Lysophosphatidates bound to serum albumin activate membrane currents in Xenopus oocytes and neurite retraction in PC12 pheochromocytoma cells.
Serum contains a factor that co-purifies with albumin and causes neurite retraction in PC12 cells, inhibits the proliferation of tumor cells in vitro, and activates the phosphatidylinositol/Ca2+ second messenger system in Xenopus oocytes and other cells. The activity of serum albumin depends on several lysophospholipids bound to albumin. Thin layer chromatographic analysis of the lipids extracted by methanol from serum albumin revealed over a dozen components, several of which evoked oscillatory currents in oocytes. In contrast to serum albumin, most of these lipids were absent in plasma, which lacks the biological activity. The most abundant naturally occurring active component was identified as stearoyl-lysophosphatidic acid. Synthetically prepared lysophosphatidates reproduced the biological activities of the natural serum factor. Adding synthetic lysophosphatidates to inactive fatty acid-free albumin restored activity to the albumin, making the active factor nondialyzable against aqueous solvents and protecting against digestion by various lipases. Since the biologically active lysophosphatidates were produced during blood clotting, in the presence of platelets, and lysophosphatidates have been shown previously to activate platelets, we propose that lysophosphatidates may play an important role in linking platelet activation to receptor-mediated tissue regeneration.
Tigyi
G
G
Department of Psychobiology, University of California, Irvine 92717.
Miledi
R
R
D000818:Animals; D018118:Chloride Channels; D002712:Chlorides / Q000378:metabolism; D002855:Chromatography, Thin Layer; D004268:DNA-Binding Proteins / Q000378:metabolism; D006801:Humans; D007473:Ion Channels / Q000378:metabolism; D008246:Lysophospholipids / Q000378:metabolism*; D008564:Membrane Potentials; D008565:Membrane Proteins / Q000378:metabolism; D016501:Neurites / Q000378:metabolism*; D009687:Nuclear Proteins / Q000378:metabolism; D009865:Oocytes; D016716:PC12 Cells; D015290:Second Messenger Systems; D012709:Serum Albumin / Q000378:metabolism*; D026362:Serum Response Factor; D014407:Tumor Cells, Cultured; D014981:Xenopus
D018118:Chloride Channels; D002712:Chlorides; D004268:DNA-Binding Proteins; D007473:Ion Channels; D008246:Lysophospholipids; D008565:Membrane Proteins; D009687:Nuclear Proteins; D012709:Serum Albumin; D026362:Serum Response Factor