Overexpression of methionine sulfoxide reductases A and B2 protects MOLT-4 cells against zinc-induced oxidative stress.

Among the amino acids, methionine is the most susceptible to oxidation, and methionine sulfoxide can be catalytically reduced within proteins by methionine sulfoxide reductase A (MsrA) and B (MsrB). As one of the very few repair systems for oxidized proteins, MsrA and MsrB enzymes play a major role in protein homeostasis during aging and have also been involved in cellular defenses against oxidative stress, by scavenging reactive oxygen species. To elucidate the role of zinc on the Msr system, the effects of zinc treatment on control and stably overexpressing MsrA and MsrB2 MOLT-4 leukemia cells have been analyzed. Here we show that zinc treatment has a pro-antioxidant effect in MOLT-4 cells by inducing the transcription of metallothioneins and positively modulating the activity of the Msr enzymes. In contrast, due to its pro-oxidant effect, zinc also led to increased cell death, reactive oxygen species production, and protein damage. Our results indicate that overexpression of the Msr enzymes, due to their antioxidant properties, counteracts the pro-oxidant effects of zinc treatment, which lead to a cellular protection against protein oxidative damage and cell death, by reducing the production of reactive oxygen species.