Low level of sarcolemmal phosphatidylinositol 4,5-bisphosphate in cardiomyopathic hamster (UM-X7.1) heart

Attila Ziegelhoffer, Paramjit S. Tappia, Nasrin Mesaeli, Nidhi Sahi, Naranjan S. Dhalla, Vincenzo Panagia

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

Objective: Phosphatidylinositol 4,5-bisphosphate (PtdIns 4,5-P2) is not only a precursor to inositol 1,4,5-trisphosphate (Ins 1,4,5-P3) 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-P2 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-P2 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), PLC δ1 isoenzyme activity in the SL membrane was elevated, with a concomitant increase in its protein content, whereas PLC β1 and γ1 isoenzyme activities were depressed despite the increase in their protein levels. A 2-fold increase in the Ins 1,4,5-P3 concentration in the cytosol of the failing heart of CMPH was also observed. Conclusions: Reduced SL level of PtdIns 4,5-P2 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-P3 levels may contribute to intracellular Ca2+ overload in the failing cardiomyocyte. (C) 2001 Elsevier Science B.V.

Original languageEnglish
Pages (from-to)118-126
Number of pages9
JournalCardiovascular Research
Volume49
Issue number1
DOIs
Publication statusPublished - 1 Jan 2001

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Keywords

  • Cardiomyopathy
  • Heart failure
  • Myocytes
  • Sarcolemma
  • Second messenger
  • Signal transduction

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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