Effect of age on the expression of phosphoenolpyruvate carboxykinase in rat liver

T Wimonwatwatee1, A R Heydari, W T Wu

  • 1Department of Chemistry, Illinois State University, Normal 61761.

Insights

Aging reduces phosphoenolpyruvate carboxykinase (PEPCK) expression in rat liver and kidney. This decline is primarily due to decreased PEPCK gene transcription, not mRNA stability.

Area of Science:

  • Biogerontology
  • Molecular Endocrinology
  • Metabolic Regulation

Background:

  • Phosphoenolpyruvate carboxykinase (PEPCK) is a key gluconeogenic enzyme.
  • Age-related metabolic changes can impact enzyme expression and function.

Purpose of the Study:

  • To investigate the effect of aging on PEPCK expression in rat hepatocytes and kidney tissue.
  • To determine the molecular mechanisms underlying age-related changes in PEPCK levels.

Main Methods:

  • Hepatocytes and kidney tissue were isolated from Fischer 344 rats of different ages (6, 15, 26 months) after fasting.
  • PEPCK activity was measured using enzyme assays.
  • PEPCK mRNA levels were quantified.
  • mRNA stability and nuclear transcription rates were assessed.

Main Results:

  • PEPCK activity and mRNA levels significantly decreased with age in both liver and kidney tissues.
  • The stability of PEPCK mRNA remained similar between young and old rats.
  • Nuclear transcription of PEPCK was significantly lower in hepatocytes from older rats.

Conclusions:

  • The age-related decline in PEPCK expression in rat liver and kidney is primarily caused by reduced gene transcription.
  • This decreased transcription leads to lower PEPCK mRNA levels and consequently reduced enzyme activity.
  • These findings highlight a molecular basis for age-associated alterations in gluconeogenesis.

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