Lipidomics reveals membrane lipid remodelling and release of potential lipid mediators during early stress responses in a murine melanoma cell line.
Membranes are known to respond rapidly to various environmental perturbations by changing their composition and microdomain organization. In previous work we showed that a membrane fluidizer benzyl alcohol (BA) could mimic the effects of heat stress and enhance heat shock protein synthesis in different mammalian cells. Here we explore heat- and BA-induced stress further by characterizing stress-induced membrane lipid changes in mouse melanoma B16 cells. Lipidomic fingerprints revealed that membrane stress achieved either by heat or BA resulted in pronounced and highly specific alterations in lipid metabolism. The loss in polyenes with the concomitant increase in saturated lipid species was shown to be a consequence of the activation of phopholipases (mainly phopholipase A(2) and C). A phospholipase C-diacylglycerol lipase-monoacylglycerol lipase pathway was identified in B16 cells and contributed significantly to the production of several lipid mediators upon stress including the potent heat shock modulator, arachidonic acid. The accumulation of cholesterol, ceramide and saturated phosphoglyceride species with raft-forming properties observed upon both heat and BA treatments of B16 cells may explain the condensation of ordered plasma membrane domains previously detected by fluorescence microscopy and may serve as a signalling platform in stress responses or as a primary defence mechanism against the noxious effects of stresses.
Balogh
Gábor
G
Institute of Biochemistry, Biological Research Centre, Hungarian Academy of Sciences, Szeged, Hungary.
Péter
Mária
M
Liebisch
Gerhard
G
Horváth
Ibolya
I
Török
Zsolt
Z
Nagy
Eniko
E
Maslyanko
Andriy
A
Benko
Sándor
S
Schmitz
Gerd
G
Harwood
John L
JL
Vígh
László
L
D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism; D019905:Benzyl Alcohol / Q000494:pharmacology*; D002462:Cell Membrane / Q000378:metabolism*; D008401:Gas Chromatography-Mass Spectrometry; D018869:Heat-Shock Response; D008055:Lipids / Q000032:analysis*; D008546:Melanoma, Experimental / Q000378:metabolism*; D008560:Membrane Fluidity / Q000187:drug effects; D008563:Membrane Lipids / Q000378:metabolism*; D021962:Membrane Microdomains / Q000378:metabolism; D051379:Mice; D025341:Principal Component Analysis; D021241:Spectrometry, Mass, Electrospray Ionization; D014407:Tumor Cells, Cultured
D008055:Lipids; D008563:Membrane Lipids; D016718:Arachidonic Acid; D019905:Benzyl Alcohol