Relationship between oxidative stress and hepatic glutathione levels in ethanol-mediated apoptosis of polarized hepatic cells

Benita L. McVicker, Pamela L. Tuma, Kusum K. Kharbanda, Serene M.L. Lee, Dean J. Tuma

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

Aim: To investigate the role of reactive oxygen species (ROS) in ethanol-mediated cell death of polarized hepatic (WIF-B) cells. Methods: In this work, WIF-B cultures were treated with pyrazole (inducer of cytochrome P4502E1, CYP2E1) and/or L-buthionine sulfoximine (BSO), a known inhibitor of hepatic glutathione (GSH), followed by evaluation of ROS production, antioxidant levels, and measures of cell injury (apoptosis and necrosis). Results: The results revealed that ethanol treatment alone caused a significant two-fold increase in the activation of caspase-3 as well as a similar doubling in ROS. When the activity of the CYP2E1 was increased by pyrazole pretreatment, an additional two-fold elevation in ROS was detected. However, the CYP2E1-related ROS elevation was not accompanied with a correlative increase in apoptotic cell injury, but rather was found to be associated with an increase in necrotic cell death. Interestingly, when the thiol status of the cells was manipulated using BSO, the ethanol-induced activation of caspase-3 was abrogated. Additionally, ethanol-treated cells displayed enhanced susceptibility to Fas-mediated apoptosis that was blocked by GSH depletion as a result of diminished caspase-8 activity. Conclusion: Apoptotic cell death induced as a consequence of ethanol metabolism is not completely dependent upon ROS status but is dependent on sustained GSH levels.

Original languageEnglish (US)
Pages (from-to)2609-2616
Number of pages8
JournalWorld Journal of Gastroenterology
Volume15
Issue number21
DOIs
StatePublished - Jun 7 2009

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Glutathione
Hepatocytes
Reactive Oxygen Species
Oxidative Stress
Ethanol
Apoptosis
Liver
Cytochromes
Buthionine Sulfoximine
Cell Death
Caspase 3
Caspase 8
Wounds and Injuries
Sulfhydryl Compounds
B-Lymphocytes
Necrosis
Antioxidants
pyrazole

Keywords

  • Alcohol
  • Caspase
  • Fas/CD95
  • Glutathione
  • WIF-B cells

ASJC Scopus subject areas

  • Gastroenterology

Cite this

Relationship between oxidative stress and hepatic glutathione levels in ethanol-mediated apoptosis of polarized hepatic cells. / McVicker, Benita L.; Tuma, Pamela L.; Kharbanda, Kusum K.; Lee, Serene M.L.; Tuma, Dean J.

In: World Journal of Gastroenterology, Vol. 15, No. 21, 07.06.2009, p. 2609-2616.

Research output: Contribution to journalArticle

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