Linked Life Data

15075342

Source:http://linkedlifedata.com/resource/pubmed/id/15075342

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
26
pubmed:dateCreated
2004-6-21
pubmed:abstractText
Coenzyme Q(0) (Q(0)), a strong electrophile, is toxic to insulin-producing cells. Q(0) was incubated with rat and human pancreatic islets and INS-1 insulinoma cells, and its attachment to cellular proteins was studied with Western analysis using antiserum raised against the benzoquinone ring structure of ubiquinone (anti-Q). Q(0) covalently bonded to two proteins, one of 50 kDa and another of 70 kDa. Both proteins were found to be mitochondrial in human and rat islet cells and in many rat organs. Mitochondria were incubated with Q(0), and affinity-purified anti-Q was used to immunoprecipitate the 50-kDa protein. Amino acid sequencing identified it as dihydrolipoamide succinyltransferase, the E2 component of the alpha-ketoglutarate dehydrogenase complex (KDC). Western analysis also showed that Q bonds to the E2 components of the purified KDC and (0)the pyruvate dehydrogenase complex (PDC). Dihydrolipoamide acetyltransferase, the E2 of the PDC, has a molecular mass of 70 kDa, and the 70-kDa protein was inferred to be this enzyme. Q(0) was found to bond only to proteins containing dihydrolipoate, and in preparations of mitochondria, thiol reducing agents facilitated the attachment of Q(0), but oxidizing agents prevented it, suggesting that Q(0) bonds to thiols of dihydrolipoamide. Incubation of human or pig PDC with Q(0) followed by matrix-assisted laser desorption ionization time-of-flight and liquid chromatography/electrospray ionization mass spectrometry analyses of chymotrypsin-digested peptides of PDC E2 confirmed that Q(0) bonds to the dihydrolipoamide in these proteins. In mitochondria, coenzymes Q(1) and Q(2) did not bond to the 50-kDa protein but competed with the bonding of Q(0) to this protein. The prevention by Q(1) of characteristics the bonding of Q(0) to KDC E2, as well as other of the Q(0) effect, are reminiscent of the action of Q(0) on the mitochondrial permeability transition pore described previously (Fontaine, E., Ichas, F., and Bernardi, P. (1998) J. Biol. Chem. 273, 25734-25740).
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
25
pubmed:volume
279
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
27278-85
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed-meshheading:15075342-Acetyltransferases, pubmed-meshheading:15075342-Animals, pubmed-meshheading:15075342-Benzoquinones, pubmed-meshheading:15075342-Binding, Competitive, pubmed-meshheading:15075342-Cattle, pubmed-meshheading:15075342-Cells, Cultured, pubmed-meshheading:15075342-Dihydrolipoyllysine-Residue Acetyltransferase, pubmed-meshheading:15075342-Humans, pubmed-meshheading:15075342-Immunoblotting, pubmed-meshheading:15075342-Islets of Langerhans, pubmed-meshheading:15075342-Ketoglutarate Dehydrogenase Complex, pubmed-meshheading:15075342-Mitochondria, pubmed-meshheading:15075342-Precipitin Tests, pubmed-meshheading:15075342-Pyruvate Dehydrogenase Complex, pubmed-meshheading:15075342-Rats, pubmed-meshheading:15075342-Rats, Sprague-Dawley, pubmed-meshheading:15075342-Spectrometry, Mass, Matrix-Assisted Laser..., pubmed-meshheading:15075342-Subcellular Fractions, pubmed-meshheading:15075342-Sulfhydryl Compounds, pubmed-meshheading:15075342-Swine, pubmed-meshheading:15075342-Thioctic Acid, pubmed-meshheading:15075342-Ubiquinone
pubmed:year
2004
pubmed:articleTitle
Immunochemical identification of coenzyme Q0-dihydrolipoamide adducts in the E2 components of the alpha-ketoglutarate and pyruvate dehydrogenase complexes partially explains the cellular toxicity of coenzyme Q0.
pubmed:affiliation
Childrens Diabetes Center, University of Wisconsin Medical School, Madison, Wisconsin 53706, USA. mjmacdon@wisc.edu
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't