Zinc modulates PPARγ signaling and activation of porcine endothelial cells

Purushothaman Meerarani, Gudrun Reiterer, Michal J Toborek, Bernhard Hennig

Research output: Contribution to journalArticle

57 Scopus citations

Abstract

Dietary zinc has potent antioxidant and anti-inflammatory properties and is a critical component of peroxisome proliferator-activated receptor (PPAR) gene expression and regulation. To assess the protective mechanisms of PPARγ in endothelial cell dysfunction and the role of zinc in the modulation of PPARγ signaling, cultured porcine pulmonary artery endothelial cells were exposed to the membrane-permeable zinc chelator N,N,N′N′-tetrakis (2-pyridylmethyl)-ethylene diamine (TPEN), thiazolidinedione (TZD; PPARγ agonist) or bisphenol A diglycidyl ether (BADGE; PPARγ antagonist). Subsequently, endothelial cells were activated by treatment with linoleic acid (90 μmol/L) for 6 h. Zinc chelation by TPEN increased the DNA binding activity of nuclear factor (NF)-κB and activator protein (AP)-1, decreased PPARγ expression and activation as well as up-regulated interleukin (IL)-6 expression and production. These effects were fully reversed by zinc supplementation. In addition, exposure to TZD down-regulated linoleic acid-induced DNA binding activity of NF-κB and AP-1, whereas BADGE further induced activation of these oxidative stress-sensitive transcription factors. Most importantly, the TZD-mediated down-regulation of NF-κB and AP-1 and reduced inflammatory response were impaired during zinc chelation. These data suggest that zinc plays a critical role in PPARκ signaling in linoleic acid-induced endothelial cell activation and indicate that PPARγ signaling is impaired during zinc deficiency.

Original languageEnglish
Pages (from-to)3058-3064
Number of pages7
JournalJournal of Nutrition
Volume133
Issue number10
StatePublished - Oct 1 2003
Externally publishedYes

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Keywords

  • Endothelial cells
  • Inflammation
  • Linoleic acid
  • PPARγ
  • Zinc

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Food Science

Cite this

Meerarani, P., Reiterer, G., Toborek, M. J., & Hennig, B. (2003). Zinc modulates PPARγ signaling and activation of porcine endothelial cells. Journal of Nutrition, 133(10), 3058-3064.