Document Detail


Mitochondrial superoxide dismutase SOD2, but not cytosolic SOD1, plays a critical role in protection against glutamate-induced oxidative stress and cell death in HT22 neuronal cells.
MedLine Citation:
PMID:  20060889     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Oxidative cell death is an important contributing factor in neurodegenerative diseases. Using HT22 mouse hippocampal neuronal cells as a model, we sought to demonstrate that mitochondria are crucial early targets of glutamate-induced oxidative cell death. We show that when HT22 cells were transfected with shRNA for knockdown of the mitochondrial superoxide dismutase (SOD2), these cells became more susceptible to glutamate-induced oxidative cell death. The increased susceptibility was accompanied by increased accumulation of mitochondrial superoxide and loss of normal mitochondrial morphology and function at early time points after glutamate exposure. However, overexpression of SOD2 in these cells reduced the mitochondrial superoxide level, protected mitochondrial morphology and functions, and provided resistance against glutamate-induced oxidative cytotoxicity. The change in the sensitivity of these SOD2-altered HT22 cells was neurotoxicant-specific, because the cytotoxicity of hydrogen peroxide was not altered in these cells. In addition, selective knockdown of the cytosolic SOD1 in cultured HT22 cells did not appreciably alter their susceptibility to either glutamate or hydrogen peroxide. These findings show that the mitochondrial SOD2 plays a critical role in protecting neuronal cells from glutamate-induced oxidative stress and cytotoxicity. These data also indicate that mitochondria are important early targets of glutamate-induced oxidative neurotoxicity.
Authors:
Masayuki Fukui; Bao Ting Zhu
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2010-01-11
Journal Detail:
Title:  Free radical biology & medicine     Volume:  48     ISSN:  1873-4596     ISO Abbreviation:  Free Radic. Biol. Med.     Publication Date:  2010 Mar 
Date Detail:
Created Date:  2010-02-17     Completed Date:  2010-06-30     Revised Date:  2014-09-15    
Medline Journal Info:
Nlm Unique ID:  8709159     Medline TA:  Free Radic Biol Med     Country:  United States    
Other Details:
Languages:  eng     Pagination:  821-30     Citation Subset:  IM    
Copyright Information:
Copyright 2010 Elsevier Inc. All rights reserved.
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MeSH Terms
Descriptor/Qualifier:
Animals
Cell Death / drug effects
Cells, Cultured
Glutamic Acid / toxicity
Mice
Mitochondria / enzymology*
Neurons / drug effects,  enzymology,  metabolism*
Oxidative Stress / drug effects
Superoxide Dismutase / metabolism*
Grant Support
ID/Acronym/Agency:
ES15242/ES/NIEHS NIH HHS; P20RR021940/RR/NCRR NIH HHS; R01 ES015242/ES/NIEHS NIH HHS; R01 ES015242-05/ES/NIEHS NIH HHS
Chemical
Reg. No./Substance:
3KX376GY7L/Glutamic Acid; EC 1.15.1.1/Superoxide Dismutase; EC 1.15.1.1/superoxide dismutase 2
Comments/Corrections

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