Changes in the expression of cytochrome P450 genes in hemin-induced differentiated K562 cells

Fusako Nagai, Mikiko Shimizu, Tomoko Sakamoto, Takeshi Kobayashi, Hiroomi Tamura

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

We have previously reported the expression of CYP genes in human myeloblastic and lymphoid cell lines, and the induction of the CYP3A4 and GSTP1 genes by oxidative stress in the human erythroleukemia cell line, K562. To further elucidate the role of drug metabolizing enzymes in hematogenesis, we have characterized the expression of CYP genes in hemin-induced differentiated K562 cells. After incubation with 50 μM hemin for 3 d, the expression of CYP1A1 and CYP3A4 genes was induced by 2.5- and 3.5-fold, respectively. In contrast, the CYP1B1 and CYP2E1 genes were downregulated in these cells to below 10% of the control levels. Moreover, these changes correlated with the hemin dose and culture time. Metabolism of midazolam, a probe substrate for CYP3A4, in the differentiated K562 cells increased by 2-folds, suggesting that the induction of CYP3A4 activity is consistent with the mRNA level. If these changes in the CYP expression profile in hematopoietic cells occurred, the susceptibility to xenobiotics and/or the therapeutic drugs of the cells might be influenced, and it also affects the metabolism of endogenous substrates, such as steroids and prostaglandins.

Original languageEnglish
Pages (from-to)1954-1957
Number of pages4
JournalBiological and Pharmaceutical Bulletin
Volume30
Issue number10
DOIs
Publication statusPublished - 2007 Oct

Fingerprint

Cytochrome P-450 CYP3A
Hemin
K562 Cells
Cytochrome P-450 Enzyme System
Genes
Gene Expression
Cell Line
Cytochrome P-450 CYP2E1
Leukemia, Erythroblastic, Acute
Cytochrome P-450 CYP1A1
Midazolam
Xenobiotics
Pharmaceutical Preparations
Prostaglandins
Oxidative Stress
Down-Regulation
Steroids
Lymphocytes
Messenger RNA
Enzymes

Keywords

  • Cytochrome P450
  • Differentiation
  • K562 cell

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology, Toxicology and Pharmaceutics(all)

Cite this

Changes in the expression of cytochrome P450 genes in hemin-induced differentiated K562 cells. / Nagai, Fusako; Shimizu, Mikiko; Sakamoto, Tomoko; Kobayashi, Takeshi; Tamura, Hiroomi.

In: Biological and Pharmaceutical Bulletin, Vol. 30, No. 10, 10.2007, p. 1954-1957.

Research output: Contribution to journalArticle

Nagai, Fusako ; Shimizu, Mikiko ; Sakamoto, Tomoko ; Kobayashi, Takeshi ; Tamura, Hiroomi. / Changes in the expression of cytochrome P450 genes in hemin-induced differentiated K562 cells. In: Biological and Pharmaceutical Bulletin. 2007 ; Vol. 30, No. 10. pp. 1954-1957.
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