Expression patterns and novel splicing variants of glutathione-S-transferase isoenzymes of human lung and hepatocyte cell lines

Cell and Tissue Research
Mario BauerEike Schmuecking

Abstract

Polymorphic glutathione S-transferase (GST) enzymes are involved in the metabolism of xenobiotics. They are of particular interest when studying disease susceptibility and adverse drug responses. The present work deals with the genetic polymorphisms and expression of the five GST classes (alpha, mu, pi, theta and zeta) in human lung and hepatocyte cell lines. We have determined their bioavailability for in vitro approaches. Common genetic polymorphisms of GSTM1 (*0, null), GSTT1 (*0) and GSTP1 (*A/*B, I105V) are detectable. The frequencies of the polymorphisms are within the expected range for a Caucasian population with one exception. The GSTM1*0 allele is 1.5-fold more frequent in lung cell lines. GST mRNAs are frequently but not uniformly distributed among unstimulated in vitro conditions. Lung cell lines show an approximately six-fold higher total GST transcript expression than hepatocyte cell lines. Additional GST transcripts have been identified for GSTT1; they represent alternative new splicing variants that occur in cancerous cell lines and in healthy lung tissue and blood. GST enzyme activity is mainly influenced by GSTP1. The activity promoted by 1-chloro-2,4-dinitrobenzene is significantly correlated to the GSTP1 mRN...Continue Reading

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Citations

Feb 3, 2009·Archives of Toxicology·J G HengstlerH M Bolt
Dec 4, 2012·American Journal of Respiratory and Critical Care Medicine·Aimee HoskinsRyszard Dworski
May 17, 2011·The Journal of Allergy and Clinical Immunology·Kathy T SchroerGurjit K Khurana Hershey
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Jan 17, 2020·Critical Reviews in Toxicology·Patrick E Hanna, M W Anders

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