Please use this identifier to cite or link to this item:
Type: Artigo de periódico
Title: Oxidative Damage Of Mitochondria Induced By 5-aminolevulinic Acid: Role Of Ca2+ And Membrane Protein Thiols.
Author: Vercesi, A E
Castilho, R F
Meinicke, A R
Valle, V G
Hermes-Lima, M
Bechara, E J
Abstract: Reactive oxygen species (ROS) generated by metal-catalyzed 5-aminolevulinic acid (ALA) aerobic oxidation have been shown to damage the inner membrane of isolated rat liver mitochondria by a Ca(2+)-dependent mechanism. The present work describes experiments indicating that this damage can be prevented, but not completely reversed by the additions of catalase, ADP, cyclosporin A and dithiothreitol, as judged by the extent of delta psi regeneration by the injured mitochondria. In contrast, the addition of EGTA, which removes free Ca2+ and, possibly, Fe2+ present both in the intra- and extramitochondrial compartments, causes a prompt and complete regeneration of delta psi, even after long periods of mitochondrial incubations in the presence of ALA. This reversibility suggests that protein alterations such as protein thiol cross-linkings, evidenced by SDS-polyacrylamide gel electrophoresis, are the main cause of increased membrane permeability promoted by ALA oxidation. The inhibition of protein aggregation and fast regeneration of delta psi promoted by EGTA suggest that the binding of Ca2+ to some membrane proteins plays a crucial role in the mechanism of both protein polymerization (pore assembly) and pore opening. The implication of these results with the molecular pathology of acute intermittent porphyria is also discussed.
Subject: Aminolevulinic Acid
Intracellular Membranes
Membrane Potentials
Membrane Proteins
Mitochondria, Liver
Rats, Wistar
Reactive Oxygen Species
Sulfhydryl Compounds
Citation: Biochimica Et Biophysica Acta. v. 1188, n. 1-2, p. 86-92, 1994-Nov.
Rights: fechado
Date Issue: 1994
Appears in Collections:Unicamp - Artigos e Outros Documentos

Files in This Item:
File SizeFormat 
pmed_7947907.pdf661.78 kBAdobe PDFView/Open

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.