Extracellular concentration of homocysteine in human cell lines is influenced by specific inhibitors of cyst(e)ine transport.
Despite the growing evidence that plasma homocysteine is a cardiovascular risk factor, the mechanism behind the vascular injuries is still unknown. Studies of the cellular uptake systems for homocysteine are scarce, but membrane transporters of cyst(e)ine seem to be involved. In the present study the cellular uptake of extracellular homocysteine in HeLa and hepatoma cell lines is investigated by using several different transport inhibitors for cellular uptake of cyst(e)ine. It is shown that systems A and Xc- are the main transport systems for homocysteine uptake in HeLa cells. It is also confirmed that the magnitude of homocysteine uptake in hepatoma cells is lower than in HeLa cells. However, in the presence of high amounts of extracellular homocysteine both cell types exhibited a high elimination of homocysteine, which was inhibited by the presence of inhibitors of systems A or Xc-. It is possible that there is normally a high turnover of homocysteine in cell cultures, which is not detected by occasional determinations of homocysteine concentrations. The complex pattern of homocysteine production, release, uptake and distribution between different cells in the body is important to examine further in order to possibly be able to modulate the elimination of homocysteine from circulation and thereby lower the risk of cardiovascular disease.
Hultberg
Björn
B
Institute of Laboratory Medicine, Department of Clinical Chemistry, University Hospital, Lund, Sweden. bjorn.hultberg@klinkem.lu.se
D026905:Amino Acid Transport Systems / Q000037:antagonists & inhibitors*; D001692:Biological Transport; D006528:Carcinoma, Hepatocellular / Q000378:metabolism*; D003545:Cysteine / Q000378:metabolism*; D045604:Extracellular Fluid / Q000737:chemistry*; D006367:HeLa Cells; D006710:Homocysteine / Q000378:metabolism*; D006801:Humans; D008113:Liver Neoplasms / Q000378:metabolism*; D014407:Tumor Cells, Cultured
D026905:Amino Acid Transport Systems; D006710:Homocysteine; D003545:Cysteine