| First Author | Gumz ML | Year | 2010 |
| Journal | Biochim Biophys Acta | Volume | 1799 |
| Issue | 9 | Pages | 622-9 |
| PubMed ID | 20868778 | Mgi Jnum | J:170201 |
| Mgi Id | MGI:4944136 | Doi | 10.1016/j.bbagrm.2010.09.003 |
| Citation | Gumz ML, et al. (2010) Regulation of alphaENaC expression by the circadian clock protein Period 1 in mpkCCD(c14) cells. Biochim Biophys Acta 1799(9):622-9 |
| abstractText | The epithelial sodium channel (ENaC) mediates the fine-tuned regulation of external sodium (Na) balance. The circadian clock protein Period 1 (Per1) is an aldosterone-induced gene that regulates mRNA expression of the rate-limiting alpha subunit of ENaC (alphaENaC). In the present study, we examined the effect of Per1 on alphaENaC in the cortex, the site of greatest ENaC activity in the collecting duct, and examined the mechanism of Per1 action on alphaENaC. Compared to wild type mice, Per1 knockout mice exhibited a 50% reduction of steady state alphaENaC mRNA levels in the cortex. Importantly, siRNA-mediated knockdown of Per1 decreased total alphaENaC protein levels in mpkCCD(c14) cells, a widely used model of the murine cortical collecting duct (CCD). Per1 regulated basal alphaENaC expression and participated in the aldosterone-mediated regulation of alphaENaC in mpkCCD(c14) cells. Because circadian clock proteins mediate their effects as part of multi-protein complexes at E-box response elements in the promoters of target genes, the ability of Per1 to interact with these sequences from the alphaENaC promoter was tested. For the first time, we show that Per1 and Clock are present at an E-box response element found in the alphaENaC promoter. Together these data support an important role for the circadian clock protein Per1 in the direct regulation of alphaENaC transcription and have important implications for understanding the role of the circadian clock in the regulation of renal function. |
