Egr-1, the potential target of calcium channel blockers in cardioprotection with ischemia/reperfusion injury in rats.
OBJECTIVE
In this study, we tested whether Egr-1 is a potential target of calcium channel blockers in cardioprotection with I/R injury.


METHODS
We treated rats in vivo I/R and rat cultured cardiomyocytes in vitro hypoxia/reoxygenation (H/R) models with three types of classical calcium channel blockers (verapamil, diltiazem and nifedipine). Activity of creatine kinase (CK), lactate dehydrogenase (LDH), myeloperoxidase (MPO) superoxide dismutase (SOD) and level of malondialdehyde (MDA) in plasma and culture medium were measured to assess the degree of injury and inflammation of myocardial tissues and cells. Egr-1 mRNA and protein expressions were examined by RT-PCR and Western-blot analyses.


RESULTS
Calcium channel blockers (verapamil, diltiazem and nifedipine) significantly attenuated myocardial injury, as shown by reduced release of CK and LDH, preserved SOD activity and decreased MDA production and MPO activity. Concomitant with cardioprotection by calcium channel blockers, the mRNA and protein expression of Egr-1 increased with I/R and H/R injury was significantly reduced in myocardial tissue and cultured cardiomyocytes.


CONCLUSIONS
These results suggested that the cardioprotective effects of calcium channel blockers with I/R or H/R injury might be mediated by downregulating Egr-1 expression. Egr-1 might be the potential target of calcium channel blockers in cardioprotection with ischemia/reperfusion injury.
Huang
Zhanqin
Z
Department of Pharmacology, First Affiliated Hospital, Shantou University Medical College, Shantou, China.
Li
Haiqing
H
Guo
Fuxiao
F
Jia
Qiangyong
Q
Zhang
Yanmei
Y
Liu
Xingping
X
Shi
Ganggang
G
D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D002478:Cells, Cultured; D003402:Creatine Kinase / Q000032:analysis / Q000097:blood; D015536:Down-Regulation; D051766:Early Growth Response Protein 1 / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D000860:Hypoxia / Q000378:metabolism; D007770:L-Lactate Dehydrogenase / Q000032:analysis / Q000097:blood; D008297:Male; D008315:Malondialdehyde / Q000032:analysis / Q000097:blood; D015428:Myocardial Reperfusion Injury / Q000235:genetics / Q000378:metabolism*; D032383:Myocytes, Cardiac / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013482:Superoxide Dismutase / Q000032:analysis / Q000097:blood
D002121:Calcium Channel Blockers; D051766:Early Growth Response Protein 1; C486110:Egr1 protein, rat; D008315:Malondialdehyde; D007770:L-Lactate Dehydrogenase; D013482:Superoxide Dismutase; D003402:Creatine Kinase