 Production in 5/6 Nephrectomy Rat Model |
| title_fullStr | Omega-3 Fatty Acids Upregulate SIRT1/3, Activate PGC-1α via Deacetylation, and Induce Nrf1 Production in 5/6 Nephrectomy Rat Model |
| title_full_unstemmed | Omega-3 Fatty Acids Upregulate SIRT1/3, Activate PGC-1α via Deacetylation, and Induce Nrf1 Production in 5/6 Nephrectomy Rat Model |
| title_short | Omega-3 Fatty Acids Upregulate SIRT1/3, Activate PGC-1α via Deacetylation, and Induce Nrf1 Production in 5/6 Nephrectomy Rat Model |
| title_sort | omega 3 fatty acids upregulate sirt1 3 activate pgc 1α via deacetylation and induce nrf1 production in 5 6 nephrectomy rat model |
| topic | peroxisome proliferator-activated receptor gamma coactivator-1 alpha nuclear respiratory factor 1 nuclear factor erythroid 2-related factor 2 sirtuin 1 sirtuin 3 omega-3 fatty acid |
| url | https://www.mdpi.com/1660-3397/19/4/182 |
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