Glutathione level regulates HNE-induced genotoxicity in human erythroleukemia cells

Umesh C.S. Yadav, Kota V. Ramana, Yogesh C. Awasthi, Satish K. Srivastava

Research output: Contribution to journalArticlepeer-review

47 Scopus citations


4-Hydroxy-trans-2-nonenal (HNE) is one of the most abundant and toxic lipid aldehydes formed during lipid peroxidation by reactive oxygen species. We have investigated the genotoxic effects of HNE and its regulation by cellular glutathione (GSH) levels in human erythroleukemia (K562) cells. Incubation of K562 cells with HNE (5-10 μM) significantly elicited a 3- to 5-fold increased DNA damage in a time- and dose-dependent manner as measured by comet assay. Depletion of GSH in cells by l-buthionine-[S,R]-sulfoximine (BSO) significantly increased HNE-induced DNA damage, whereas supplementation of GSH by incubating the cells with GSH-ethyl ester significantly decreased HNE-induced genotoxicity. Further, overexpression of mGSTA4-4, a HNE-detoxifying GST isozyme, significantly prevented HNE-induced DNA damage in cells, and ablation of GSTA4-4 and aldose reductase with respective siRNAs further augmented HNE-induced DNA damage. These results suggest that the genotoxicity of HNE is highly dependent on cellular GSH/GST/AR levels and favorable modulation of the aldehyde detoxification system may help in controlling the oxidative stress-induced complications.

Original languageEnglish (US)
Pages (from-to)257-264
Number of pages8
JournalToxicology and Applied Pharmacology
Issue number2
StatePublished - Mar 1 2008
Externally publishedYes


  • Aldose reductase
  • Comet assay
  • DNA damage
  • GSH
  • GST
  • HNE

ASJC Scopus subject areas

  • Toxicology
  • Pharmacology


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