Document Detail


Lead inhibits in vitro creatine kinase and pyruvate kinase activity in brain cortex of rats.
MedLine Citation:
PMID:  19925858     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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:
Tatiana Wannmacher Lepper; Evandro Oliveira; Gustavo Duarte Waltereith Koch; Daiane Bolzan Berlese; Luciane Rosa Feksa
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2009-11-16
Journal Detail:
Title:  Toxicology in vitro : an international journal published in association with BIBRA     Volume:  24     ISSN:  1879-3177     ISO Abbreviation:  Toxicol In Vitro     Publication Date:  2010 Apr 
Date Detail:
Created Date:  2010-03-09     Completed Date:  2010-06-22     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8712158     Medline TA:  Toxicol In Vitro     Country:  England    
Other Details:
Languages:  eng     Pagination:  1045-51     Citation Subset:  IM    
Copyright Information:
Copyright (c) 2009 Elsevier Ltd. All rights reserved.
Affiliation:
Departamento de Bioqu?mica, Instituto de Ci?ncias B?sicas da Sa?de, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil.
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MeSH Terms
Descriptor/Qualifier:
Animals
Cerebral Cortex / drug effects,  enzymology*
Creatine Kinase / antagonists & inhibitors*
Cysteamine / pharmacology
Cytosol / drug effects,  enzymology
Dose-Response Relationship, Drug
Enzyme Inhibitors*
Glutathione / pharmacology
Lead / toxicity*
Lead Poisoning, Nervous System / enzymology*
Male
Mitochondria / drug effects,  enzymology
Protective Agents / pharmacology
Pyruvate Kinase / antagonists & inhibitors*
Rats
Rats, Wistar
Subcellular Fractions / drug effects,  enzymology
Sulfhydryl Compounds / metabolism
Chemical
Reg. No./Substance:
0/Enzyme Inhibitors; 0/Protective Agents; 0/Sulfhydryl Compounds; 60-23-1/Cysteamine; 70-18-8/Glutathione; 7439-92-1/Lead; EC 2.7.1.40/Pyruvate Kinase; EC 2.7.3.2/Creatine Kinase

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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