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Human catalase gene is regulated by peroxisome proliferator activated receptor-gamma through a response element

Yosuke Okuno1, Morihiro Matsuda, Yugo Miyata

  • 1Department of Metabolic Medicine, Graduate School of Medicine, Osaka University, Osaka, Japan.

Endocrine Journal
|January 16, 2010
PubMed

Insights

Peroxisome proliferator-activated receptor gamma (PPARgamma) agonists reduce oxidative stress by upregulating catalase. This study identifies a novel PPARgamma response element in human catalase gene regulation, distinct from mouse mechanisms.

Area of Science:

  • Molecular Biology
  • Endocrinology
  • Biochemistry

Background:

  • Oxidative stress is a key factor in atherosclerosis and diabetic complications, including beta-cell failure.
  • Peroxisome proliferator-activated receptor gamma (PPARgamma) agonists improve insulin sensitivity and combat oxidative stress.
  • Catalase, a crucial antioxidant enzyme, is regulated by PPARgamma in mice.

Purpose of the Study:

  • To investigate the regulatory mechanisms of catalase gene expression in humans.
  • To determine if PPARgamma regulates human catalase expression similarly to mouse models.
  • To identify the specific DNA elements involved in human catalase gene regulation by PPARgamma.

Main Methods:

  • Treatment of human primary adipocytes with a PPARgamma agonist.
  • Luciferase reporter assays using human catalase promoter constructs.
  • Electrophoretic mobility shift assays (EMSA) to confirm protein-DNA binding.

Main Results:

  • Catalase expression was significantly increased in human adipocytes treated with a PPARgamma agonist.
  • The PPARgamma binding elements found in the mouse catalase promoter were not conserved in humans.
  • A novel PPARgamma response element (PPRE) located at -12 kb in the human catalase promoter was identified, mediating transactivation by PPARgamma/RXRalpha.

Conclusions:

  • PPARgamma regulates human catalase gene expression through a distinct PPRE compared to mice.
  • This novel regulatory mechanism contributes to the understanding of how PPARgamma inhibits oxidative stress in humans.
  • Findings may explain the therapeutic benefits of PPARgamma agonists in conditions associated with oxidative stress.

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