Phospholipid degradation in energy-deprived cardiac myocytes: does annexin V play a role?
This study explored whether annexin V, a protein with established phospholipase A2 inhibiting properties, plays a role in the degradation of membrane phospholipids of adult cardiac myocytes during metabolic inhibition (20 mM 2-deoxyglucose and 1 mM iodoacetic acid). Experiments were carried out on isolated cardiac myocytes prelabeled with [14C]-arachidonic acid, which were subjected to metabolic inhibition for up to 240 min. Under control conditions, annexin V was found to be localised predominantly at the sarcolemma. After 120 min of metabolic inhibition, the release of lactate dehydrogenase (LDH) was still comparable with control cells, while morphological changes were already visible. After 240 min of metabolic inhibition, LDH release was significantly elevated compared to control cells incubated for the same period of time (35% v 20% of total cellular activity). All myocytes had lost their typical elongated shape and sarcolemmal "blebs" had been formed. In metabolically inhibited cells, annexin V localisation seemed to be more pronounced at the level of the sarcolemma compared to controls, whereas membrane phospholipid hydrolysis occurred at a significantly elevated rate, as evidenced by a significantly enhanced accumulation of labeled arachidonic acid within the cells. The present findings are not in favor of the hypothesis that the increase in net degradation of phospholipids in energy-deprived cardiac myocytes is caused by a loss of annexin V from the sarcolemma, which would increase the vulnerability of the sarcolemma to phospholipase A2 activity.
Jans
S W
SW
Department of Physiology, Cardiovascular Research Institute Maastricht, Maastricht University, The Netherlands.
Willems
J
J
van Bilsen
M
M
Reutelingsperger
C P
CP
van der Vusse
G J
GJ
D000818:Animals; D017304:Annexin A5 / Q000378:metabolism*; D016718:Arachidonic Acid / Q000378:metabolism; D002250:Carbon Radioisotopes; D002478:Cells, Cultured; D004734:Energy Metabolism; D005227:Fatty Acids / Q000378:metabolism; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008297:Male; D009206:Myocardium / Q000166:cytology / Q000378:metabolism*; D010743:Phospholipids / Q000378:metabolism*; D051381:Rats; D011917:Rats, Inbred Lew; D014280:Triglycerides / Q000378:metabolism
D017304:Annexin A5; D002250:Carbon Radioisotopes; D005227:Fatty Acids; D010743:Phospholipids; D014280:Triglycerides; D016718:Arachidonic Acid; D007770:L-Lactate Dehydrogenase