Key result
Hyperglycaemia-induced oxidative stress and MAPK activation decreased cardiac PPARdelta expression in streptozotocin-diabetic rats and cultured cardiomyocytes.
Why the study?
Does hyperglycaemia-induced oxidative stress reduce cardiac PPARdelta expression in diabetic cardiomyopathy models?
Does hyperglycaemia-induced oxidative stress reduce cardiac PPARdelta expression in diabetic cardiomyopathy models?
Hyperglycaemia-induced oxidative stress and MAPK activation reduce cardiac PPARdelta expression, suggesting a mechanism for the development of diabetic cardiomyopathy.
May suppress cardiac PPARdelta via oxidative stress in diabetic rats; leaves open therapeutic targeting in human cardiomyopathy.
AIMS: The role of peroxisome proliferator-activated receptor delta (PPARdelta) in the development of cardiomyopathy, which is widely observed in diabetic disorders, is likely because cardiomyocyte-restricted PPARdelta deletion causes cardiac hypertrophy. Thus, we investigated the effect of hyperglycaemia-induced oxidative stress on the expression of cardiac PPARdelta both in vivo and in vitro. METHODS AND RESULTS: We used male Wistar rats to examine the effect of hyperglycaemia on PPARdelta expression in streptozotocin-induced diabetic rats, primary neonatal rat cardiomyocytes, and H9c2 embryonic rat cardiomyocytes. PPARdelta 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 alpha-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 PPARdelta expression. Also, ROS production, cell size, and protein synthesis were increased while PPARdelta 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 PPARdelta expression in response to hyperglycaemia.
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Yu et al. (2008) studied Cardiomyopathy in diabetes. Hyperglycaemia / streptozotocin-induced diabetes vs. Normoglycaemia / non-diabetic controls was evaluated on PPARdelta expression, ROS production, cell size, and protein synthesis. Hyperglycaemia-induced oxidative stress and MAPK activation decreased cardiac PPARdelta expression in streptozotocin-diabetic rats and cultured cardiomyocytes.
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