Leishmania amazonensis: early proteinase activities during promastigote–amastigote differentiation in vitro

Alves, Carlos Roberto; Cortê-Real, Suzana; Bourguignon, Saulo Cabral; Chaves, C.S.; Saraiva, Elvira M.

doi:10.1016/j.exppara.2004.10.005

Cited by 62 publications

(54 citation statements)

References 49 publications

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“…Axenic amastigotes were obtained as described previously (20)(21)(22). Briefly, promastigotes of both parasite species, in the logarithmic growth phase (5 ϫ 10 5 cells/ml), were seeded in axenic medium (Schneider's medium [pH 7.2] containing 10 mM HEPES buffer, 1 mM L-glutamine, 60 IU/ml penicillin, and 60 g/ml streptomycin) and incubated for 24 h at 26°C.…”

Section: Methodsmentioning

confidence: 99%

Epoxy-α-Lapachone Has In Vitro and In Vivo Anti-Leishmania (Leishmania) amazonensis Effects and Inhibits Serine Proteinase Activity in This Parasite

Souza-Silva

Bourguignon

Pereira

et al. 2015

Antimicrob Agents Chemother

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Leishmania (Leishmania) amazonensis is a protozoan that causes infections with a broad spectrum of clinical manifestations. The currently available chemotherapeutic treatments present many problems, such as several adverse side effects and the development of resistant strains. Natural compounds have been investigated as potential antileishmanial agents, and the effects of epoxy-␣-lapachone on L. (L.) amazonensis were analyzed in the present study. This compound was able to cause measurable effects on promastigote and amastigote forms of the parasite, affecting plasma membrane organization and leading to death after 3 h of exposure. This compound also had an effect in experimentally infected BALB/c mice, causing reductions in paw lesions 6 weeks after treatment with 0.44 mM epoxy-␣-lapachone (mean lesion area, 24.9 ؎ 2.0 mm 2 ), compared to untreated animals (mean lesion area, 30.8 ؎ 2.6 mm 2 ) or animals treated with Glucantime (mean lesion area, 28.3 ؎ 1.5 mm 2 ). In addition, the effects of this compound on the serine proteinase activities of the parasite were evaluated. Serine proteinase-enriched fractions were extracted from both promastigotes and amastigotes and were shown to act on specific serine proteinase substrates and to be sensitive to classic serine proteinase inhibitors (phenylmethylsulfonyl fluoride, aprotinin, and antipain). These fractions were also affected by epoxy-␣-lapachone. Furthermore, in silico simulations indicated that epoxy-␣-lapachone can bind to oligopeptidase B (OPB) of L. (L.) amazonensis, a serine proteinase, in a manner similar to that of antipain, interacting with an S1 binding site. This evidence suggests that OPB may be a potential target for epoxy-␣-lapachone and, as such, may be related to the compound's effects on the parasite.

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Section: Methodsmentioning

confidence: 99%

Epoxy-α-Lapachone Has In Vitro and In Vivo Anti-Leishmania (Leishmania) amazonensis Effects and Inhibits Serine Proteinase Activity in This Parasite

Souza-Silva

Bourguignon

Pereira

et al. 2015

Antimicrob Agents Chemother

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“…The activity of aspartic peptidases was first demonstrated in 2005 [191]. Alves and co-workers showed that metallo, serine and aspartic peptidase activities are down-regulated during the shock-induced transformation of promastigotes into amastigotes, by the hydrolysis of specific chromogenic substrates.…”

Section: Aspartic Peptidasesmentioning

confidence: 99%

Biological Roles of Peptidases in Trypanosomatids~!2009-11-26~!2010-02-15~!2010-03-18~!

Vermelho

Branquinha²,

d’Avila-Levy³

et al. 2010

TOPARAJ

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Abstract:In this review, we report the recent developments in the characterization of peptidases and their possible biological functions in the Trypanosomatidae family. The focus will be on peptidases from Trypanosoma cruzi, Leishmania spp., African trypanosomes and plant and insect trypanosomatids. There are numerous events in parasite development where the involvement of peptidases has been established, and they will be approached in the present review. Also in this review we will discuss the central roles have been proposed for peptidases in diverse processes such as virulence, host cell interaction and invasion, catabolism of host proteins, differentiation, cell cycle progression and both stimulation and evasion of host immune responses.

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“…However, the incidence of HIV-Leishmania co-infections has been decreasing since the introduction of HAART, in which aspartic-type protease inhibitors were included [94,95] . These findings instigated the research to confirm the possible connection between aspartic protease expression and basic molecular processes in Leishmania [96][97][98][99][100][101][102][103] . Our group showed that HIV protease inhibitors were able to impair in vitro proliferation of L. amazonensis promastigotes in a dose-dependent manner and in different extensions, in which nelfinavir (IC50 = 15.1 ± 1.1 μmol/L), lopinavir (IC50 = 16.5 ± 0.8 μmol/L) and amprenavir (IC50 = 62.0 ± 2.1 μmol/L) were the most potent compounds [103] .…”

Section: F Pedrosoimentioning

confidence: 99%

Protease expression by microorganisms and its relevance to crucial physiological/pathological events

Santos¹

2011

WJBC

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The treatment of infections caused by fungi and trypanosomatids is difficult due to the eukaryotic nature of these microbial cells, which are similar in several biochemical and genetic aspects to host cells. Aggravating this scenario, very few antifungal and anti-trypanosomatidal agents are in clinical use and, therefore, therapy is limited by drug safety considerations and their narrow spectrum of activity, efficacy and resistance. The search for new bioactive agents against fungi and trypanosomatids has been expanded because progress in biochemistry and molecular biology has led to a better understanding of important and essential pathways in these microorganisms including nutrition, growth, proliferation, signaling, differentiation and death. In this context, proteolytic enzymes produced by these eukaryotic microorganisms are appointed and, in some cases, proven to be excellent targets for searching novel natural and/or synthetic pharmacological compounds, in order to cure or prevent invasive fungal/trypanosomatid diseases. With this task in mind, our research group and others have focused on aspartic-type proteases, since the activity of this class of hydrolytic enzymes is directly implicated in several facets of basic biological processes of both fungal and trypanosomatid cells as well as due to the participation in numerous events of interaction between these microorganisms and host structures. In the present paper, a concise revision of the beneficial effects of aspartic protease inhibitors, with emphasis on the aspartic protease inhibitors used in the anti-human immunodeficiency virus therapy, will be presented and discussed using our experience with the following microbial models: the yeast Candida albicans , the filamentous fungus Fonsecaea pedrosoi and the protozoan trypanosomatid Leishmania amazonensis .

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Leishmania amazonensis: early proteinase activities during promastigote–amastigote differentiation in vitro

Cited by 62 publications

References 49 publications

Epoxy-α-Lapachone Has In Vitro and In Vivo Anti-Leishmania (Leishmania) amazonensis Effects and Inhibits Serine Proteinase Activity in This Parasite

Epoxy-α-Lapachone Has In Vitro and In Vivo Anti-Leishmania (Leishmania) amazonensis Effects and Inhibits Serine Proteinase Activity in This Parasite

Biological Roles of Peptidases in Trypanosomatids~!2009-11-26~!2010-02-15~!2010-03-18~!

Protease expression by microorganisms and its relevance to crucial physiological/pathological events

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