Heme-Induced ROS in Trypanosoma Cruzi Activates CaMKII-Like That Triggers Epimastigote Proliferation. One Helpful Effect of ROS
| Autor: | Marcia Cristina Paes, Natália Pereira de Almeida Nogueira, Sergio Ranto Dalmau, Cintia Fernandes de Souza, Pedro Elias Sultano, G.A.T. Laranja, Roberta Eitler Bruno, Claudio A. Masuda, Luís Henrique Monteiro Leal, Marcus F. Oliveira, Renata L.S. Goncalves, Francis M. S. Saraiva, Marsen Garcia Pinto Coelho |
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| Jazyk: | angličtina |
| Rok vydání: | 2011 |
| Předmět: |
Science
Trypanosoma cruzi Heme Protozoology Biochemistry Microbiology Antioxidants Lipid peroxidation Redox Signaling chemistry.chemical_compound Enzyme activator Ca2+/calmodulin-dependent protein kinase parasitic diseases Chemical Biology Molecular Cell Biology Signaling in Cellular Processes Animals Protein kinase A Biology Protein Kinase Inhibitors chemistry.chemical_classification Reactive oxygen species Life Cycle Stages Multidisciplinary biology biology.organism_classification Cell biology Host-Pathogen Interaction Enzyme Activation Kinetics chemistry Medicine Parastic Protozoans Lipid Peroxidation Signal transduction Calcium-Calmodulin-Dependent Protein Kinase Type 2 Reactive Oxygen Species Oxidation-Reduction Research Article Signal Transduction |
| Zdroj: | PLoS ONE PLoS ONE, Vol 6, Iss 10, p e25935 (2011) |
| ISSN: | 1932-6203 |
| Popis: | Heme is a ubiquitous molecule that has a number of physiological roles. The toxic effects of this molecule have been demonstrated in various models, based on both its pro-oxidant nature and through a detergent mechanism. It is estimated that about 10 mM of heme is released during blood digestion in the blood-sucking bug's midgut. The parasite Trypanosoma cruzi, the agent of Chagas' disease, proliferates in the midgut of the insect vector; however, heme metabolism in trypanosomatids remains to be elucidated. Here we provide a mechanistic explanation for the proliferative effects of heme on trypanosomatids. Heme, but not other porphyrins, induced T. cruzi proliferation, and this phenomenon was accompanied by a marked increase in reactive oxygen species (ROS) formation in epimastigotes when monitored by ROS-sensitive fluorescent probes. Heme-induced ROS production was time- and concentration-dependent. In addition, lipid peroxidation and the formation of 4-hydroxy-2-nonenal (4-HNE) adducts with parasite proteins were increased in epimastigotes in the presence of heme. Conversely, the antioxidants urate and GSH reversed the heme-induced ROS. Urate also decreased parasite proliferation. Among several protein kinase inhibitors tested only specific inhibitors of CaMKII, KN93 and Myr-AIP, were able to abolish heme-induced ROS formation in epimastigotes leading to parasite growth impairment. Taken together, these data provide new insight into T. cruzi- insect vector interactions: heme, a molecule from the blood digestion, triggers epimastigote proliferation through a redox-sensitive signalling mechanism. |
| Databáze: | OpenAIRE |
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