Elevated glutathione level does not protect against chronic alcohol mediated apoptosis in recombinant human hepatoma cell line VL-17A over-expressing alcohol metabolizing enzymes - Alcohol dehydrogenase and Cytochrome P450 2E1

Karthikeyan Chandrasekaran, Kavitha Swaminathan, S. Mathan Kumar, Suvro Chatterjee, Dahn L Clemens, Aparajita Dey

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

Chronic consumption of alcohol leads to liver injury. Ethanol-inducible Cytochrome P450 2E1 (CYP2E1) plays a critical role in alcohol mediated oxidative stress due to its ability to metabolize ethanol. In the present study, using the recombinant human hepatoma cell line VL-17A that over-expresses the alcohol metabolizing enzymes - alcohol dehydrogenase (ADH) and CYP2E1; and control HepG2 cells, the mechanism and mode of cell death due to chronic ethanol exposure were studied. Untreated VL-17A cells exhibited apoptosis and oxidative stress when compared with untreated HepG2 cells. Chronic alcohol exposure, i.e., 100. mM ethanol treatment for 72. h caused a significant decrease in viability (47%) in VL-17A cells but not in HepG2 cells. Chronic ethanol mediated cell death in VL-17A cells was predominantly apoptotic, with increased oxidative stress as the underlying mechanism. Chronic ethanol exposure of VL-17A cells resulted in 1.1- to 2.5-fold increased levels of ADH and CYP2E1. Interestingly, the level of the antioxidant GSH was found to be 3-fold upregulated in VL-17A cells treated with ethanol, which may be a metabolic adaptation to the persistent and over-whelming oxidative stress. In conclusion, the increased GSH level may not be sufficient enough to protect VL-17A cells from chronic alcohol mediated oxidative stress and resultant apoptosis.

Original languageEnglish (US)
Pages (from-to)969-978
Number of pages10
JournalToxicology in Vitro
Volume25
Issue number4
DOIs
StatePublished - Jun 1 2011

Fingerprint

Cytochrome P-450 CYP2E1
Alcohol Dehydrogenase
Glutathione
Oxidative stress
Hepatocellular Carcinoma
Ethanol
Cells
Alcohols
Apoptosis
Cell Line
Oxidative Stress
Enzymes
Hep G2 Cells
Cell death
Cell Death
Aptitude
Alcohol Drinking
Liver
Antioxidants
Wounds and Injuries

Keywords

  • ADH
  • Apoptosis
  • CYP2E1
  • Chronic alcohol
  • GSH
  • Liver

ASJC Scopus subject areas

  • Toxicology

Cite this

Elevated glutathione level does not protect against chronic alcohol mediated apoptosis in recombinant human hepatoma cell line VL-17A over-expressing alcohol metabolizing enzymes - Alcohol dehydrogenase and Cytochrome P450 2E1. / Chandrasekaran, Karthikeyan; Swaminathan, Kavitha; Kumar, S. Mathan; Chatterjee, Suvro; Clemens, Dahn L; Dey, Aparajita.

In: Toxicology in Vitro, Vol. 25, No. 4, 01.06.2011, p. 969-978.

Research output: Contribution to journalArticle

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abstract = "Chronic consumption of alcohol leads to liver injury. Ethanol-inducible Cytochrome P450 2E1 (CYP2E1) plays a critical role in alcohol mediated oxidative stress due to its ability to metabolize ethanol. In the present study, using the recombinant human hepatoma cell line VL-17A that over-expresses the alcohol metabolizing enzymes - alcohol dehydrogenase (ADH) and CYP2E1; and control HepG2 cells, the mechanism and mode of cell death due to chronic ethanol exposure were studied. Untreated VL-17A cells exhibited apoptosis and oxidative stress when compared with untreated HepG2 cells. Chronic alcohol exposure, i.e., 100. mM ethanol treatment for 72. h caused a significant decrease in viability (47{\%}) in VL-17A cells but not in HepG2 cells. Chronic ethanol mediated cell death in VL-17A cells was predominantly apoptotic, with increased oxidative stress as the underlying mechanism. Chronic ethanol exposure of VL-17A cells resulted in 1.1- to 2.5-fold increased levels of ADH and CYP2E1. Interestingly, the level of the antioxidant GSH was found to be 3-fold upregulated in VL-17A cells treated with ethanol, which may be a metabolic adaptation to the persistent and over-whelming oxidative stress. In conclusion, the increased GSH level may not be sufficient enough to protect VL-17A cells from chronic alcohol mediated oxidative stress and resultant apoptosis.",
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