Myocardial ischemia and reperfusion reduce the levels of cyclic ADP-ribose in rat myocardium.

Abstract

Cyclic ADP-ribose (cADPR) is a novel Ca(2+)-mobilizing second messenger in mammalian cells including cardiomyocytes. It is unknown whether myocardial ischemia and reperfusion affect the metabolism of cADPR in the myocardium. The present study therefore examined the effects of myocardial ischemia and reperfusion on the concentrations of myocardial cADPR using high-performance liquid chromatography. Basal levels of cADPR in rat myocardium were 5.3 +/- 1.8 nmol x mg(-1) protein. Myocardial ischemia for 30 min significantly decreased cADPR concentrations to 2.1 +/- 0.4 nmol x mg(-1) protein. During reperfusion, cADPR was maintained at ischemic levels. The activity of ADP-ribosyl cyclase was expressed as the conversion rate of nicotinamide guanine dinucleotide (NGD(+)) to cyclic GDP-ribose. Myocardial ischemia and reperfusion did not alter the activity of ADP-ribosyl cyclase. However, cADPR hydrolase activity, as measured by the conversion rate of cADPR to ADP-ribose, was significantly elevated by ischemia and reperfusion. To determine the mechanism resulting in the enhancement of cADPR hydrolase activity, we examined the effects of changes in ADP, ATP, pH, and PO(2) on the conversion rate of cADPR to ADPR. Alterations of ADP, ATP, or pH in myocardial tissue had no effect on the degradation of cADPR, whereas a decrease in tissue PO(2) markedly increased the hydrolysis of cADPR. These results suggest that myocardial ischemia and reperfusion decrease cADPR in the myocardium by increasing its hydrolysis. Tissue hypoxia may be one of the important mechanisms to activate cADPR hydrolase.

• Authors: Zhi-Dong Ge, Pin-Lan Li, Ya-Fei Chen, Garrett J Gross, Ai-Ping Zou
• Journal: Basic research in cardiology (Basic Res Cardiol) Vol. 97 Issue 4 Pg. 312-9 (Jul 2002) ISSN: 0300-8428 [Print] Germany
• PMID: 12111041 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Cyclic ADP-Ribose
• Adenosine Diphosphate
• Adenosine Triphosphate
• ADP-ribosyl Cyclase
• Oxygen

Topics

• ADP-ribosyl Cyclase (metabolism)
• Adenosine Diphosphate (pharmacology)
• Adenosine Triphosphate (pharmacology)
• Animals
• Cyclic ADP-Ribose (metabolism)
• Enzyme Activation (drug effects, physiology)
• Hydrogen-Ion Concentration
• Male
• Myocardial Infarction (metabolism)
• Myocardial Reperfusion Injury (metabolism)
• Myocardium (metabolism)
• Oxygen (pharmacology)
• Rats
• Rats, Wistar