Identification of changes in cardiac phospholipase C activity in congestive heart failure.
Although phosphoinositide-specific phospholipase C (PLC) is involved in signal transduction mechanisms of the myocardial cell. very little is known about its status in congestive heart failure (CHF). We have examined the PLC activity in sarcolemmal and cytosolic fractions isolated from the viable left ventricle of rats at 8 weeks (moderate stage of CHF) and 16 weeks (severe stage of CHF) after occlusion of the left anterior descending coronary artery; the hypertrophied right ventricle was used for comparison. At 8 weeks, the hydrolysis of phosphatidylinositol 4,5-bisphosphate by sarcolemmal PLC was reduced by 37% of sham control values only in the left ventricle, whereas at 16 weeks, PLC-mediated hydrolysis was depressed in both left and right ventricles by 25% and 30%, respectively. The hydrolysis of phosphatidylinositol 4-monophosphate (PIP) was reduced by 25% of control value only in the severely failing left ventricle, while the phosphatidylinositol (PI) hydrolysis remained unaltered. Kinetic studies of PLC activity in the left ventricle showed a depression of V(max) at moderate and severe failure stages, whereas the affinity for the substrate was increased in the left ventricle at 8 weeks and decreased in the right ventricle at 16 weeks. The only difference observed between experimental and control groups at the cytosolic level, was a significant enhancement of PLC activity in the severely failing left ventricle when PIP was given as a substrate, and in the corresponding right ventricle when PI was the substrate. The results of this study identify time-related defects in sarcolemmal PLC in right and left ventricles during the development of CHF due to myocardial infarction.
Meij
J T
JT
Department of Anatomy, Faculty of Medicine, University of Manitoba, Winnipeg, Canada.
Panagia
V
V
Mesaeli
N
N
Peachell
J L
JL
Afzal
N
N
Dhalla
N S
NS
D000704:Analysis of Variance; D000818:Animals; D003600:Cytosol / Q000201:enzymology*; D006333:Heart Failure / Q000201:enzymology* / Q000473:pathology; D006352:Heart Ventricles / Q000201:enzymology*; D006439:Hemodynamics / Q000502:physiology; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D012508:Sarcolemma / Q000201:enzymology*; D010738:Type C Phospholipases / Q000378:metabolism*
D010738:Type C Phospholipases