Knockout of the circadian clock protein PER1 results in sex-dependent alterations of ET-1 production in mice in response to a high-salt diet plus mineralocorticoid treatment

May 22, 2020Canadian journal of physiology and pharmacology

Removing the body clock protein PER1 changes ET-1 levels differently in male and female mice after high salt and hormone treatment

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Abstract

Male global PER1 knockout mice show a decreased night/day ratio of urinary endothelin-1 (ET-1).

  • Significant differences in ET-1 and its receptor expression were observed in male PER1 knockout mice but not in females when subjected to a high-salt diet plus mineralocorticoid treatment.
  • Both male wild-type and global PER1 knockout mice significantly increased endothelin B receptor expression in response to the treatment, while female mice did not.
  • Knockdown of PER1 in mouse kidney cells led to increased ET-1 mRNA expression and peptide secretion upon aldosterone treatment.
  • PER1 may serve as a negative regulator of ET-1 expression in the context of high-salt diet and mineralocorticoid treatment.

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