Evaluation of carbon tetrachloride-induced stress on rat hepatocytes by 31P NMR and MALDI-TOF mass spectrometry: lysophosphatidylcholine generation from unsaturated phosphatidylcholines.
Carbon tetrachloride (CCl(4)) represents an excellent model to study oxidative injury of cells. It is widely accepted that hepatocellular injury is a consequence of the metabolic conversion of CCl(4) into highly reactive, free radical intermediates. Among the direct toxic effects of CCl(4), stimulation of lipid peroxidation and the binding of the electrophilic radicals to membrane lipids have been suggested to play important roles in the pathogenesis of irreversible cell damage. CCl(4)-induced liver damage was modeled in cultures of rat hepatocytes with the focus on alterations of phosphatidylcholine (PC). The PC acyl chain composition was analyzed by (31)P NMR spectroscopy and MALDI-TOF mass spectrometry. The content of the membrane arachidonoyl PC was decreased by almost 30% after incubation of the cells with CCl(4). This relative decrease was found to correlate with increased concentrations of the corresponding saturated lysophosphatidylcholine (LPC). It is concluded that LPC represents a useful biomarker of CCl(4)-mediated damaging of hepatocytes. It is also speculated that de novo biosynthesis of PC is influenced by CCl(4).
Leibniz Research Centre for Working Environment and Human Factors, Dortmund, Germany.
Alexander
A
Bauer
Anika
A
Schumann
Matthias
M
Gilbert
Christian
C
Wilhelm
Jan G
JG
Hengstler
Jürgen
J
Schiller
Beate
B
Fuchs
D000818:Animals; D002251:Carbon Tetrachloride / Q000633:toxicity; D022781:Hepatocytes / Q000187:drug effects* / Q000378:metabolism; D015227:Lipid Peroxidation; D008244:Lysophosphatidylcholines / Q000378:metabolism*; D009682:Magnetic Resonance Spectroscopy; D018384:Oxidative Stress; D010713:Phosphatidylcholines / Q000378:metabolism*; D010759:Phosphorus Isotopes; D051381:Rats; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
D008244:Lysophosphatidylcholines; D010713:Phosphatidylcholines; D010759:Phosphorus Isotopes; D002251:Carbon Tetrachloride