Expression of coproporphyrinogen oxidase and synthesis of hemoglobin in human erythroleukemia K562 cells
2001
Taketani, Shigeru | Furukawa, Takako | Furuyama, Kazumichi
Coproporphyrinogen oxidase (CPOX), the sixth enzyme in the hemeâbiosynthetic pathway, catalyzes oxidative decarboxylation of coproporphyrinogen to protoporphyrinogen and is located in the intermembrane space of mitochondria. To clarify the importance of CPOX in the regulation of heme biosynthesis in erythroid cells, we established human erythroleukemia K562 cells stably expressing mouse CPOX. The CPOX cDNAâtransfected cells had sevenfold higher CPOX activity than cells transfected with vector only. Expression of ferrochelatase and heme content in the transfected cells increased slightly compared with the control. When K562 cells overexpressing CPOX were treated with δâaminolevulinic acid (ALA), most became benzidineâpositive without induction of the expression of CPOX or ferrochelatase, and the heme content was about twofold higher than that in ALAâtreated control cells. Increases in cellular heme concomitant with a marked induction of the expression of hemeâbiosynthetic enzymes, including CPOX, ferrochelatase and erythroidâspecific δâaminolevulinic acid synthase, as well as of αâglobin synthesis, were observed when cells were treated with transforming growth factor (TGF)β1. These increases in the transfected cells were twice those in control cells, indicating that overexpression of CPOX enhanced induction of the differentiation of K562 cells mediated by TGFβ1 or ALA. Conversely, the transfection of antisense oligonucleotide to human CPOX mRNA into untreated and TGFβ1âtreated K562 cells led to a decrease in heme production compared with sense oligonucleotideâtransfected cells. These results suggest that CPOX plays an important role in the regulation of heme biosynthesis during erythroid differentiation.
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