Ablation of Selenbp1 Alters Lipid Metabolism via the Pparα Pathway in Mouse Kidney
| Autor: | Yingxia Song, Atsushi Kurose, Renshi Li, Tomoki Takeda, Yuko Onomura, Takayuki Koga, Junpei Mutoh, Takumi Ishida, Yoshitaka Tanaka, Yuji Ishii |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: | |
| Zdroj: | International Journal of Molecular Sciences, Vol 22, Iss 10, p 5334 (2021) |
| Druh dokumentu: | article |
| ISSN: | 1422-0067 1661-6596 49563858 |
| 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: | Directory of Open Access Journals |
| Externí odkaz: |
|