Hemoglobin content is increased in the human erythroleukemia K562 cell line by a 56.2-kD peptide from uremic plasma.
BACKGROUND
Some abnormalities in porphyrin metabolism have been described in erythrocytes from patients with end-stage renal failure. A peptidic fraction of 56.2 kD isolated from plasma of these patients was previously identified as an aminolevulinate dehydratase inhibitor. The aim of this study was to examine the in vitro effect of this peptide on heme synthesis in the erythroleukemia K562 cells.


METHODS
The 56.2-kD fraction was purified from uremic plasma by protein electroelution and, its action on the mitochondrial rate-limiting steps of heme synthesis, as well as the hemoglobin content during erythroid differentiation induced by sodium butyrate, was investigated in K562 cells.


RESULTS
Two hours after addition of the 56.2-kD peptide, the activities of aminolevulinate acid synthase and aminolevulinate dehydratase were reduced while the activity of the ferrochelatase was enhanced, indicating that this peptide easily across the membranes. A 3-day incubation with this peptide enhanced approximately twofold the hemoglobin and porphyrin levels during erythroid differentiation of K562 cells without variation of cell growth.


CONCLUSIONS
This study shows that the addition of the 56.2-kD uremic factor to K562 cells was clearly implicated in heme disturbances existing in chronic renal failure but it did not play a negative role in the pathogenesis of the uremic anemia.
Fontanellas
Antonio
A
Centro de Investigación, Hospital 12 de Octubre, Madrid, Spain.
Navarro-Ordoñez
Susana
S
Morán-Jiménez
María-José
MJ
Guolo
Marcelo
M
Franco
Carlos
C
García-Bravo
María
M
Pataro
Luis
L
Batlle
Alcira
A
de Salamanca
Rafael Enríquez
RE
D002478:Cells, Cultured; D004912:Erythrocytes / Q000201:enzymology; D006454:Hemoglobins / Q000032:analysis*; D006801:Humans; D020014:K562 Cells / Q000737:chemistry; D007676:Kidney Failure, Chronic / Q000097:blood*; D010455:Peptides / Q000097:blood*; D000623:Porphobilinogen Synthase / Q000037:antagonists & inhibitors / Q000502:physiology; D014511:Uremia / Q000097:blood*
D006454:Hemoglobins; D010455:Peptides; D000623:Porphobilinogen Synthase