Linked Life Data

3773883

Source:http://linkedlifedata.com/resource/pubmed/id/3773883

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
1986-12-10
pubmed:abstractText
The neurotoxic gamma-diketone, 2,5-hexanedione, reacts with axonal protein amine residues to form 2,5-dimethylpyrrole adducts. Current evidence implicates this reaction as the potentially critical step in gamma-diketone neurotoxicity, although it is unclear whether pyrrole formation per se is sufficient to induce neuropathy or whether secondary autoxidative reactions are also required. The present in vitro study examines aspects of pyrrole formation and the secondary phenomena of chromophore development and covalent protein crosslinking in 2,5-hexanedione-treated protein. p-Dimethylaminobenzaldehyde (DMAB)-detectable pyrrole concentrations decreased linearly with time when pyrrolylated bovine serum albumin (pyrrole-BSA) was incubated under air, but remained unchanged following N2 incubation. The air-induced decrease was accompanied by the appearance of chromophores and crosslinked protein. Covalent crosslinking of pyrrole-BSA was pH-dependent, with relatively increased intermolecular bridging at pH 7.4 as compared to pH 9.5. Chromophore formation and the loss in DMAB-detectable pyrrole were also accelerated at the lower pH. Autoxidative parameters were inhibited in the presence of a free radical scavenger (ascorbic acid) but induced by free radical initiators (potassium persulfate and 2,2'-azobis[2-amidinopropane hydrochloride]). In vitro incubation followed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis of combinations of bovine serum albumin, ribonuclease, pyrrole-BSA, and pyrrolylated ribonuclease revealed that the intermolecular crosslinking pathway was mediated by pyrrole-pyrrole bridging. These findings demonstrate that the secondary autoxidative phenomena following pyrrole adduct formation in gamma-diketone-treated protein proceed via pH-dependent, free radical-mediated mechanisms. If similar mechanisms are present in vivo, the results also suggest that intermolecular covalent crosslinking of pyrrolylated axonal protein may be less widespread and more specific than previously thought.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
0026-895X
pubmed:author
pubmed:issnType
Print
pubmed:volume
30
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
452-8
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
1986
pubmed:articleTitle
Mechanisms of in vitro pyrrole adduct autoxidation in 2,5-hexanedione-treated protein.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.