Format

Send to

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

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

Author information

1
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

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.

PMID:
19769485
PMCID:
PMC2864655
DOI:
10.1089/ars.2009.2883
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Atypon Icon for PubMed Central
Loading ...
Support Center