Decrease of peroxisome proliferator-activated receptor delta expression in cardiomyopathy of streptozotocin-induced diabetic rats

Bu Chin Yu, Chen Kuei Chang, Horng Yih Ou, Kai Chun Cheng, Juei Tang Cheng

Research output: Contribution to journalArticle

61 Citations (Scopus)

Abstract

Aims: The role of peroxisome proliferator-activated receptor delta (PPARδ) in the development of cardiomyopathy, which is widely observed in diabetic disorders, is likely because cardiomyocyte-restricted PPARδ deletion causes cardiac hypertrophy. Thus, we investigated the effect of hyperglycaemia-induced oxidative stress on the expression of cardiac PPARδ both in vivo and in vitro. Methods and results: We used male Wistar rats to examine the effect of hyperglycaemia on PPARδ expression in streptozotocin-induced diabetic rats, primary neonatal rat cardiomyocytes, and H9c2 embryonic rat cardiomyocytes. PPARδ 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 α-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 PPARδ expression. Also, ROS production, cell size, and protein synthesis were increased while PPARδ 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 PPARδ expression in response to hyperglycaemia.

Original languageEnglish
Pages (from-to)78-87
Number of pages10
JournalCardiovascular Research
Volume80
Issue number1
DOIs
Publication statusPublished - 2008 Oct 1

All Science Journal Classification (ASJC) codes

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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