Low level of sarcolemmal phosphatidylinositol 4,5-bisphosphate in cardiomyopathic hamster (UM-X7.1) heart.
OBJECTIVE
Phosphatidylinositol 4,5-bisphosphate (PtdIns 4,5-P(2)) is not only a precursor to inositol 1,4,5-trisphosphate (Ins 1,4, 5-P(3)) and sn-1,2 diacylglycerol, but also essential for the function of several membrane proteins. The aim of this study was to evaluate the changes in the level of this phospholipid in the cell plasma membrane (sarcolemma, SL) of cardiomyopathic hamster (CMPH) heart.


METHODS
We examined the cardiac SL PtdIns 4,5-P(2) mass and the activities of the enzymes responsible for its synthesis and hydrolysis in 250-day-old UM-X7.1 CMPH at a severe stage of congestive heart failure (CHF) and in age-matched controls (Syrian Golden hamsters).


RESULTS
The SL PtdIns 4,5-P(2) mass in CMPH was reduced by 72% of the control value. The activities of PtdIns 4 kinase and PtdIns 4-P 5 kinase were depressed by 69 and 50% of control values, respectively. Although, the total phospholipase C (PLC) activity was moderately, although significantly, decreased (by 18% of control), PLCdelta(1) isoenzyme activity in the SL membrane was elevated, with a concomitant increase in its protein content, whereas PLCbeta(1) and gamma(1) isoenzyme activities were depressed despite the increase in their protein levels. A 2-fold increase in the Ins 1,4,5-P(3) concentration in the cytosol of the failing heart of CMPH was also observed.


CONCLUSIONS
Reduced SL level of PtdIns 4, 5-P(2) may severely jeopardize cardiac cell function in this hamster model of CHF. In addition, the profound changes in the profile of heart SL PLC isoenzyme could alter the complex second messenger responses of these isoenzymes, and elevated Ins 1,4,5-P(3) levels may contribute to intracellular Ca(2+) overload in the failing cardiomyocyte.
Ziegelhoffer
A
A
Institute of Cardiovascular Sciences, St. Boniface General Hospital Research Centre, Department of Human Anatomy and Cell Science and Department of Physiology, Faculty of Medicine, University of Manitoba, Winnipeg, Canada.
Tappia
P S
PS
Mesaeli
N
N
Sahi
N
N
Dhalla
N S
NS
Panagia
V
V
D019870:1-Phosphatidylinositol 4-Kinase / Q000378:metabolism; D000818:Animals; D015153:Blotting, Western; D006224:Cricetinae; D003600:Cytosol / Q000378:metabolism; D006333:Heart Failure / Q000201:enzymology / Q000378:metabolism*; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism; D007527:Isoenzymes / Q000378:metabolism; D008297:Male; D008647:Mesocricetus; D019269:Phosphatidylinositol 4,5-Diphosphate / Q000378:metabolism*; D012508:Sarcolemma / Q000201:enzymology / Q000378:metabolism*; D015290:Second Messenger Systems / Q000502:physiology; D010738:Type C Phospholipases / Q000378:metabolism
D007527:Isoenzymes; D019269:Phosphatidylinositol 4,5-Diphosphate; D015544:Inositol 1,4,5-Trisphosphate; D019870:1-Phosphatidylinositol 4-Kinase; D010738:Type C Phospholipases