Glutathione level regulates HNE-induced genotoxicity in human erythroleukemia cells

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

Research output: Contribution to journalArticle

44 Citations (Scopus)

Abstract

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
Volume227
Issue number2
DOIs
StatePublished - Mar 1 2008

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Leukemia, Erythroblastic, Acute
Glutathione
DNA Damage
K562 Cells
DNA
Aldehydes
Lipids
4-hydroxy-2-nonenal
2-nonenal
Aldehyde Reductase
Detoxification
Oxidative stress
Comet Assay
Poisons
Ablation
Lipid Peroxidation
Isoenzymes
Assays
Reactive Oxygen Species
Esters

Keywords

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

ASJC Scopus subject areas

  • Pharmacology
  • Toxicology

Cite this

Glutathione level regulates HNE-induced genotoxicity in human erythroleukemia cells. / Yadav, Umesh C S; Ramana, Kota; Awasthi, Yogesh C.; Srivastava, Satish.

In: Toxicology and Applied Pharmacology, Vol. 227, No. 2, 01.03.2008, p. 257-264.

Research output: Contribution to journalArticle

Yadav, Umesh C S ; Ramana, Kota ; Awasthi, Yogesh C. ; Srivastava, Satish. / Glutathione level regulates HNE-induced genotoxicity in human erythroleukemia cells. In: Toxicology and Applied Pharmacology. 2008 ; Vol. 227, No. 2. pp. 257-264.
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