Relationship between radiosensitivity and Nrf2 target gene expression in human hematopoietic stem cells

Kengo Kato, Kenji Takahashi, Satoru Monzen, Hiroyuki Yamamoto, Atsushi Maruyama, Ken Itoh, Ikuo Kashiwakura

Research output: Contribution to journalArticlepeer-review

28 Citations (Scopus)

Abstract

NFE2-related factor 2 (Nrf2), which belongs to the cap "n" collar family of basic region leucine zipper transcription factors, is a key protein in the coordinated transcriptional induction of expression of various antioxidant genes. The purpose of this study was to analyze the expression of Nrf2 target genes, such as heme oxygenase 1 (HO-1), ferritin heavy polypeptide 1 (FTH1), NAD(P)H dehydrogenase, quinone 1 (NQO1), glutamate-cysteine ligase catalytic subunit, glutamate-cysteine ligase modifier subunit, glutathione reductase (GSR) and thioredoxin reductase 1 (TXNRD1), after X irradiation of CD34 cells that were prepared from human placental/umbilical cord blood hematopoietic stem cells (HSCs). We evaluated the relationship between radiosensitivity and expression of Nrf2 target genes in HSCs. The number of colony-forming cells derived from 2-Gy-irradiated HSCs decreased to approximately 20 of the nonirradiated control. At the same time, the mRNA expression of HO-1, FTH1, NQO1, GSR and TXNRD1 was significantly increased after X irradiation. A statistically significant negative correlation was observed between the surviving fraction of HSCs and the intrinsic NQO1 mRNA expression, indicating that HSCs in which NQO1 mRNA levels are low may also be radioresistant. The present results suggest that the antioxidant system associated with Nrf2 is involved in the radiosensitivity of HSCs.

Original languageEnglish
Pages (from-to)177-184
Number of pages8
JournalRadiation Research
Volume174
Issue number2
DOIs
Publication statusPublished - Aug 2010
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Radiation
  • Biophysics
  • Radiology Nuclear Medicine and imaging

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