Effects of lysophosphatidylcholine on cultured heart cells: correlation of rate of uptake and extent of accumulation with cell injury.
In this study we evaluated the effects of lysophosphatidylcholine, a possible mediator of ischemic damage, on cultured neonatal rat heart cells. The rate and duration of lysophosphatidylcholine accumulation was correlated with Ca++ uptake and cell injury. The rate of carbon 14-labeled lysophosphatidylcholine accumulation during superfusion of the cells by 10 to 100 mumol/L 14C-labeled lysophosphatidylcholine was proportional to the concentration of lysophosphatidylcholine in the perfusate. Rapid accumulation of lysophosphatidylcholine (0.235 nmol/mg protein per minute), which occurred during 10 minutes of exposure to 100 mumol/L lysophosphatidylcholine, resulted in Ca++ overload and cell lysis. In contrast, slow accumulation of lysophosphatidylcholine by myocytes, which occurred during prolonged (1 hour) exposure to a sublethal micellar concentration (80 mumol/L) or very prolonged exposure (6 hours) to a submicellar concentration of lysophosphatidylcholine (10 mumol/L) did not result in Ca++ overload or irreversible injury despite more total lysophosphatidylcholine accumulation than during a single 10-minute exposure to 100 mumol/L lysophosphatidylcholine (p less than 0.005). Repeated brief exposures (5 minutes) to 100 mumol/L lysophosphatidylcholine separated by 20-minute recovery intervals also resulted in more lysophosphatidylcholine accumulation than during the lethal 10-minute exposure to 100 mumol/L lysophosphatidylcholine but did not result in irreversible injury. We therefore conclude that cardiac myocytes can tolerate slow accumulation of lysophosphatidylcholine and that factors other than the quantity of lysophosphatidylcholine accumulating in cells are determinants of the degree of injury sustained from exposure to lysophosphatides.
Sedlis
S P
SP
SUNY Downstate Medical Center, Brooklyn.
Sequeira
J M
JM
Ahumada
G G
GG
el Sherif
N
N
D000818:Animals; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D003327:Coronary Disease / Q000378:metabolism; D006321:Heart / Q000187:drug effects; D008244:Lysophosphatidylcholines / Q000378:metabolism* / Q000633:toxicity; D009206:Myocardium / Q000378:metabolism*; D051381:Rats; D012508:Sarcolemma / Q000378:metabolism
D008244:Lysophosphatidylcholines; D002118:Calcium