Inhibition of in vivo leishmanicidal mechanisms by tempol: Nitric oxide down-regulation and oxidant scavenging

Linares, Edlaine; Giorgio, Selma; Augusto, Ohára

doi:10.1016/j.freeradbiomed.2008.01.027

Cited by 33 publications

(37 citation statements)

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“…Under these conditions, all nitric oxide-derived products (nitrate, nitrite, nitrosothiol, nitrosamines, and iron-nitrosyl complexes) are reduced to nitric oxide, which is released into the gas phase and subsequently determined by its chemiluminescence reaction with ozone. The peak areas of the samples were calculated with the instrument software and compared with those of standard solutions of nitrate analyzed under the same experimental conditions (Linares et al, 2008) The levels of nitric oxide-derived products shown correspond to the levels measured in cell homogenates minus the level measured in the buffer, and are expressed as nmol/mg of protein. Total protein in the samples was determined by BCA method (Morton and Evans, 1992).…”

Section: Chemiluminescence Assay Of Nitric Oxide-derived Productsmentioning

confidence: 99%

Evidence of a Ca2+- NO-cGMP signaling pathway controlling zoospore biogenesis in the aquatic fungus Blastocladiella emersonii

Vieira

Linares

Augusto

et al. 2009

Fungal Genetics and Biology

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The sporulation stage of the aquatic fungus Blastocladiella emersonii culminates with the formation and release to the medium of a number of zoospores, which are motile cells responsible for the dispersal of the fungus. The presence in the sporulation solution of 1H-[1,2,4]Oxadiazolo[4,3-a]quinoxalin-1-one (ODQ), a potent and selective inhibitor of nitric oxide-sensitive guanylyl cyclases, completely prevented biogenesis of the zoospores. In addition, this compound was able to significantly reduce cGMP levels, which increase drastically during late sporulation, suggesting the existence of a nitric oxide-dependent mechanism for cGMP synthesis. Furthermore, increased levels of nitric oxide-derived products were detected during sporulation by fluorescence assays using DAF-2 DA, whose signal was drastically reduced in the presence of the nitric oxide synthase inhibitor Nomega-Nitro-L-arginine methyl ester (L-NAME). These results were confirmed by quantitative chemiluminescent determination of the intracellular levels of nitric oxide-derived products. A putative nitric oxide synthase (NOS) activity was detected throughout sporulation, and this enzyme activity decreased significantly when L-NAME and 1-[2-(Trifluoromethyl)phenyl]imidazole (TRIM) were added to the assays. NOS assays carried out in the presence of EGTA showed decreased enzyme activity, suggesting the involvement of calcium ions in enzyme activation. Additionally, expressed sequence tags (ESTs) encoding putative guanylyl cyclases and a cGMP-phosphodiesterase were found in B. emersonii EST database (http://blasto.iq.usp.br), and the mRNA levels of the corresponding genes were observed to increase during sporulation. Altogether, data presented here revealed the presence and expression of guanylyl cyclase and cGMP phosphodiesterase genes in B. emersonii and provided evidence of a Ca(2+)-(*)NO-cGMP signaling pathway playing a role in zoospore biogenesis.

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Section: Chemiluminescence Assay Of Nitric Oxide-derived Productsmentioning

confidence: 99%

Evidence of a Ca2+- NO-cGMP signaling pathway controlling zoospore biogenesis in the aquatic fungus Blastocladiella emersonii

Vieira

Linares

Augusto

et al. 2009

Fungal Genetics and Biology

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“…Application of potential prodrugs to cultures of infected mouse macrophages that were deficient in iNOS caused rapid death of the intracellular protozoan parasite Leishmania major with no host cell toxicity [54]. Therefore, some antileishmanial drugs act via NO modulation [55][56][57].…”

Section: Leishmania Spmentioning

confidence: 99%

Involvement of nitric oxide and its up/down stream molecules in the immunity against parasitic infections

Nahrevanian

2009

Braz J Infect Dis

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Nitric oxide (NO) is a potent mediator with diverse roles in regulating cellular functions and signaling pathways. The NO synthase (NOS) enzyme family consists of three major isoforms, which convey variety of messages between cells, including signals for vasorelaxation, neurotransmission and cytotoxicity. This family of enzymes are generally classified as neuronal NOS (nNOS), endothelial NOS (eNOS) and inducible NOS (iNOS). Increased levels of NO are induced from iNOS during infection; while eNOS and nNOS may be produced at the baseline in normal conditions. An association of some key cytokines appears to be essential for NOS gene regulation in the immunity of infections. Accumulating evidence indicates that parasitic diseases are commonly associated with elevated production of NO. NO plays a role in the immunoregulation and it is implicated in the host non-specific defence in a variety of infections. Nevertheless, the functional role of NO and NOS isoforms in the immune responses of host against the majority of parasites is still highly controversial. In the present review, the role of parasitic infections will be discussed in the controversy related to the NO production and iNOS gene expression in different parasites and a variety of experimental models.

