Pyruvate kinase synthesis and degradation by normal and pathologic cells during erythroid maturation.
Mature erythrocytes contain a specific isozyme of pyruvate kinase (R-PK) while immature erythroblasts coexpress R-PK and another isozyme, M2-PK. To determine what roles degradation and decreasing of synthesis played in the disappearance of M2-PK during erythroid maturation, M2-PK and R-PK synthesis and degradation were studied in erythroblasts from fetal liver and blood BFU-E-derived erythroblasts from healthy subjects, an erythroleukemic patient, and a patient with an erythrocyte PK hyperactivity associated with M2-PK persistence in mature erythrocytes. In normal erythroblasts, R-PK synthesis was constant throughout erythroid maturation, whereas M2-PK synthesis decreased to the point of becoming undetectable. R-PK degradation was very low, while M2-PK degradation was more pronounced and steady during erythroid maturation. In leukemic erythroblasts, total protein turnover was higher than in normal cells, but the M2-PK degradation rate was lower. In erythroblasts from the patient with M2-PK persistence in mature erythrocytes, M2-PK synthesis did not decline with cell maturation. In conclusion, our results emphasize the importance of the decrease of M2-PK synthesis in the disappearance of M2-PK during erythroid maturation. Further studies of patients with pathologic persistence of M2-PK synthesis will help in the understanding of this event involved in erythroid maturation.
Max-Audit
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I
INSERM U91 Hôpital Henri Mondor, Créteil, France.
Kechemir
D
D
Mitjavila
M T
MT
Vainchenker
W
W
Rotten
D
D
Rosa
R
R
D000328:Adult; D000939:Epitopes / Q000032:analysis; D004900:Erythroblasts / Q000201:enzymology* / Q000378:metabolism / Q000473:pathology; D004920:Erythropoiesis; D005333:Fetus; D006801:Humans; D007527:Isoenzymes / Q000096:biosynthesis / Q000097:blood / Q000302:isolation & purification; D004915:Leukemia, Erythroblastic, Acute / Q000097:blood / Q000201:enzymology / Q000473:pathology; D008099:Liver / Q000201:enzymology; D011233:Precipitin Tests; D011770:Pyruvate Kinase / Q000096:biosynthesis* / Q000097:blood / Q000302:isolation & purification
D000939:Epitopes; D007527:Isoenzymes; D011770:Pyruvate Kinase