RGD Reference Report - Cytochrome c oxidase isoform IV-2 is involved in 3-nitropropionic acid-induced toxicity in striatal astrocytes. - Rat Genome Database

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Cytochrome c oxidase isoform IV-2 is involved in 3-nitropropionic acid-induced toxicity in striatal astrocytes.

Authors: Singh, Shilpee  Misiak, Magdalena  Beyer, Cordian  Arnold, Susanne 
Citation: Singh S, etal., Glia. 2009 Nov 1;57(14):1480-91. doi: 10.1002/glia.20864.
RGD ID: 13506652
Pubmed: PMID:19306371   (View Abstract at PubMed)
DOI: DOI:10.1002/glia.20864   (Journal Full-text)

Astrocyte mitochondria play an important role for energy supply and neuronal survival in the brain. Toxic and degenerative processes are largely associated with mitochondrial dysfunction. We, therefore, investigated the effect of 3-nitropropionic acid (NPA), a mitochondrial toxin and in vitro model of Huntington's disease (HD), on mitochondrial function and viability of primary striatal astrocytes. Although NPA is known as an irreversible inhibitor of succinate dehydrogenase, we observed an increase of astrocyte ATP levels after NPA treatment. This effect could be explained by NPA-mediated alterations of cytochrome c oxidase subunit IV isoform (COX IV) expression. The up-regulation of COX isoform IV-2 caused an increased enzyme activity at the expense of elevated mitochondrial peroxide production causing increased cell death. The application of a small interfering RNA against COX IV-2 revealed the causal implication of COX isoform IV-2 in NPA-mediated elevation of oxidative stress and necrotic cell death. Thus, we propose a novel, additional mechanism of NPA-induced cell stress and death which is based on structural and functional changes of astrocyte COX and which could indirectly impair neuronal survival.



Gene-Chemical Interaction Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
COX4I2Human3-nitropropanoic acid increases expression ISOCox4i2 (Mus musculus)3-nitropropionic acid increases expression of Cox4i2 mRNA in primary astrocytesRGD 
Cox4i2Rat3-nitropropanoic acid increases expression ISOCox4i2 (Mus musculus)3-nitropropionic acid increases expression of Cox4i2 mRNA in primary astrocytesRGD 
Cox4i2Mouse3-nitropropanoic acid increases expression EXP 3-nitropropionic acid increases expression of Cox4i2 mRNA in primary astrocytesRGD 

Objects Annotated

Genes (Rattus norvegicus)
Cox4i2  (cytochrome c oxidase subunit 4i2)

Genes (Mus musculus)
Cox4i2  (cytochrome c oxidase subunit 4I2)

Genes (Homo sapiens)
COX4I2  (cytochrome c oxidase subunit 4I2)

Objects referenced in this article
Gene Mt-co2 mitochondrially encoded cytochrome c oxidase II Rattus norvegicus

Additional Information