CHAPTER 28: Selenoprotein H in Neuronal Cells

Selenium exerts its biological effects through selenoproteins in which selenium is incorporated as selenocysteine. Selenoprotein H (SleH) possesses an AT hook that is a DNA-binding protein motif, in addition to its CXXU thioredoxin-like motif that is responsible for redox activity. SelH protects cells from oxidative damage by lowering free-radical accumulation and blocking mitochondria-mediated cell-death pathways. SelH activates mitochondrial biogenesis through modulating PKA–CREB–PGC-1α–NRF1 and Akt–CREB–PGC-1α–NRF1 signaling pathways. Activation of mitochondrial biogenesis by SelH leads to increased mitochondrial mass, proteins and respiration. Selenium also activates mitochondrial biogenesis through the same signaling pathways as in SelH. Furthermore, selenium maintains mitochondrial dynamics by inhibition of mitochondrial fission in glutamate-exposed cells and in the brains of animals subjected to cerebral ischemia.