Annexins in cardiac tissue: cellular localization and effect on phospholipase activity.
Stimulation of cardiac phospholipid metabolism has diverse biological effects, ranging from subtle changes in cellular function to severe cellular damage. Accordingly, knowledge of the factors governing the activity of cardiac phospholipases is of great biological importance. A possible role of annexins, intracellular proteins that bind to membranes in a calcium dependent manner, as modulators of phospholipase activity has been proposed. In this study we investigated the cell type specific distribution of Annexin V and VIII in the heart. Recombinant Annexin V was used to examine the effect of this type of Annexin on cardiac phospholipase activity. Western blot analysis shows that annexin V is abundantly present in the heart. Using isolated myocytes and cultured cardiac endothelial and fibroblast-like cells, it is demonstrated that the localization of Annexin V is confined to non-myocytes. No positive bands matching the Mw of recombinant Annexin VIII are found in any of the cell types examined. In vitro studies demonstrate that recombinant Annexin V potently inhibits the activity of cardiac membrane-bound phospholipases, acting on their natural surrounding substrate, in a calcium dependent manner. Interestingly, annexin V also inhibits triacylglycerol hydrolysis. In conclusion, the expression of annexins is cell-type specific and suggests a cell-type specific function of these proteins in the heart. The absence of Annexin V in cardiac myocytes dismisses involvement of this annexin in cardiomyocyte phospholipid metabolism. The presence of Annexin V in cardiac endothelial and fibroblasts suggests a regulating role in the phospholipid homeostasis of non-myocyte cell types in the heart.
van Bilsen
M
M
Department of Physiology, University of Limburg, Maastricht, The Netherlands.
Reutelingsperger
C P
CP
Willemsen
P H
PH
Reneman
R S
RS
van der Vusse
G J
GJ
D000818:Animals; D017304:Annexin A5 / Q000378:metabolism*; D017302:Annexins / Q000378:metabolism*; D016718:Arachidonic Acid / Q000378:metabolism; D002118:Calcium / Q000494:pharmacology; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D009928:Organ Specificity; D010740:Phospholipases / Q000378:metabolism*; D010743:Phospholipids / Q000378:metabolism*; D051381:Rats; D011917:Rats, Inbred Lew; D011994:Recombinant Proteins / Q000378:metabolism; D014280:Triglycerides / Q000378:metabolism
D017304:Annexin A5; D017302:Annexins; D010743:Phospholipids; D011994:Recombinant Proteins; D014280:Triglycerides; D016718:Arachidonic Acid; D010740:Phospholipases; D002118:Calcium