| First Author | Tsushida K | Year | 2018 |
| Journal | Biochem Biophys Res Commun | Volume | 498 |
| Issue | 4 | Pages | 918-924 |
| PubMed ID | 29545177 | Mgi Jnum | J:273667 |
| Mgi Id | MGI:6277830 | Doi | 10.1016/j.bbrc.2018.03.080 |
| Citation | Tsushida K, et al. (2018) Estrogen-related receptor alpha is essential for maintaining mitochondrial integrity in cisplatin-induced acute kidney injury. Biochem Biophys Res Commun 498(4):918-924 |
| abstractText | Acute kidney injury (AKI) has been associated with not only higher in-hospital mortality but also the subsequent development of chronic kidney disease (CKD). Recent evidence has suggested the involvement of mitochondrial dysfunction and impaired dynamics in the pathogenesis of AKI. Estrogen-related receptor alpha (ERRalpha) is an orphan nuclear receptor that acts as a transcription factor to regulate the transcription of genes required for mitochondrial biogenesis and oxidative phosphorylation. In the present study, we examined the effects of ERRalpha deficiency on the progression of AKI induced by cisplatin. Male C57BL/6J wild-type and ERRalpha(-/-) mice received a single intraperitoneal injection of 20mg/kg cisplatin. Seventy-two hours after the injection, kidney function and morphology were evaluated. ERRalpha expression was observed in renal tubules, and cisplatin inhibited its translocation into nuclei. ERRalpha deficiency exacerbated cisplatin-induced renal dysfunction and tubular injury, as well as oxidative stress and apoptosis. ERRalpha(-/-) mice kidneys revealed lower mitochondrial DNA content and swollen mitochondria with reduced cristae. In addition, these mice had lower expression of the mitochondrial fusion protein mitofusin-2. The cisplatin-induced decrease in mitochondrial DNA and altered mitochondrial structure were more severe in ERRalpha(-/-) mice. In cultured mouse proximal tubular epithelial cells, the ERRalpha inverse agonist XCT-790 significantly inhibited mitofusin-2 expression and induced mitochondrial fragmentation. Taken together, our findings suggest the involvement of ERRalpha in the progression of cisplatin-induced AKI probably through impaired mitochondrial dynamics. |
