O-alkyl-O-methylglycerophosphocholine, an antineoplastic lipid, undergoes spontaneous redistribution between biological membranes prepared from HL-60 cells.
Cytotoxic actions of the unnatural phospholipid 1-O-alkyl-2-O-methyl-sn-glycero-3-phosphocholine (alkylmethyl-GPC) appear to be targeted to the plasma membrane of sensitive cells. We analyzed the distribution of [3H]alkylmethoxy-GPC in subcellular membranes isolated from human promyelocytic leukemia (HL-60) cells. [3H]Alkylmethyl-GPC added to intact cells selectively labels plasma membrane-enriched fractions of the postnuclear supernatant, but the labeling profile is independent of the temperature and duration of the incubation, and concentration of the molecule. Also, an identical distribution pattern is obtained when [3H]alkylmethyl-GPC is directly added to postnuclear supernatants. Moreover, [3H]alkylmethyl-GPC translocates between subcellular membranes in a manner that does not depend on membrane-adsorbed or cytosolic transfer proteins. These results indicate that the subcellular localization studies reported for alkylmethyl-GPC and structurally-related molecules must be interpreted with caution.
Vallari
D S
DS
Medical Sciences Division, Oak Ridge Associated Universities, TN 37831-0117.
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Smith
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Snyder
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D000970:Antineoplastic Agents / Q000378:metabolism*; D002458:Cell Fractionation; D002462:Cell Membrane / Q000378:metabolism*; D002499:Centrifugation, Density Gradient; D003594:Cytoplasmic Granules / Q000378:metabolism / Q000648:ultrastructure; D004721:Endoplasmic Reticulum / Q000378:metabolism / Q000648:ultrastructure; D006056:Golgi Apparatus / Q000378:metabolism / Q000648:ultrastructure; D006801:Humans; D007425:Intracellular Membranes / Q000378:metabolism; D007700:Kinetics; D015473:Leukemia, Promyelocytic, Acute / Q000378:metabolism*; D010742:Phospholipid Ethers / Q000378:metabolism*; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D010742:Phospholipid Ethers; C026659:edelfosine