Oxidative stress and inflammation modulate peroxisome proliferator- activated receptors with regional discrepancy in diabetic heart

Ting I. Lee, Yu Hsun Kao, Yao Chang Chen, Nan Hung Pan, Yi Jen Chen

Research output: Contribution to journalArticle

28 Citations (Scopus)

Abstract

Background Peroxisome proliferator-activated receptors (PPARs) play a pivotal role in myocardial lipid and glucose homeostasis. We investigated the effects of diabetes on PPAR isoforms in different cardiac regions and explored whether proinflammatory cytokines or oxidative stress modulate PPARs in diabetic hearts. Materials and methods Male Wistar rats were separated into control, diabetes and ascorbate-treated diabetes groups. Real-time PCR and Western blot analysis were performed on PPAR isoforms, tumour necrosis factor (TNF)-α and interleukin (IL)-6, from left and right atria and ventricles. Nicotinamide adenine dinucleotide phosphate [NAD(P)H] oxidase activity was quantified through photometric measurements. Results In control hearts, PPAR-α was most expressed, and PPAR-γ least expressed in mRNA and protein levels. Diabetes decreased the protein and mRNA levels of PPAR-α and PPAR-δ. Ascorbate attenuated the diabetes-induced down-regulations of PPAR-α and PPAR-δ proteins in all cardiac regions and down-regulation of PPAR-α mRNA in the left atrium. In PPAR-γ, the protein and mRNA levels were increased in diabetic atria and ventricles, which were decreased by ascorbate. Moreover, diabetes increased the TNF-α and IL-6 protein levels, and NAD(P)H oxidase activities in atria and ventricles. Ascorbate attenuated the increase of TNF-α, IL-6 protein levels and NAD(P)H oxidase activity in the atria, but only attenuated the increase of NAD(P)H oxidase activities in the ventricles. Conclusions Peroxisome proliferator-activated receptor isoforms are differentially expressed in the atria and ventricles. Diabetes can modulate PPARs through increased inflammatory cytokines and oxidative stress, which are attenuated by ascorbate treatment.

Original languageEnglish
Pages (from-to)692-699
Number of pages8
JournalEuropean Journal of Clinical Investigation
Volume40
Issue number8
DOIs
Publication statusPublished - Aug 2010

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Keywords

  • Cardiomyocytes
  • diabetes mellitus
  • nicotinamide adenine dinucleotide phosphate oxidase
  • peroxisome proliferator-activated receptors
  • proinflammatory cytokines

ASJC Scopus subject areas

  • Medicine(all)
  • Clinical Biochemistry
  • Biochemistry

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