title: Oxidative stress and inflammation modulate peroxisome proliferator-activated receptors with regional discrepancy in diabetic heart.
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.
  
  
  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)-alpha 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-alpha was most expressed, and PPAR-gamma least expressed in mRNA and protein levels. Diabetes decreased the protein and mRNA levels of PPAR-alpha and PPAR-delta. Ascorbate attenuated the diabetes-induced down-regulations of PPAR-alpha and PPAR-delta proteins in all cardiac regions and down-regulation of PPAR-alpha mRNA in the left atrium. In PPAR-gamma, the protein and mRNA levels were increased in diabetic atria and ventricles, which were decreased by ascorbate. Moreover, diabetes increased the TNF-alpha and IL-6 protein levels, and NAD(P)H oxidase activities in atria and ventricles. Ascorbate attenuated the increase of TNF-alpha, 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.
authors.affiliation: Taipei Medical University, Taipei, Taiwan.
authors.forename: Ting-I
authors.initials: TI
authors.lastname: Lee
authors.forename: Yu-Hsun
authors.initials: YH
authors.lastname: Kao
authors.forename: Yao-Chang
authors.initials: YC
authors.lastname: Chen
authors.forename: Nan-Hung
authors.initials: NH
authors.lastname: Pan
authors.forename: Yi-Jen
authors.initials: YJ
authors.lastname: Chen
mesh_terms: D000818:Animals; D015153:Blotting, Western; D003920:Diabetes Mellitus / Q000378:metabolism*; D015536:Down-Regulation; D006325:Heart Atria / Q000201:enzymology / Q000378:metabolism*; D006352:Heart Ventricles / Q000201:enzymology / Q000378:metabolism*; D007249:Inflammation / Q000503:physiopathology*; D015850:Interleukin-6 / Q000032:analysis; D008297:Male; D009249:NADP / Q000032:analysis; D018384:Oxidative Stress / Q000502:physiology*; D047492:Peroxisome Proliferator-Activated Receptors / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction; D048069:Tumor Necrosis Factors / Q000378:metabolism
chemical_list: D015850:Interleukin-6; D047492:Peroxisome Proliferator-Activated Receptors; D012333:RNA, Messenger; D048069:Tumor Necrosis Factors; D009249:NADP