The effects of changes in glutathione levels through exogenous agents on intracellular cysteine content and protein adduct formation in chronic alcohol-treated VL17A cells

S. Mathan Kumar, Madhumitha Haridoss, Kavitha Swaminathan, Ramesh Kumar Gopal, Dahn Clemens, Aparajita Dey

Research output: Contribution to journalArticle

3 Scopus citations

Abstract

Alcohol-mediated liver injury is associated with changes in the level of the major cellular antioxidant glutathione (GSH). It is interesting to investigate if the changes in intracellular GSH level through exogenous agents affect the intracellular cysteine content and the protein adduct formation indicative of oxidative insult in chronic alcohol treated liver cells. In VL-17A cells treated with 2 mM N-acetyl cysteine (NAC) or 0.1 mM ursodeoxycholic acid (UDCA) plus 100 mM ethanol, an increase in cysteine concentration which was accompanied by decreases in hydroxynonenal (HNE) and glutathionylated protein adducts were observed. Pretreatment of 100 mM ethanol treated VL-17A cells with 0.4 mM buthionine sulfoximine (BSO) or 1 mM diethyl maleate (DEM) had opposite effects. Thus, altered GSH level through exogenous agents may either potentiate or ameliorate chronic alcohol-mediated protein adduct formation and change the cysteine level in chronic alcohol treated VL-17A cells. The gene expression of non-treated and ethanol-treated hepatocytes in 2 microarray datasets was also compared to locate differentially expressed genes involved in cysteine metabolism. The study demonstrates that increased protein adducts formation and changes in cysteine concentration occur under chronic alcohol condition in liver cells which may increase alcohol-mediated oxidative injury.

Original languageEnglish (US)
Pages (from-to)128-135
Number of pages8
JournalToxicology Mechanisms and Methods
Volume27
Issue number2
DOIs
StatePublished - Feb 12 2017

Keywords

  • Alcohol
  • CYP2E1
  • GSH
  • intracellular cysteine
  • oxidative injury

ASJC Scopus subject areas

  • Toxicology
  • Health, Toxicology and Mutagenesis

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