Calmodulin-dependent cyclic nucleotide phosphodiesterase in an experimental rat model of cardiac ischemia-reperfusion.
In the present study, we investigated the activity and expression of calmodulin-dependent cyclic nucleotide phosphodiesterase (CaMPDE) and the effects of calpains in rat heart after ischemia and reperfusion. Immunohistochemical studies indicated that CaMPDE in normal heart is localized in myocardial cells. Rat ischemic heart showed a decrease in CaMPDE activity in the presence of Ca2+ and calmodulin; however, in ischemic-reperfusion tissue a progressive increase in Ca2+ and calmodulin-independent cyclic nucleotide phosphodiesterase (CaM-independent PDE) activity was observed. Perfusion of hearts with cell-permeable calpain inhibitor suppressed the increase of Ca2+ and CaM-independent PDE activity. Protein expression of CaMPDE was uneffected by hypoxic injury to rat myocardium. The purified heart CaMPDE was proteolyzed by calpains into a 45 kDa immunoreactive fragment in vitro. Based on these results, we propose that hypoxic injury to rat myocardium results in the generation of CaM-independent PDE by calpain mediated proteolysis, allowing the maintenance of cAMP concentrations within the physiological range.
Kakkar
Rakesh
R
Department of Pathology, College of Medicine, University of Saskatchewan, Saskatoon, Canada.
Seitz
Dallas P
DP
Kanthan
Rani
R
Rajala
Raju V S
RV
Radhi
Jasim M
JM
Wang
Xinto
X
Pasha
Mohammed K
MK
Wang
Rui
R
Sharma
Rajendra K
RK
D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000378:metabolism*; D000818:Animals; D015153:Blotting, Western; D002154:Calpain / Q000037:antagonists & inhibitors; D002417:Cattle; D000242:Cyclic AMP / Q000378:metabolism; D054677:Cyclic Nucleotide Phosphodiesterases, Type 1; D007150:Immunohistochemistry; D019157:Ischemic Preconditioning, Myocardial; D008297:Male; D015428:Myocardial Reperfusion Injury / Q000201:enzymology*; D009206:Myocardium / Q000201:enzymology; D051381:Rats; D017207:Rats, Sprague-Dawley
D000242:Cyclic AMP; D015105:3',5'-Cyclic-AMP Phosphodiesterases; D054677:Cyclic Nucleotide Phosphodiesterases, Type 1; D002154:Calpain