Mechanisms of in vitro pyrrole adduct autoxidation in 2,5- hexanedione-treated protein.
Mol Pharmacol 1986 Nov; 30(5):452-458
In-vitro studies were conducted to investigate pyrrole formation, chromophore development and covalent protein crosslinking in bovine protein treated with 2,5-hexanedione (2935446) (HD), a known neurotoxic diketone. Pyrrole concentration detectable by p- dimethylaminobenzaldehyde (DMAB) decreased linearly as a function of time in aerobically incubated, pyrrole treated serum albumin accompanied by the formation of chromophores and crosslinked protein; incubation under nitrogen did not significantly affect the concentration of pyrrole, regardless of pH. Intermolecular covalent crosslinking of pyrrole and serum bovine albumin was dependent on the incubation pH, bridging being higher at pH 7.4 than at pH 9.5; the same pattern prevailed for chromosome formation and the loss of DMAB detectable pyrrole. Ascorbic-acid and free radical initiators such as potassium-persulfate and 2,2'-azobis(2-amidinopropane- hydrochloride), inhibited and induced covalent crosslinking of pyrrolated bovine serum albumin, respectively. Identification of amino acid moieties participating in the crosslinking process, using polyacrylamide gel electrophoretic analysis of a variety of incubation mixtures of bovine serum albumin, pyrrolated bovine serum albumin, ribonuclease, and pyrrolated ribonuclease, indicated that intermolecular crosslinking in pyrrolated protein was mediated by bridging of pyrrole to pyrrole. The authors conclude that additional research is required to extend the findings of the present study, in-vitro, to in-vivo systems exposed to diketones.
NIOSH-Publication; NIOSH-Grant; Neurotoxic-effects; Biochemical-analysis; Biochemical-tests; Biochemical-indicators; Toxicology; Ketones; Neurotoxicity; Neurotoxins; Oxidation;
Biochem and Genetic Toxicology New York State Dept of Health Empire State Plaza Albany, N Y 12201
Neurotoxic Disorders; Neurotoxic-effects;
New York State Dept of Health, New York, New York