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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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