Phosphatidylethanolamine and sarcolemmal damage during ischemia or metabolic inhibition of heart myocytes.
Phosphatidylethanolamine (PE) is a nonbilayer-preferring and fusogenic phospholipid. It is kept in the bilayer configuration by interaction with other phospholipids in biologic membranes. However, reorganization of the membrane phospholipids could lead to expression of the nonbilayer nature of PE and induce bilayer instability. During ischemia a transbilayer reorganization of sarcolemmal PE is observed, and results have been published that suggest a lateral phase separation in the inner sarcolemmal leaflet phospholipids. These reorganizations and the subsequent expression of the nonbilayer behavior of PE are proposed to form the basis for sarcolemma destabilization and destruction. Lowering the PE content of myocytes, especially of the sarcolemma, is then expected to attenuate myocyte damage after simulated ischemia or metabolic inhibition. Culturing neonatal rat heart myocytes in the presence of N,N-dimethylethanolamine resulted in the synthesis of the bilayer-preferring N,N-dimethyl-PE and a lowering of the ratio between nonbilayer- and bilayer-preferring phospholipids from 0.58 to 0.30. This change in phospholipid composition did not impair cell functioning but did result in a strong attenuation of cell damage on ischemia or metabolic inhibition. A good correlation between the nonbilayer-preferring phospholipid content and the degree of cell damage was obtained (r = 0.98). These results provide further evidence that physicochemical properties of the sarcolemmal phospholipids play a crucial role in the sarcolemmal disruption during prolonged ischemia and/or reperfusion.
Post
J A
JA
Institute of Biomembranes, University of Utrecht, The Netherlands.
Bijvelt
J J
JJ
Verkleij
A J
AJ
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D002478:Cells, Cultured; D005021:Ethylamines / Q000494:pharmacology; D017202:Myocardial Ischemia / Q000378:metabolism* / Q000473:pathology*; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D010714:Phosphatidylethanolamines / Q000378:metabolism*; D010743:Phospholipids / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012508:Sarcolemma / Q000473:pathology*
D005021:Ethylamines; D010714:Phosphatidylethanolamines; D010743:Phospholipids; D000255:Adenosine Triphosphate; C047305:N,N-dimethylethylamine