Expression of coproporphyrinogen oxidase and synthesis of hemoglobin in human erythroleukemia K562 cells

Shigeru Taketani, Takako Furukawa, Kazumichi Furuyama

Research output: Contribution to journalArticlepeer-review

19 Citations (Scopus)

Abstract

Coproporphyrinogen oxidase (CPOX), the sixth enzyme in the heme-biosynthetic 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 cDNA-transfected 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 δ-aminolevulinic acid (ALA), most became benzidine-positive without induction of the expression of CPOX or ferrochelatase, and the heme content was about twofold higher than that in ALA-treated control cells. Increases in cellular heme concomitant with a marked induction of the expression of heme-biosynthetic enzymes, including CPOX, ferrochelatase and erythroid-specific δ-aminolevulinic acid synthase, as well as of α-globin 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 oligo-nucleotide to human CPOX mRNA into untreated and TGFβ1-treated K562 cells led to a decrease in heme production compared with sense oligonucleotide-transfected cells. These results suggest that CPOX plays an important role in the regulation of heme biosynthesis during erythroid differentiation.

Original languageEnglish
Pages (from-to)1705-1711
Number of pages7
JournalEuropean Journal of Biochemistry
Volume268
Issue number6
DOIs
Publication statusPublished - 2001

Keywords

  • Coproporphyrinogen oxidase
  • Erythroid differentiation
  • Heme
  • Hemoglobin
  • Human erythroleukemia K562 cells

ASJC Scopus subject areas

  • Biochemistry

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