Phosphatidylethanolamine and sarcolemmal damage during ischemia or metabolic inhibition of heart myocytes

Abstract

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.

Differential Lipid Profiles in Experimental Steatohepatitis: Role for Imaging Mass Spectrometry as a Diagnostic Aid

“…Phosphatidylserines have critical cofactor roles in the binding and activation of signaling molecules, blood clotting factors, and apoptosis cascades [46]. Phosphatidylethanolamines are highly enriched in brain (45% of total phospholipids) [47], but they also play major roles in sustaining the integrity of cardiomyocytes [48]. Furthermore, phosphatidylethanolamines serve as substrates for phosphoethanolamine N-methyltransferase (PEMT), which is used in liver to convert phosphoethanolamine to phosphocholine [49].…”

The follicular microenviroment as a predictor of pregnancy: MALDI-TOF MS lipid profile in cumulus cells

“…First, PE is redistributed and transiently externalized during mitotic cell division [12], which may occur during proliferation of the CCs. PE is also redistributed and exposed to the extracellular environment that signals cell death when the membrane asymmetry is compromised [32]. Li et al described that the decrease in the ratio of PC to PE was associated with a reduction in membrane integrity (Caballero et al2010; [25]).…”

Thematic Review Series: Glycerolipids. Phosphatidylserine and phosphatidylethanolamine in mammalian cells: two metabolically related aminophospholipids

“…For example, PE metabolism in the heart appears to be important, because the asymmetrical transbilayer distribution of PE in sarcolemmal membranes is altered during ischemia, leading to sarcolemmal disruption (39). PE might also play a role in hepatic lipoprotein secretion, because nascent, intracellular very low density lipoproteins that move through the secretory pathway are highly enriched in PE compared with the lipoproteins that are secreted from hepatocytes (40,41).…”