Abstract:
Gamma-glutamylcysteine synthetase (GCS) is the rate limiting enzyme in the synthesis of reduced glutathione (GSH), a major anti-oxidant in cells. Prolonged exposure to mercury as methyl mercury hydroxide (MMH) leads to increased GCS mRNA with accompanying incease in FSH levels. This increase in GSH may represent an adaptive response to mercury. The increases in GCS mRNA can be due to increased stability of the GCS mRNA, GCS gene amplification, or increased transcriptional rate of the GCS gene. Nuclear runon transcription assays did not indicate an increase in transcription rate of the GCS gene in response to MMH. Treatment of animals with actinomycin D did not indicate an increase in the nuclear stability of the GCS transcript in response to MMH as evidenced by an increase in measured mRNA half-life.