Cardiovascular Research Advance Access first published online on June 23, 2008
This version [Corrected Proof] published online on July 9, 2008
Cardiovascular Research, doi:10.1093/cvr/cvn172
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Decrease of peroxisome proliferator-activated receptor delta expression in cardiomyopathy of streptozotocin-induced diabetic rats
1 Institute of Basic Medical Sciences, College of Medicine, National Cheng Kung University, Tainan, Taiwan 70101, ROC
2 Department of Surgery, Mackay Memorial Hospital, Graduate Institute of Injury Prevention and Control, Taipei Medical University, Taipei, Taiwan 10407, ROC
3 Department of Internal Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan 70101, ROC
4 Department of Pharmacology, College of Medicine, National Cheng Kung University, 1, University Road, Tainan, Taiwan 70101, ROC
* Corresponding author. Tel: +886 6 237 2706; fax: +886 6 238 6548. E-mail address: jtcheng{at}mail.ncku.edu.tw
Aims: The role of peroxisome proliferator-activated receptor delta (PPAR
) in the development of cardiomyopathy, which is widely observed in diabetic disorders, is likely because cardiomyocyte-restricted PPAR deletion causes cardiac hypertrophy. Thus, we investigated the effect of hyperglycaemia-induced oxidative stress on the expression of cardiac PPAR both in vivo and in vitro.
Methods and results: We used male Wistar rats to examine the effect of hyperglycaemia on PPAR expression in streptozotocin-induced diabetic rats, primary neonatal rat cardiomyocytes, and H9c2 embryonic rat cardiomyocytes. PPAR mRNA (messenger ribonucleic acid) and protein levels were measured using northern and western blotting, respectively. The lipid deposition within the heart section was assessed by oil red O staining. The formation of reactive oxygen species (ROS) and changes in morphology, protein synthesis, and 
-actinin content in hyperglycaemic cells were also examined. Inhibitors of ROS production or mitogen-activated protein kinase (MAPK) activation were employed to investigate the possible mechanisms. Cardiomyopathy induced in streptozotocin-diabetic rats was associated with a marked decrease in cardiac PPAR expression. Also, ROS production, cell size, and protein synthesis were increased while PPAR expression was reduced in cells exposed to hyperglycaemia in vitro. However, these glucose-induced changes were abolished in the presence of tiron or PD98059 (MEK/ERK inhibitor).
Conclusion: Our results suggest that inhibitors of ROS production or MAPK activation are involved in reduction of cardiac PPAR expression in response to hyperglycaemia.
KEYWORDS Cardiomyopathy; Diabetes; Gene expression; Oxygen radicals; Cell culture
Time for primary review: 29 days