Protection of hydroquinone-induced apoptosis by downregulation of Fau is mediated by NQO1

E. L. Siew, Chan Kok Meng, G. T. Williams, D. Ross, S. H. Inayat-Hussain

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

The Fau gene (Finkel-Biskis-Reilly murine sarcoma virus (FBR-MuSV)-associated ubiquitously expressed gene) was identified as a potential tumor suppressor gene using a forward genetics approach. Downregulation of Fau by overexpression of its reverse sequence has been shown to inhibit apoptosis induced by DNA-damaging agents. To address a potential role of Fau in benzene toxicity, we investigated the apoptotic effects of hydroquinone (HQ), a major benzene metabolite, in W7.2 mouse thymoma cells transfected with either a plasmid construct expressing the antisense sequence of Fau (rfau) or the empty vector (pcDNA3.1) as a control. HQ induced apoptosis via increased production of reactive oxygen species and DNA damage, measured using dihydroethidine (HE) staining and alkaline Comet assay, respectively, in W7.2 pcDNA3.1 cells. In contrast, when Fau was downregulated by the antisense sequence in W7.2 rfau cells, HQ treatment did not cause DNA damage and oxidative stress and these cells were markedly more resistant to HQ-induced apoptosis. Further investigation revealed that there was an upregulation of NAD(P)H: quinone oxidoreductase 1 (NQO1), a detoxification enzyme for benzene-derived quinones, in W7.2 rfau cells. Compromising cellular NQO1 by use of a specific mechanism-based inhibitor (MAC 220) and NQO1 siRNA resensitized W7.2 rfau cells to HQ-induced apoptosis. Silencing of Fau in W7.2 wild-type cells resulted in increased levels of NQO1, confirming that downregulation of Fau results in NQO1 upregulation which protects against HQ-induced apoptosis.

Original languageEnglish
Pages (from-to)1616-1624
Number of pages9
JournalFree Radical Biology and Medicine
Volume53
Issue number8
DOIs
Publication statusPublished - 15 Oct 2012

Fingerprint

Down-Regulation
Apoptosis
Benzene
Genes
DNA
DNA Damage
Up-Regulation
Murine Sarcoma Viruses
Quinones
Detoxification
Oxidative stress
Metabolites
Comet Assay
Thymoma
Viruses
NAD
Small Interfering RNA
Toxicity
hydroquinone
Tumor Suppressor Genes

Keywords

  • Apoptosis
  • DNA damage
  • Fau
  • Hydroquinone
  • NQO1
  • Oxidative stress

ASJC Scopus subject areas

  • Biochemistry
  • Physiology (medical)

Cite this

Protection of hydroquinone-induced apoptosis by downregulation of Fau is mediated by NQO1. / Siew, E. L.; Kok Meng, Chan; Williams, G. T.; Ross, D.; Inayat-Hussain, S. H.

In: Free Radical Biology and Medicine, Vol. 53, No. 8, 15.10.2012, p. 1616-1624.

Research output: Contribution to journalArticle

Siew, E. L. ; Kok Meng, Chan ; Williams, G. T. ; Ross, D. ; Inayat-Hussain, S. H. / Protection of hydroquinone-induced apoptosis by downregulation of Fau is mediated by NQO1. In: Free Radical Biology and Medicine. 2012 ; Vol. 53, No. 8. pp. 1616-1624.
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