Journal
JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS
Volume 315, Issue 3, Pages 1125-1135Publisher
AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS
DOI: 10.1124/jpet.105.090803
Keywords
-
Categories
Funding
- NHLBI NIH HHS [HL-57787, HL-67745] Funding Source: Medline
- NICHD NIH HHS [HD-31226] Funding Source: Medline
Ask authors/readers for more resources
Previous studies have reported the sex differences in heart susceptibility to ischemia/reperfusion (I/R) injury, but the mechanisms are not understood. The present study tested the hypothesis that Akt and protein kinase C (PKC)epsilon play an important role in the sexual dimorphism of heart susceptibility to I/R injury. Isolated hearts from 2-month-old male and female rats were subjected to I/R in the Langendorff preparation. The post-ischemic recovery of left ventricular function was significantly better, and infarct size was significantly smaller in female (37.1 +/- 1.9%) than in male (48.3 +/- 2.3%) hearts after 25-min ischemia followed by 2-h reperfusion. Inhibition of phosphatidylinositol 3-kinase/Akt pathway by wortmannin or PKC by chelerythrine chloride before ischemia significantly reduced postischemic recovery and increased infarct size in female but not male hearts. There were no differences in myocardial protein levels of heat shock protein 70, Akt, and PKC epsilon, respectively, between male and female rats. However, the ratio of phosphorylated (p)-Akt/Akt (0.58 +/- 0.05 versus 0.22 +/- 0.04; P < 0.05) and p-PKC epsilon/PKC epsilon (0.35 +/- 0.03 versus 0.22 +/- 0.02; P < 0.05) was significantly higher in female than in male hearts. In addition, there were significant increases in p-Akt and pPKC epsilon levels during reperfusion in female but not in male hearts. The results suggest that increased p-Akt and p-PKC epsilon levels in female hearts contribute to the gender-related differences in heart susceptibility to I/R and play an important role in cardio-protection against I/R injury in females.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available