Cysteine protease as a target for nitric oxide in parasitic organisms

Colasanti, Marco; Salvati, Luca; Venturini, Giorgio; Ascenzi, Paolo; Gradoni, Luigi

doi:10.1016/s1471-4922(01)02191-2

Cited by 28 publications

(12 citation statements)

References 10 publications

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“…To do this we assessed how metrics of parasite fitness and one aspect of midgut-mediated immunity, the production of nitric oxide (NO) by the enzyme nitric oxide synthase (NOS), were affected by varying mean ambient temperature and providing a subset of mosquitoes with access to an essential amino acid, L-Arginine (L-Arg). NO is a free radical gas that can react with a variety of oxidants to generate cytotoxic reactive nitrogen species [RNS, 17, 18]. RNS are toxic to a wide diversity of pathogens [19] and are key to the mosquito midgut immune response toward Plasmodium parasites [2–4, 20].…”

Section: Introductionmentioning

confidence: 99%

Ambient temperature and dietary supplementation interact to shape mosquito vector competence for malaria

Murdock

Blanford

Luckhart

et al. 2014

Journal of Insect Physiology

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The extent to which environmental factors influence the ability of Anopheles mosquitoes to transmit malaria parasites remains poorly explored. Environmental variation, such as change in ambient temperature, will not necessarily influence the rates of host and parasite processes equivalently, potentially resulting in complex effects on infection outcomes. As proof of principle, we used Anopheles stephensi and the rodent malaria parasite, Plasmodium yoelii, to examine the effects of a range of constant temperatures on one aspect of host defense (detected as alterations in expression of nitric oxide synthase gene – NOS) to parasite infection. We experimentally boosted mosquito midgut immunity to infection through dietary supplementation with the essential amino acid L-Arginine (L-Arg), which increases midgut NO levels by infection-induced NOS catalysis in A. stephensi. At intermediate temperatures, supplementation reduced oocyst prevalence, oocyst intensity, and sporozoite prevalence suggesting that the outcome of parasite infection was potentially dependent upon the rate of NOS-mediated midgut immunity. At low and high temperature extremes, however, infection was severely constrained irrespective of supplementation. The effects of L-Arg appeared to be mediated by NO-dependent negative feedback on NOS expression, as evidenced by depressed NOS expression in L-Arg treated groups at temperatures where supplementation decreased parasite infection. These results suggest the need to consider the direct (e.g. effects of mosquito body temperature on parasite physiology) and indirect effects (e.g. mediated through changes in mosquito physiology / immunity) of environmental factors on mosquito-malaria interactions in order to understand natural variation in vector competence.

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Section: Introductionmentioning

confidence: 99%

Ambient temperature and dietary supplementation interact to shape mosquito vector competence for malaria

Murdock

Blanford

Luckhart

et al. 2014

Journal of Insect Physiology

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show abstract

“…Thus, NO-donors inhibit the activity of falcipain, the papain-like cysteine protease involved in hemoglobin degradation by P. falciparum trophozoites. Falcipain inactivation blocks development of P. falciparum, and inhibition of Plasmodium vinckei falcipainhomologous cysteine protease cures murine infection (14). Besides the NO-mediated chemical modification of host cysteine-containing proteins could also influence parasite survival (5).…”

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confidence: 99%

Is There an Answer? ‐ Coordinated by Frank Vella

Ascenzi

Gradoni²,

Visca³

2004

IUBMB Life

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“…Evidências têm sugerido que cisteíno proteases dos parasitas seriam inibidas pelo NO, e deste modo o efeito parasiticida desse radical poderia ser explicado. Especificamente, doadores de NO podem inibir a atividade da cruzipaina (Catepsina L-like de T.cruzi), da falcipaina (Catepsina L-like de P.falciparum) e de cisteíno proteases de Leishmania infantum, influenciando negativamente na sobrevivência do parasita (COLASANTI, et al, 2001). …”

Section: Rhodniusunclassified

Genes de cisteíno proteases (Catepsina L-like) de Trypanosoma rangeli: polimorfismo, relações filogenéticas e alvos para diagnóstico e genotipagem.

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Cysteine protease as a target for nitric oxide in parasitic organisms

Cited by 28 publications

References 10 publications

Ambient temperature and dietary supplementation interact to shape mosquito vector competence for malaria

Ambient temperature and dietary supplementation interact to shape mosquito vector competence for malaria

Is There an Answer? ‐ Coordinated by Frank Vella

Genes de cisteíno proteases (Catepsina L-like) de Trypanosoma rangeli: polimorfismo, relações filogenéticas e alvos para diagnóstico e genotipagem.

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