Elimination of high amounts of extracellular homocysteine in human cell lines.
BACKGROUND
Many clinical and epidemiological studies show that mild hyperhomocysteinemia is associated with premature vascular disease. Information about the metabolism of homocysteine is therefore essential for an understanding of its role in atherogenesis, thereby enabling a modulation of that risk.


METHODS
In the present study factors influencing the elimination of exogenously added homocysteine in HeLa and hepatoma cell cultures have been investigated with and without inhibition of the transmethylation pathway by adenosine-dialdehyde.


RESULTS
Agents with antioxidative effect (copper chelator and thiols) increased the metabolic removal of extracellular homocysteine in HeLa cell cultures, whereas in hepatoma cell cultures only the thiol N-acetylcysteine increased the elimination. The oxidative agent (copper ions) and cyst(e)ine transport inhibitors decreased the removal in both HeLa and hepatoma cell cultures. The inhibition of the transmethylation pathway by adenosine-dialdehyde increased the removal of exogenously added homocysteine and the addition of the different redox agents and cyst(e)ine transport inhibitors did not specifically influence this increase.


CONCLUSIONS
The elevated removal of exogenously added homocysteine in the presence of adenosine-dialdehyde might be attributed to limited availability of intracellular homocysteine, which leads to a larger amount of extracellular homocysteine being internalized.
Hultberg
Björn
B
Institute of Laboratory Medicine, Department of Clinical Chemistry, University Hospital, S-22185 Lund, Sweden. bjorn.hultberg@klinkem.lu.se
D000241:Adenosine / Q000031:analogs & derivatives / Q000494:pharmacology; D000975:Antioxidants / Q000494:pharmacology; D001161:Arteriosclerosis / Q000209:etiology; D006528:Carcinoma, Hepatocellular / Q000378:metabolism; D045744:Cell Line, Tumor; D006367:HeLa Cells; D006710:Homocysteine / Q000378:metabolism*; D006801:Humans; D020138:Hyperhomocysteinemia / Q000150:complications; D008063:Thioctic Acid / Q000494:pharmacology
D000975:Antioxidants; D006710:Homocysteine; C027579:periodate-oxidized adenosine; D008063:Thioctic Acid; D000241:Adenosine