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Selenoprotein H is a recently identified member of the selenoprotein family whose function is not fully known. Previous studies from our laboratory and others showed that Drosophila melanogaster selenoprotein H is essential for viability and antioxidant defense. In this study we investigated the function of human selenoprotein H in murine hippocampal HT22 cells engineered to stably overexpress the protein. After treatment of cells with L-buthionine-(S,R)-sulfoximine to deplete glutathione, selenoprotein H-overexpressing cells exhibited higher levels of total glutathione, total antioxidant capacities, and glutathione peroxidase enzymatic activity than did vector control cells. Overexpression of selenoprotein H also up-regulated the mRNA levels of endogenous selenoprotein H, glutamylcysteine synthetase heavy and light chains, and glutathione S-transferases Alpha 2, Alpha 4, and Omega 1. The amino acid sequence of selenoprotein H contains four putative nuclear localization sequences and an AT-hook motif, a small DNA-binding domain first identified in high mobility group proteins. Chromatin immunoprecipitation using a green fluorescent protein-selenoprotein H fusion revealed binding to sequences containing heat shock and/or stress response elements. Thus, selenoprotein H is a redox-responsive DNA-binding protein of the AT-hook family and functions in regulating expression levels of genes involved in de novo glutathione synthesis and phase II detoxification in response to redox status.Selenium has long been known for its antioxidant properties, and accumulated evidence indicates that many of the beneficial effects of this trace element in our diet are attributable to selenoenzymes. The functions of selenoenzymes include protecting cell membranes, proteins, and nucleic acids from cumulative oxidative damage and maintaining cellular redox balance. Selenium is highly retained in neuronal tissue during selenium deficiency (1), and the functions of selenoproteins in the brain are highlighted by the development of neurological defects in mice that underwent targeted disruption of selenoprotein P, a selenium transport protein whose functions may also include antioxidant defense and heavy metal chelation (2, 3). To date, 25 selenoprotein genes have been identified in the human genome (4), but the functions of many of them are yet to be fully defined. Selenoprotein H (SelH) 3 was initially identified in the Drosophila melanogaster genome and subsequently in the human and mouse genomes, where expression is high in the brain. In previous studies we and others showed that D. melanogaster SelH is required for viability, and overexpression of the protein increased antioxidant capacity in Drosophila embryo-derived Schneider S2 cells when exposed to homocysteic acid-induced GSH depletion (5, 6).Two recent studies have begun to investigate the functions of human SelH. We reported that overexpression of human SelH protects against UV-induced cell death via a decrease in superoxide levels (7). A study employing bioinformatic analysis a...

Comprehensive and accurate characterization of brain metabolome is fundamental to brain science, but has been hindered by technical limitations. We profiled the brain metabolome in male Wistar rats at different ages (day 1 to week 111) using high-sensitivity and high-resolution mass spectrometry. Totally 380 metabolites were identified and 232 of them were quantitated. Compared with anatomical regions, age had a greater effect on variations in the brain metabolome. Lipids, fatty acids and amino acids accounted for the largest proportions of the brain metabolome, and their concentrations varied across the lifespan. The levels of polyunsaturated fatty acids were higher in infancy (week 1 to week 3) compared with later ages, and the ratio of omega-6 to omega-3 fatty acids increased in the aged brain (week 56 to week 111). Importantly, a panel of 20 bile acids were quantitatively measured, most of which have not previously been documented in the brain metabolome. This study extends the breadth of the mammalian brain metabolome as well as our knowledge of functional brain development, both of which are critically important to move the brain science forward.