title: The neuroprotective functions of selenoprotein M and its role in cytosolic calcium regulation.
abstract: Selenoproteins contain the trace element selenium incorporated as selenocysteine, the 21st amino acid. Some members of the selenoprotein family, such as the glutathione peroxidases, have well-characterized antioxidant activity, functioning in enzymatic breakdown of hydroperoxides to protect cells against oxidative stress. However, the functions of many of the 25 human selenoproteins, including the brain-enriched selenoprotein M, are unknown. We investigated selenoprotein M function by manipulating expression in murine hippocampal HT22 cells, cerebellar astrocyte C8-D1A cells, and primary neuronal cultures. Overexpression of the protein resulted in a reduction in reactive oxygen species and apoptotic cell death in response to oxidative challenge with hydrogen peroxide. In contrast, knock-down of selenoprotein M using shRNA in primary neuronal cultures caused apoptotic cell death comparable to levels resulting from addition of hydrogen peroxide. Calcium measurements with the indicator cameleon demonstrated that overexpression of selenoprotein M decreased calcium influx in response to hydrogen peroxide. Additionally, knock-down of selenoprotein M expression in cortical cultures caused higher baseline levels of cytosolic calcium than in control cells. These results suggest that selenoprotein M may have an important role in protecting against oxidative damage in the brain and may potentially function in calcium regulation.
authors.affiliation: Department of Cell and Molecular Biology, John A. Burns School of Medicine, University of Hawai'i , 651 Ilalo Street, Honolulu, HI 96813, USA. marci.reeves@gmail.com
authors.forename: Mariclair A
authors.initials: MA
authors.lastname: Reeves
authors.forename: Frederick P
authors.initials: FP
authors.lastname: Bellinger
authors.forename: Marla J
authors.initials: MJ
authors.lastname: Berry
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000166:cytology / Q000378:metabolism; D002118:Calcium / Q000378:metabolism*; D002135:Calcium-Binding Proteins / Q000378:metabolism; D002460:Cell Line; D002478:Cells, Cultured; D003600:Cytosol / Q000378:metabolism*; D055785:Gene Knockdown Techniques; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism; D008164:Luminescent Proteins / Q000378:metabolism; D051379:Mice; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D018696:Neuroprotective Agents / Q000378:metabolism*; D016877:Oxidants / Q000378:metabolism; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D017382:Reactive Oxygen Species / Q000378:metabolism; D012643:Selenium / Q000378:metabolism; D051140:Selenoproteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D002135:Calcium-Binding Proteins; D008164:Luminescent Proteins; D018696:Neuroprotective Agents; D016877:Oxidants; D017382:Reactive Oxygen Species; D051140:Selenoproteins; C499178:Sepm protein, mouse; D006861:Hydrogen Peroxide; D012643:Selenium; D002118:Calcium