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“…Currently, there is no direct evidence that antioxidant treatments decrease NO in nemertean oocytes by either downregulating NOS activity or scavenging NO, as demonstrated for somatic cells (Bergamini et al 2001, Linares et al 2008, Kim et al 2009, Harput et al 2011. Moreover, even if the antioxidants had been shown to reduce intraoocytic NO, such findings would not preclude the possibility that these broadly acting drugs block GVBD via effects on other targets, including ROS (Nakagawa et al 2010).…”

Section: Discussionmentioning

confidence: 99%

“…Since each of the tested antioxidants can lower NO levels in somatic cells (Bergamini et al 2001, Linares et al 2008, Kim et al 2009, Harput et al 2011 Figure 1 (A) Antioxidants (aa, ascorbic acid; BHA, butylated hydroxyanisole; gallo, gallotannin; NAC, N-acetylcysteine; tem, tempol) block seawater (SW)-induced GVBD in a dose-dependent manner. (B and C) Conversely, such blockage is reversed after coadding 5 mM of the cAMP elevator forskolin (fors) to 200 mM aa, 500 mM BHA, 100 mM gallo, 150 mM NAC, or 150 mM tem.…”

Section: Role Of No During Gvbdmentioning

confidence: 99%

Inhibition of germinal vesicle breakdown by antioxidants and the roles of signaling pathways related to nitric oxide and cGMP during meiotic resumption in oocytes of a marine worm

Stricker

2012

Reproduction

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In mammalian oocytes, cAMP elevations prevent the resumption of meiotic maturation and thereby block nuclear disassembly (germinal vesicle breakdown (GVBD)), whereas nitric oxide (NO) and its downstream mediator cGMP can either inhibit or induce GVBD. Alternatively, some invertebrate oocytes use cAMP to stimulate, rather than inhibit, GVBD, and in such cases, the effects of NO/cGMP signaling on GVBD remain unknown. Moreover, potential interactions between NO/cGMP and AMP-activated kinase (AMPK) have not been assessed during GVBD. Thus, this study analyzed intraoocytic signaling pathways related to NO/cGMP in a marine nemertean worm that uses cAMP to induce GVBD. For such tests, follicle-free nemertean oocytes were stimulated to mature by seawater (SW) and cAMP elevators. Based on immunoblots and NO assays of maturing oocytes, SW triggered AMPK deactivation, NO synthase (NOS) phosphorylation, and an NO elevation. Accordingly, SW-induced GVBD was blocked by treatments involving the AMPK agonist AICAR, antioxidants, the NO scavenger carboxy-PTIO, NOS inhibitors, and cGMP antagonists that target the NO-stimulated enzyme, soluble guanylate cyclase (sGC). Conversely, SW solutions combining NO/cGMP antagonists with a cAMP elevator restored GVBD. Similarly, AICAR plus a cAMP-elevating drug reestablished GVBD while deactivating AMPK and phosphorylating NOS. Furthermore, sGC stimulators and 8-Br-cGMP triggered GVBD. Such novel results indicate that NO/cGMP signaling can upregulate SW-induced GVBD and that cAMP-elevating drugs restore GVBD by overriding the inhibition of various NO/cGMP downregulators, including AMPK. Moreover, considering the opposite effects of intraoocytic cAMP in nemerteans vs mammals, these data coincide with previous reports that NO/cGMP signaling blocks GVBD in rats.

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Inhibition of in vivo leishmanicidal mechanisms by tempol: Nitric oxide down-regulation and oxidant scavenging

Cited by 33 publications

References 50 publications

Evidence of a Ca2+- NO-cGMP signaling pathway controlling zoospore biogenesis in the aquatic fungus Blastocladiella emersonii

Evidence of a Ca2+- NO-cGMP signaling pathway controlling zoospore biogenesis in the aquatic fungus Blastocladiella emersonii

Involvement of nitric oxide and its up/down stream molecules in the immunity against parasitic infections

Inhibition of germinal vesicle breakdown by antioxidants and the roles of signaling pathways related to nitric oxide and cGMP during meiotic resumption in oocytes of a marine worm

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