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

研究成果: 雜誌貢獻文章同行評審

31 引文 斯高帕斯(Scopus)

摘要

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.
原文英語
頁(從 - 到)692-699
頁數8
期刊European Journal of Clinical Investigation
40
發行號8
DOIs
出版狀態已發佈 - 八月 2010

ASJC Scopus subject areas

  • 醫藥 (全部)
  • 臨床生物化學
  • 生物化學

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