Linked Life Data

17189252

Source:http://linkedlifedata.com/resource/pubmed/id/17189252

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
8
pubmed:dateCreated
2007-2-19
pubmed:abstractText
NADH dehydrogenase subunit 2, encoded by the mtDNA, has been associated with resistance to autoimmune type I diabetes (T1D) in a case control study. Recently, we confirmed a role for the mouse ortholog of the protective allele (mt-Nd2(a)) in resistance to T1D using genetic analysis of outcrosses between T1D-resistant ALR and T1D-susceptible NOD mice. We sought to determine the mechanism of disease protection by elucidating whether mt-Nd2(a) affects basal mitochondrial function or mitochondrial function in the presence of oxidative stress. Two lines of reciprocal conplastic mouse strains were generated: one with ALR nuclear DNA and NOD mtDNA (ALR.mt(NOD)) and the reciprocal with NOD nuclear DNA and ALR mtDNA (NOD.mt(ALR)). Basal mitochondrial respiration, transmembrane potential, and electron transport system enzymatic activities showed no difference among the strains. However, ALR.mt(NOD) mitochondria supported by either complex I or complex II substrates produced significantly more reactive oxygen species when compared with both parental strains, NOD.mt(ALR) or C57BL/6 controls. Nitric oxide inhibited respiration to a similar extent for mitochondria from the five strains due to competitive antagonism with molecular oxygen at complex IV. Superoxide and hydrogen peroxide generated by xanthine oxidase did not significantly decrease complex I function. The protein nitrating agents peroxynitrite or nitrogen dioxide radicals significantly decreased complex I function but with no significant difference among the five strains. In summary, mt-Nd2(a) does not confer elevated resistance to oxidative stress; however, it plays a critical role in the control of the mitochondrial reactive oxygen species production.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
23
pubmed:volume
282
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
5171-9
pubmed:dateRevised
2007-11-15
pubmed:meshHeading
pubmed-meshheading:17189252-Alleles, pubmed-meshheading:17189252-Animals, pubmed-meshheading:17189252-Diabetes Mellitus, Type 1, pubmed-meshheading:17189252-Electron Transport, pubmed-meshheading:17189252-Electron Transport Complex I, pubmed-meshheading:17189252-Free Radical Scavengers, pubmed-meshheading:17189252-Inbreeding, pubmed-meshheading:17189252-Membrane Potential, Mitochondrial, pubmed-meshheading:17189252-Mice, pubmed-meshheading:17189252-Mice, Inbred NOD, pubmed-meshheading:17189252-Mitochondria, Liver, pubmed-meshheading:17189252-Mitochondrial Proteins, pubmed-meshheading:17189252-Nitric Oxide, pubmed-meshheading:17189252-Oxidative Stress, pubmed-meshheading:17189252-Oxygen Consumption, pubmed-meshheading:17189252-Protein Subunits, pubmed-meshheading:17189252-Reactive Oxygen Species, pubmed-meshheading:17189252-Species Specificity, pubmed-meshheading:17189252-Xanthine Oxidase
pubmed:year
2007
pubmed:articleTitle
Nuclear and mitochondrial interaction involving mt-Nd2 leads to increased mitochondrial reactive oxygen species production.
pubmed:affiliation
Department of Pediatrics, the University of Pittsburgh School of Medicine and The Children's Hospital of Pittsburgh, Pittsburgh, Pennsylvania 15213, USA.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural