PPARα agonist prevented the apoptosis induced by glucose and fatty acid in neonatal cardiomyocytes.
OBJECTIVE
We investigated the effect of peroxisome proliferator activator receptors α (PPARα) on cardiomyocyte apoptosis induced by glucose and fatty acid, and if high glucose levels could increase fatty acid-induced apoptosis.


METHODS
Cardiomyocytes were maintained in Dulbecco's Modified Eagle Medium and divided into 5 groups: Group N (control Group); Group G (exposed to 25.5 mmol/l glucose); Group L (exposed to 5 mmol/l glucose, fatty acid); Group H (exposed to 25.5 mmol/l glucose and fatty acid); Group I (exposed to 25.5 mmol/l glucose, fatty acid and Wy14643). Apoptosis was detected by terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling. Immunocytochemistry staining detected PPARα's expressing, and western blotting detected PPARα and nuclear factor κB's (NF-κB) protein level.


RESULTS
Exposure to fatty acid resulted in a significant increase of cardiomyocytes apoptosis, with the extension of NF-κB formation, whereas exposure to 25.5 mmol/l glucose had no influence on the apoptosis rate. However, combination with fatty acid and high glucose concentration had induced more apoptosis with the up-regulation of NF-κB formation. The fatty acid and glucose-induced effects were improved by Wy14643, with down-regulation of NF-κB formation.


CONCLUSIONS
These results suggested that in neonatal cardiomyocytes, fatty acid and glucose in combination with fatty acid induced apoptosis via NF-κB formation and activation of apoptosis pathways; glucose in combination with fatty acid induce more apoptosis rate for the more NF- κB formation, activation of the PPARα can reverse such apoptosis effect. The results also suggest that gluco-lipotoxicity may play a central role in the development of diabetic cardiomyopathy, and PPARα-agonist may be an effective drug in treating the diabetic cardiomyopathy.
Nan
W Q
WQ
Department of Gerontology, First Affiliated Hospital of ChongQing Medical University, Chongqing City, China.
Shan
T Q
TQ
Qian
X
X
Ping
W
W
Bing
G A
GA
Ying
L L
LL
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002478:Cells, Cultured; D005227:Fatty Acids / Q000494:pharmacology*; D005947:Glucose / Q000494:pharmacology*; D006801:Humans; D020287:In Situ Nick-End Labeling; D032383:Myocytes, Cardiac / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D047493:PPAR alpha / Q000819:agonists* / Q000378:metabolism; D020025:Peroxisome Proliferators / Q000494:pharmacology; D011743:Pyrimidines / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley
D005227:Fatty Acids; D016328:NF-kappa B; D047493:PPAR alpha; D020025:Peroxisome Proliferators; D011743:Pyrimidines; C006253:pirinixic acid; D005947:Glucose