Data/hora: 05/06/2024 03:39:02

Provedor de dados: | 56
País: | Brazil
Título: | Glutathione and the redox control system trypanothione/trypanothione reductase are involved in the protection of Leishmania spp. against nitrosothiol-induced cytotoxicity
Autores: | Romão,P.R.T.; Tovar,J.; Fonseca,S.G.; Moraes,R.H.; Cruz,A.K.; Hothersall,J.S.; Noronha-Dutra,A.A.; Ferreira,S.H.; Cunha,F.Q.
Data: | 2006-03-01
Ano: | 2006
Palavras-chave: | Leishmania; Glutathione; Trypanothione; Trypanothione reductase; Nitric oxide; Free radicals.
Resumo: | Glutathione is the major intracellular antioxidant thiol protecting mammalian cells against oxidative stress induced by oxygen- and nitrogen-derived reactive species. In trypanosomes and leishmanias, trypanothione plays a central role in parasite protection against mammalian host defence systems by recycling trypanothione disulphide by the enzyme trypanothione reductase. Although Kinetoplastida parasites lack glutathione reductase, they maintain significant levels of glutathione. The aim of this study was to use Leishmania donovani trypanothione reductase gene mutant clones and different Leishmania species to examine the role of these two individual thiol systems in the protection mechanism against S-nitroso-N-acetyl-D,L-penicillamine (SNAP), a nitrogen-derived reactive species donor. We found that the resistance to SNAP of different species of Leishmania was inversely correlated with their glutathione concentration but not with their total low-molecular weight thiol content (about 0.18 nmol/10(7) parasites, regardless Leishmania species). The glutathione concentration in L. amazonensis, L. donovani, L. major, and L. braziliensis were 0.12, 0.10, 0.08, and 0.04 nmol/10(7) parasites, respectively. L. amazonensis, that have a higher level of glutathione, were less susceptible to SNAP (30 and 100 µM). The IC50 values of SNAP determined to L. amazonensis, L. donovani, L. major, and L. braziliensis were 207.8, 188.5, 160.9, and 83 µM, respectively. We also observed that L. donovani mutants carrying only one trypanothione reductase allele had a decreased capacity to survive (~40%) in the presence of SNAP (30-150 µM). In conclusion, the present data suggest that both antioxidant systems, glutathione and trypanothione/trypanothione reductase, participate in protection of Leishmania against the toxic effect of nitrogen-derived reactive species.
Tipo: | Info:eu-repo/semantics/article
Idioma: | Inglês
Identificador: | http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0100-879X2006000300006
Editor: | Associação Brasileira de Divulgação Científica
Relação: | 10.1590/S0100-879X2006000300006
Formato: | text/html
Fonte: | Brazilian Journal of Medical and Biological Research  v.39 n.3 2006
Fonte: | info:eu-repo/semantics/openAccess