Ablation of Selenbp1 Alters Lipid Metabolism via the Pparα Pathway in Mouse Kidney
| Autor: | Takumi Ishida, Yingxia Song, Yoshitaka Tanaka, Yuko Onomura, Yuji Ishii, Takayuki Koga, Atsushi Kurose, Tomoki Takeda, Junpei Mutoh, Ren-Shi Li |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Male
kidney QH301-705.5 SOD1 SOD2 Peroxisome proliferator-activated receptor Gene Expression Selenium-Binding Proteins Catalysis Article Inorganic Chemistry Superoxide dismutase chemistry.chemical_compound Mice lipid metabolism Animals oxidative stress PPAR alpha RNA Messenger Physical and Theoretical Chemistry Biology (General) Molecular Biology QD1-999 Spectroscopy mouse chemistry.chemical_classification Retinoid X Receptor alpha Ppar biology Superoxide selenium binding protein 1 peroxisome proliferator-activated receptor-alpha Organic Chemistry Cytochrome P450 Lipid metabolism General Medicine Lipids Computer Science Applications Cell biology Mice Inbred C57BL Chemistry chemistry biology.protein Peroxisome proliferator-activated receptor alpha Cytochrome P-450 CYP4A Transcription Factors |
| Zdroj: | International Journal of Molecular Sciences Volume 22 Issue 10 International Journal of Molecular Sciences, Vol 22, Iss 5334, p 5334 (2021) |
| ISSN: | 1422-0067 |
| DOI: | 10.3390/ijms22105334 |
| Popis: | Selenium-binding protein 1 (Selenbp1) is a 2,3,7,8-tetrechlorodibenzo-p-dioxin inducible protein whose function is yet to be comprehensively elucidated. As the highly homologous isoform, Selenbp2, is expressed at low levels in the kidney, it is worthwhile comparing wild-type C57BL mice and Selenbp1-deficient mice under dioxin-free conditions. Accordingly, we conducted a mouse metabolomics analysis under non-dioxin-treated conditions. DNA microarray analysis was performed based on observed changes in lipid metabolism-related factors. The results showed fluctuations in the expression of numerous genes. Real-time RT-PCR confirmed the decreased expression levels of the cytochrome P450 4a (Cyp4a) subfamily, known to be involved in fatty acid ω- and ω-1 hydroxylation. Furthermore, peroxisome proliferator-activated receptor-α (Pparα) and retinoid-X-receptor-α (Rxrα), which form a heterodimer with Pparα to promote gene expression, were simultaneously reduced. This indicated that reduced Cyp4a expression was mediated via decreased Pparα and Rxrα. In line with this finding, increased levels of leukotrienes and prostaglandins were detected. Conversely, decreased hydrogen peroxide levels and reduced superoxide dismutase (SOD) activity supported the suppression of the renal expression of Sod1 and Sod2 in Selenbp1-deficient mice. Therefore, we infer that ablation of Selenbp1 elicits oxidative stress caused by increased levels of superoxide anions, which alters lipid metabolism via the Pparα pathway. |
| Databáze: | OpenAIRE |
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