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Transcriptional regulation of NHE3 and SGLT1 by the circadian clock protein Per1 in proximal tubule cells
How the body clock protein Per1 controls key salt and sugar transporters in kidney cells
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Abstract
Per1 knockout mice exhibit dramatically lower blood pressure than wild-type mice.
- Per1 regulates the expression of the Na(+)/H(+) exchanger 3 (NHE3) and sodium-glucose cotransporter 1 (SGLT1) in the kidney.
- Pharmacological blockade of nuclear Per1 entry results in decreased mRNA expression of SGLT1 and NHE3 in the renal cortex.
- Similar reductions in NHE3 and SGLT1 expression are observed in human kidney cells when Per1 activity is inhibited.
- Effects of Per1 on NHE3 and SGLT1 expression appear to occur at the transcription level.
- Per1 and the circadian protein CLOCK are found at the promoters of NHE3 and SGLT1, indicating direct regulation.
- Blockade of nuclear Per1 entry leads to decreased levels of NHE3 and SGLT1 proteins, which is associated with reduced Na(+)-K(+)-ATPase activity.
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