The neuroprotective functions of selenoprotein M and its role in cytosolic calcium regulation

Antioxid Redox Signal. 2010 Apr 1;12(7):809-18. doi: 10.1089/ars.2009.2883.

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.

MeSH terms

  • Animals
  • Astrocytes / cytology
  • Astrocytes / metabolism
  • Calcium / metabolism*
  • Calcium-Binding Proteins / metabolism
  • Cell Line
  • Cells, Cultured
  • Cytosol / metabolism*
  • Gene Knockdown Techniques
  • Humans
  • Hydrogen Peroxide / metabolism
  • Luminescent Proteins / metabolism
  • Mice
  • Neurons / cytology
  • Neurons / metabolism
  • Neuroprotective Agents / metabolism*
  • Oxidants / metabolism
  • Oxidation-Reduction
  • Oxidative Stress
  • Reactive Oxygen Species / metabolism
  • Selenium / metabolism
  • Selenoproteins / genetics
  • Selenoproteins / metabolism*

Substances

  • Calcium-Binding Proteins
  • Luminescent Proteins
  • Neuroprotective Agents
  • Oxidants
  • Reactive Oxygen Species
  • Selenoproteins
  • Sepm protein, mouse
  • Hydrogen Peroxide
  • Selenium
  • Calcium