Secretion of a nonspecific lipid transfer protein by hepatoma cells in culture.
Nonspecific lipid transfer protein (sterol carrier protein2) has previously been proposed to function as (i) a catalyst for intracellular movement of newly synthesized phospholipid, (ii) a cofactor in the biosynthesis and metabolism of cholesterol, and (iii) a cofactor in the feedback inhibition of cholesterol synthesis. Each of these functions is based upon the premise that nonspecific lipid transfer protein (nsLTP) is cytosolic. However, evidence presented in this report suggests that, at least in the case of cultured hepatoma cells, nsLTP is secreted. This conclusion is supported by three observations. First, after culture of hepatoma cells for 10 h, 88% of the nsLTP (as judged by its phosphatidylethanolamine transfer activity) appears in the medium, whereas the cytosolic level of transfer activity remains unchanged. Furthermore, this is accompanied by the appearance in the medium of a polypeptide of Mr 12,200-12,500, which corresponds to the known molecular weight of nsLTP. Finally, it was observed that the appearance of both the activity and the polypeptide in the medium are inhibited by monensin, an inhibitor of secretion. Thus their appearance seems to represent secretion and not simply leakage from the cells. Further evidence that nsLTP does not play an important role in the cytosolic transport of phospholipid and sterol is provided by our observation that hepatoma cells containing a level of nsLTP only 10-15% of that found in liver nevertheless possess near-normal membrane phospholipid compositions and retain the ability to feedback-inhibit cholesterol biosynthesis.
D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D002352:Carrier Proteins / Q000378:metabolism*; D002460:Cell Line; D003470:Culture Media; D005110:Extracellular Space / Q000378:metabolism; D050356:Lipid Metabolism; D008114:Liver Neoplasms, Experimental / Q000378:metabolism*; D008985:Monensin / Q000494:pharmacology; D010713:Phosphatidylcholines / Q000378:metabolism; D010714:Phosphatidylethanolamines / Q000378:metabolism; D010940:Plant Proteins; D051381:Rats
D002352:Carrier Proteins; D003470:Culture Media; D010713:Phosphatidylcholines; D010714:Phosphatidylethanolamines; D010940:Plant Proteins; C072087:sterol carrier proteins; D008985:Monensin