Constitutive mRNA expression of various glutathione S-transferase isoforms in different tissues of mice

Tamara Raphael Knight1, Supratim Choudhuri, Curtis D Klaassen

  • 1Department of Pharmacology, Toxicology, and Therapeutics, University of Kansas Medical Center, Kansas City, KS 66160, USA.

Insights

Glutathione S-transferase (Gst) enzymes protect cells from oxidative stress and metabolize toxins. This study mapped Gst mRNA expression in 14 mouse tissues, revealing varied isoform distribution and significant gender-based differences, particularly in kidneys and gonads.

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Toxicology

Background:

  • Glutathione S-transferase (Gst) enzymes are crucial for cellular defense against electrophiles and oxidative stress products.
  • Their role in metabolizing xenobiotics, including drugs and carcinogens, makes their expression patterns vital for pharmacology and toxicology.
  • Constitutive Gst expression levels can indicate tissue-specific chemical stress resilience.

Purpose of the Study:

  • To investigate the constitutive mRNA expression of 19 distinct Gst enzyme isoforms across 14 different mouse tissues.
  • To identify general principles governing Gst isoform distribution and expression levels in various organs.
  • To explore potential gender-specific differences in Gst expression patterns.

Main Methods:

  • Quantitative analysis of mRNA expression levels for 19 Gst isoforms.
  • Examination of tissue samples from 14 distinct organs in mice.
  • Comparative analysis of Gst expression between male and female mice.

Main Results:

  • Multiple Gst isoforms were constitutively expressed in all examined tissues.
  • Gstk1, Gstm1, Gstm4, Gstm6, and Gstt1 were broadly expressed across most tissues.
  • Significant gender differences in Gst expression were observed, with higher levels in females for kidney, heart, and gonads. Notably, the stomach exhibited high expression of at least eight Gst isoforms, contrasting with typical GI tract expression patterns.

Conclusions:

  • Gst isoforms show diverse tissue-specific expression patterns in mice.
  • The high expression of numerous Gst isoforms in the gastrointestinal tract and liver underscores their significant role in detoxifying ingested xenobiotics.
  • Gender significantly influences Gst isoform expression, suggesting differential susceptibility or metabolic capacity between sexes.