Role of Glutathione in the Regulation of Protein Synthesis and Degradation in Eukaryotes

Nonprotein thiols have been postulated as regulators of protein synthesis initiation in eukaryotes. ^{1 , 3} Almost 30 years ago, the classical studies of Zehavi-Willner et al. ⁴ suggested a correlation between glutathione (GSH) oxidation and inhibition of protein synthesis. Indeed, physiological levels of GSH appear to be essential for efficient protein synthesis in many cells. ⁵ Depletion of GSH and/or increase in intracellular levels of glutathione disulfide (GSSG) may lead to inhibition of protein synthesis, ^{5 , 6} Furthermore, by influencing nucleotide biosynthesis ⁷ and through reduction of ribonucleotides, ⁸ GSH metabolism may also play a role in the induction of DNA synthesis. It is known that intracellular GSH levels fluctuate during cell cycle ^{9 , 10} under different culture conditions, and that GSH may be important in the regulation of cellular proliferation. ¹¹ However, it is unknown whether possible changes in DNA synthesis induced by GSH are accompanied by changes in protein synthesis.