Interplay between Selenium Levels, Selenoprotein Expression and Replicative Senescence in WI-38 Human Fibroblasts [Protein Synthesis and Degradation]

January 14th, 2014 by Legrain, Y., Touat-Hamici, Z., Chavatte, L.

Selenium is an essential trace element, which is incorporated as selenocysteine into at least twenty-five selenoproteins using a unique translational UGA-recoding mechanism. Selenoproteins are important enzymes involved in antioxidant defense, redox homeostasis and redox signaling pathways. Selenium levels decline during aging and its deficiency is associated with a marked increase in mortality for people over sixty years. Here, we investigate the relationship between selenium levels in the culture medium, selenoprotein expression and replicative lifespan of human embryonic lung fibroblast WI-38 cells. Selenium levels regulate the entry into replicative senescence and modify the cellular markers characteristic for senescent cells. While selenium supplementation extends the number of population doubling, its deficiency impairs the proliferative capacity of WI-38 cells. We observe that the expression of several selenoproteins involved in antioxidant defense is specifically affected in response to cellular senescence. Their expression is selectively controlled by the modulation of mRNA levels and translational recoding efficiencies. Our data provide novel mechanistic insights into how selenium impacts the replicative lifespan of mammalian cells by identifying several selenoproteins as new targets of senescence.
  • Posted in Journal of Biological Chemistry, Publications
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