Effect of serum proteins on haem uptake and metabolism in primary cultures of liver cells.
A role of haemopexin in transporting haem to hepatocytes for degradation has been inferred from the high affinity of haemopexin for haem. We have examined this question in primary cultures of chick-embryo and adult rat liver cells. We present here the results of four sets of experiments which indicate that haemopexin retarded haem uptake by hepatocytes in culture. (1) Haem bound to bovine serum albumin is known to repress the activity of delta-aminolaevulinate synthase in chick cultures as indicated by decreased porphyrin accumulation. When haem-albumin was added in the presence of excess purified or freshly secreted chicken haemopexin, no haem-mediated repression of porphyrin production was observed. The haem-mediated repression of porphyrin accumulation was partially prevented when human, but not chicken, albumin was added to cultures. This finding reflected the higher affinity of human albumin for haem compared with that of chicken albumin. (2) Haemopexin inhibited the ability of haem to be incorporated into cytochrome P-450 induced in the chick cultures in the presence of the iron chelator desferrioxamine. (3) The rate of association of [55Fe]haem with cultured rat hepatocytes when [55Fe]haem-haemopexin was added was one-eighth of the rate observed when [55Fe]haem-bovine serum albumin was used as the haem donor. (4) The presence of haemopexin also diminished the catabolism of haem by both rat and chick-embryo liver cell cultures. It is concluded that the uptake and subsequent metabolic effects of haem are inhibited in cultured hepatocytes by proteins such as haemopexin which have a high affinity for haem.
Sinclair
P R
PR
Veterans Administration Medical Centre, White River Junction, VT 05001.
Bement
W J
WJ
Gorman
N
N
Liem
H H
HH
Wolkoff
A W
AW
Muller-Eberhard
U
U
D000624:5-Aminolevulinate Synthetase / Q000378:metabolism; D000818:Animals; D002478:Cells, Cultured; D002642:Chick Embryo; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D006418:Heme / Q000378:metabolism* / Q000493:pharmacokinetics; D006466:Hemopexin / Q000494:pharmacology*; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D046911:Macromolecular Substances; D008297:Male; D011166:Porphyrins / Q000096:biosynthesis; D051381:Rats; D011919:Rats, Inbred Strains; D012709:Serum Albumin / Q000494:pharmacology
D046911:Macromolecular Substances; D011166:Porphyrins; D012709:Serum Albumin; D006418:Heme; D006466:Hemopexin; D003577:Cytochrome P-450 Enzyme System; D000624:5-Aminolevulinate Synthetase