Inactivation of Trypanosoma cruzi dihydrolipoamide dehydrogenase by leukocyte myeloperoxidase systems: role of hypochloride and nitrite related radicals.
Dihydrolipoamide dehydrogenase (LADH) from Trypanosoma cruzi, the causative agent of Chagas' disease, was inactivated by treatment with myeloperoxidase (MPO)-dependent systems. LADH lipoamide reductase and diaphorase activities decreased as a function of incubation time and composition of the MPO/H2O2/halide system, a transient increase preceding the loss of diaphorase activity. Iodide, bromide, thiocyanide and chloride were effective components of MPO/H2O2 or MPO/NADH systems. Catalase prevented LADH inactivation by the MPO/NADH/halide systems in agreement with H2O2 production by NADH-supplemented LADH. Thiol compounds (L-cysteine, N-acetylcysteine, penicillamine, N-(2-mercaptopropionylglycine) and Captopril prevented LADH inactivation by the MPO/H2O2/NaCl system and by NaOCl, thus supporting HOCl as agent of the MPO/H2O2/NaCl system. MPO/H2O2/NaNO2 and MPO/NADH/NaNO2 inactivated LADH, the reaction being prevented by MPO inhibitors and thiol compounds. T. cruzi LADH was affected by MPO-dependent systems like myocardial LADH, allowance being made for the variation of the diaphorase activity and the greater sensitivity of the T. cruzi enzyme to MPO/H2O2/halide systems.
Gutiérrez-Correa
J
J
Bioenergetics Research Centre, School of Medicine, University of Buenos Aires, Paraguay, Argentina.
Krauth-Siegel
R L
RL
Stoppani
A O
AO
D000111:Acetylcysteine / Q000494:pharmacology; D000818:Animals; D001965:Bromides / Q000494:pharmacology; D002216:Captopril / Q000494:pharmacology; D002374:Catalase / Q000494:pharmacology; D003545:Cysteine / Q000494:pharmacology; D003602:Cytotoxicity, Immunologic; D008058:Dihydrolipoamide Dehydrogenase / Q000037:antagonists & inhibitors*; D005978:Glutathione / Q000494:pharmacology; D005998:Glycine / Q000031:analogs & derivatives / Q000494:pharmacology; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D006997:Hypochlorous Acid / Q000494:pharmacology*; D007700:Kinetics; D009206:Myocardium / Q000201:enzymology; D009243:NAD / Q000378:metabolism; D009504:Neutrophils / Q000201:enzymology / Q000502:physiology*; D009573:Nitrites / Q000494:pharmacology*; D010084:Oxidation-Reduction; D010396:Penicillamine / Q000494:pharmacology; D009195:Peroxidase / Q000502:physiology*; D015800:Protozoan Proteins / Q000037:antagonists & inhibitors*; D017382:Reactive Oxygen Species / Q000378:metabolism; D011994:Recombinant Proteins / Q000037:antagonists & inhibitors; D016897:Respiratory Burst; D012965:Sodium Chloride / Q000494:pharmacology; D017670:Sodium Compounds / Q000494:pharmacology; D013438:Sulfhydryl Compounds / Q000494:pharmacology; D008063:Thioctic Acid / Q000031:analogs & derivatives / Q000378:metabolism; D014349:Trypanosoma cruzi / Q000201:enzymology*; D014364:Tryptophan / Q000494:pharmacology; D014443:Tyrosine / Q000494:pharmacology
D001965:Bromides; C110658:N-(2-mercaptoproprionyl)-glycine; D009573:Nitrites; D015800:Protozoan Proteins; D017382:Reactive Oxygen Species; D011994:Recombinant Proteins; D017670:Sodium Compounds; D013438:Sulfhydryl Compounds; D009243:NAD; D014443:Tyrosine; D012965:Sodium Chloride; D006997:Hypochlorous Acid; D008063:Thioctic Acid; D014364:Tryptophan; C013091:lipoamide; D002216:Captopril; D006861:Hydrogen Peroxide; D002374:Catalase; D009195:Peroxidase; D008058:Dihydrolipoamide Dehydrogenase; D005978:Glutathione; D010396:Penicillamine; D003545:Cysteine; C027938:sodium bromide; D005998:Glycine; D000111:Acetylcysteine