Nrf2 controls bone marrow stromal cell susceptibility to oxidative and electrophilic stress

Hong Zhu, Li Zhang, Ken Itoh, Masayuki Yamamoto, David Ross, Michael A. Trush, Jay L. Zweier, Yunbo Li

Research output: Contribution to journalArticle

Abstract

Understanding the molecular pathway(s) controlling the expression of stromal cellular antioxidants and phase 2 enzymes is of importance for developing strategies to protect against bone marrow toxicity induced by oxidants and electrophiles. Accordingly, this study was undertaken to determine the role of the nuclear factor E2-related factor 2 (Nrf2) in regulation of both constitutive and chemoprotectant-inducible expression of antioxidants and phase 2 enzymes in mouse bone marrow stromal cells. The constitutive expression of a series of antioxidants and phase 2 enzymes was significantly lower in stromal cells derived from Nrf2 knockout (Nrf2-/-) mice than those from wild-type littermates (Nrf2+/+). Incubation of Nrf2+/+ stromal cells with 3H-1,2-dithiole-3-thione (D3T) led to a significant induction of various antioxidants and phase 2 enzymes. The inducibility of the above cellular defenses by D3T was abolished in Nrf2-/- cells. As compared to wild-type cells, Nrf2-/- cells were much more susceptible to cytotoxicity induced by reactive oxygen or nitrogen species, 4-hydroxy-2-nonenal, 1,4-hydroquinone, or 1,4-benzoquinone. Upregulation of the antioxidants and phase 2 enzymes by D3T in Nrf2+/+ stromal cells resulted in increased resistance to the above oxidant- and electrophile-induced cytotoxicity, whereas D3T treatment of Nrf2-/- cells only provided a marginal cytoprotection. Taken together, this study demonstrates that Nrf2 is crucial in controlling the expression of bone marrow stromal antioxidants and phase 2 enzymes as well as the susceptibility of these cells to oxidative and electrophilic stress.

Original languageEnglish (US)
Pages (from-to)132-143
Number of pages12
JournalFree Radical Biology and Medicine
Volume41
Issue number1
DOIs
StatePublished - Jul 1 2006

Fingerprint

NF-E2-Related Factor 2
Mesenchymal Stromal Cells
Bone
Oxidative Stress
Antioxidants
Thiones
Enzymes
Stromal Cells
Cytotoxicity
Oxidants
Bone Marrow
Reactive Nitrogen Species
Cytoprotection
Knockout Mice
Toxicity
Reactive Oxygen Species
Up-Regulation

Keywords

  • 3H-1,2-Dithiole-3-thione
  • Antioxidants
  • Bone marrow
  • Cytotoxicity
  • Nrf2
  • Phase 2 enzymes

ASJC Scopus subject areas

  • Medicine(all)
  • Toxicology
  • Clinical Biochemistry

Cite this

Nrf2 controls bone marrow stromal cell susceptibility to oxidative and electrophilic stress. / Zhu, Hong; Zhang, Li; Itoh, Ken; Yamamoto, Masayuki; Ross, David; Trush, Michael A.; Zweier, Jay L.; Li, Yunbo.

In: Free Radical Biology and Medicine, Vol. 41, No. 1, 01.07.2006, p. 132-143.

Research output: Contribution to journalArticle

Zhu, H, Zhang, L, Itoh, K, Yamamoto, M, Ross, D, Trush, MA, Zweier, JL & Li, Y 2006, 'Nrf2 controls bone marrow stromal cell susceptibility to oxidative and electrophilic stress', Free Radical Biology and Medicine, vol. 41, no. 1, pp. 132-143. https://doi.org/10.1016/j.freeradbiomed.2006.03.020
Zhu, Hong ; Zhang, Li ; Itoh, Ken ; Yamamoto, Masayuki ; Ross, David ; Trush, Michael A. ; Zweier, Jay L. ; Li, Yunbo. / Nrf2 controls bone marrow stromal cell susceptibility to oxidative and electrophilic stress. In: Free Radical Biology and Medicine. 2006 ; Vol. 41, No. 1. pp. 132-143.
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