Brain γ-glutamyl cysteine synthetase (GCS) mRNA expression patterns correlate with regional-specific enzyme activities and glutathione levels

Abstract

The first and rate-limiting reaction in the formation of glutathione is catalyzed by gamma-glutamylcysteine synthetase (GCS), a dimer composed of a catalytic heavy and a regulatory light subunit. We previously found that heavy subunit GCS mRNA appears to be expressed at high levels in the hippocampus, cerebellum, and cortex of murine brain and at lower levels in the neostriatum (Kang et al. [1997] NeuroReport 8:2053). Here we report that variations in expression of light subunit GCS mRNA in murine brain resembles that of the heavy subunit mRNA with a few minor exceptions. Moreover, levels of GCS activity and glutathione levels in various brain regions appear to correspond to levels of expression of both GCS mRNA subunits. Based on these data, differences in the distribution of expression of the GCS subunits in the brain may therefore have major implications for the susceptibility of various brain regions to oxidative stress and/or mitochondrial damage.