Linked Life Data

18652897

Source:http://linkedlifedata.com/resource/pubmed/id/18652897

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2008-9-16
pubmed:abstractText
Protein interactions of the Amyotrophic Lateral Sclerosis (ALS)-linked copper-zinc superoxide dismutase (hSOD1) G93A mutation were studied using a fluorescence resonance energy transfer (FRET) based screening system. The FRET results confirmed by pull-down immunoprecipitation indicated "gain-of-interaction" of the G93A-hSOD1 mutant with cytosolic malate dehydrogenase (cytMDH)-a key enzyme in the malate-aspartate shuttle which is vital to neurons. Furthermore, cytMDH mRNA expression was upregulated in G93A-hSOD1 expressing cells but endogenous cytMDH enzymatic activity was not enhanced, not even with exogenously added-on enzyme. Consistent with inhibition of the malate-aspartate shuttle, G93A-hSOD1 had lower malate and higher lactate levels compared to non-induced or Wild-Type-hSOD1 expressing cells. Mitochondrial NADH/NAD+ ratio is also elevated. Malate-aspartate shuttle dysfunction may explain the damage to neurons and the vulnerability to impairments of glycolytic pathways in ALS and provide a new target for the development of potential therapies.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
1095-953X
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
32
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
133-41
pubmed:meshHeading
pubmed:year
2008
pubmed:articleTitle
Gain of interaction of ALS-linked G93A superoxide dismutase with cytosolic malate dehydrogenase.
pubmed:affiliation
Department of Neurobiology, Tel Aviv University, Tel Aviv 69978, Israel.
pubmed:publicationType
Journal Article, Comparative Study, Research Support, Non-U.S. Gov't