Glutathione S-transferases and thiol concentrations in embryonic and early fetal tissues

Abstract

Background: Glutathione S-transferases (GSTs) are important in intracellular binding and transport of numerous compounds, and play a central role in human detoxification processes. Human GSTs mainly consist of class Pi (GSTP), Mu (GSTM), Alpha (GSTA) and Theta (GSTT) enzymes, each subdivided into one or more isoenzymes. They catalyse the conjugation of glutathione (GSH) to toxic compounds, resulting in more water-soluble and less biologically active products that may be easily excreted. The reactive -SH group in GSH is provided by cysteine, an important amino acid in GSH synthesis.

Methods: GST expression, enzyme activity and concentrations of cysteine and GSH in cytosolic fractions of organs from an embryo and a fetus at 8 and 13 weeks gestational age respectively were investigated.

Results: GSTP1 was predominantly present in all tissues of both the embryo and fetus. GSTA (GSTA1 + GSTA2) concentrations were moderate as compared with GSTP1, whereas GSTM1 was present in only low amounts. GSTT1 was not detected in any tissue. GST activity was highest in organs exposed directly to amniotic fluid. In all embryonic and fetal organs, considerable amounts of GSH and cysteine were detected, with higher GSH concentrations in organs where lower cysteine concentrations were demonstrated.

Conclusions: These results suggest that in embryonic and early fetal development cysteine, GSH and GSTs are present in high amounts, and that GSTP1 is the most important GST isoform at these developmental stages.