Formation of acetaldehyde adducts of glutathione S-transferase A3 in the liver of rats administered alcohol chronically

Sultana, Rukhsana; Raju, Bhupanapadu Sunkesula Solomon; Sharma, Varsha; Reddanna, Pallu; Babu, Phanithi Prakash

doi:10.1016/j.alcohol.2004.12.004

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Volume 35, Issue 1 , Pages 57-66, January 2005

Formation of acetaldehyde adducts of glutathione S-transferase A3 in the liver of rats administered alcohol chronically

Rukhsana Sultana
- Department of Animal Sciences, School of Life Sciences, University of Hyderabad, Hyderabad - 500 046, India
- Present address: Department of Chemistry, University of Kentucky, Lexington, KY 40506, USA.
Bhupanapadu Sunkesula Solomon Raju
- Department of Animal Sciences, School of Life Sciences, University of Hyderabad, Hyderabad - 500 046, India
Varsha Sharma
- School of Life Sciences, Jawaharlal Nehru University, New Delhi 110067
Pallu Reddanna
- Department of Animal Sciences, School of Life Sciences, University of Hyderabad, Hyderabad - 500 046, India
Phanithi Prakash Babu
- Department of Animal Sciences, School of Life Sciences, University of Hyderabad, Hyderabad - 500 046, India
- Corresponding author. Tel.: +91-40-23134584; fax: +91-40-23010145/23010120.

Received 23 April 2004; received in revised form 26 November 2004; accepted 4 December 2004.

Accepting Editor: T.R. Jerrells

Abstract

Hepatic tissue damage induced by chronic exposure to alcohol is mediated through acetaldehyde and associated with reactive oxygen species, which impair cellular defense mechanisms. Because glutathione S-transferases (GSTs) play an important role in the detoxification of xenobiotics and reactive oxygen species, the current study was undertaken to test the effect of alcohol administration on structural and functional characteristics of rat (r) liver Alpha class rGSTs. Western blot analysis revealed an appreciable change in the expression of rGSTA3 subunit levels, whereas no change was observed in activity after chronic alcohol treatment. Reverse-phase high performance liquid chromatographic analysis of rat liver GSTs that were affinity purified with glutathione showed a 1.07-fold increase in rGSTA3 subunit levels in rats treated with alcohol chronically. In addition, liquid chromatographic–electrospray ionization mass spectrometric analysis of GSTs that were affinity purified with glutathione showed the formation of acetaldehyde adducts to the rGSTA3 subunit. Given the abundant expression of rGSTA3 subunit and acetaldehyde adduct formation, results of the current study support the suggestion that modification of rGSTA3 subunit, and thus its impaired function, in alcohol-exposed rats may contribute to the progression of alcohol-induced liver damage.

Keywords: Alcohol, Liver, Glutathione S-transferase, Acetaldehyde, Electrospray ionization mass spectrometry