title: Lead inhibits in vitro creatine kinase and pyruvate kinase activity in brain cortex of rats.
abstract: Lead intoxication is a serious occupational disease that constitutes a major public health problem. Lead, a heavy metal, has been used by humans for many technological purposes, which is the main reason for its widespread distribution. The toxic mechanisms of lead on the molecular machinery of living organisms include metal transport, energy metabolism, diverse enzymatic processes, genetic regulation, and membrane ionic channels and signaling molecules. Since lead is able to cross the blood-brain barrier it may cause neurotoxicity. Creatine kinase and pyruvate kinase are two thiol-containing enzymes that exert a key role for cellular energy homeostasis in brain. Our main objective was to investigate the in vitro effect of lead on pyruvate kinase and creatine kinase activities of extracts and subcellular fractions from the brain cortex of rats in the presence or not of thiol-protecting substances such as glutathione and cysteamine. The results showed that lead inhibited the two enzyme activities and the thiol-protecting substances prevented their inhibition. These results suggest that lead inhibits creatine kinase and pyruvate kinase activity by interaction with their thiol groups. Therefore, lead may disrupt energy homeostasis and this effect may contribute to the neurological dysfunction found in lead exposed individuals.
authors.affiliation: Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil.
authors.forename: Tatiana Wannmacher
authors.initials: TW
authors.lastname: Lepper
authors.forename: Evandro
authors.initials: E
authors.lastname: Oliveira
authors.forename: Gustavo Duarte Waltereith
authors.initials: GD
authors.lastname: Koch
authors.forename: Daiane Bolzan
authors.initials: DB
authors.lastname: Berlese
authors.forename: Luciane Rosa
authors.initials: LR
authors.lastname: Feksa
mesh_terms: D000818:Animals; D002540:Cerebral Cortex / Q000187:drug effects / Q000201:enzymology*; D003402:Creatine Kinase / Q000037:antagonists & inhibitors*; D003543:Cysteamine / Q000494:pharmacology; D003600:Cytosol / Q000187:drug effects / Q000201:enzymology; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors; D005978:Glutathione / Q000494:pharmacology; D007854:Lead / Q000633:toxicity*; D020263:Lead Poisoning, Nervous System / Q000201:enzymology*; D008297:Male; D008928:Mitochondria / Q000187:drug effects / Q000201:enzymology; D020011:Protective Agents / Q000494:pharmacology; D011770:Pyruvate Kinase / Q000037:antagonists & inhibitors*; D051381:Rats; D017208:Rats, Wistar; D013347:Subcellular Fractions / Q000187:drug effects / Q000201:enzymology; D013438:Sulfhydryl Compounds / Q000378:metabolism
chemical_list: D004791:Enzyme Inhibitors; D020011:Protective Agents; D013438:Sulfhydryl Compounds; D007854:Lead; D003543:Cysteamine; D011770:Pyruvate Kinase; D003402:Creatine Kinase; D005978:Glutathione