Control of <i>Trypanosoma cruzi</i> Epimastigote Motility through the Nitric Oxide Pathway

Pereira, Claudio A.; Paveto, Cristina; Espinosa, Joaquín M.; Alonso, Guillermo D.; Flawá, Mirtha M.; Torres, Héctor N.

doi:10.1111/j.1550-7408.1997.tb05952.x

Cited by 27 publications

(20 citation statements)

References 15 publications

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“…In addition, the existence of the nitric oxide pathway in T. cruzi was demonstrated recently by this laboratory. This signaling pathway involves a putative L-glutamate/ N-methyl-D-aspartate receptor, a nitric oxide synthase, and a guanylyl cyclase and seems to be a control step in epimastigote flagellar motility (7,8). The existence of a high affinity and very specific L-arginine transporter was also demonstrated in T. cruzi epimastigotes.…”

mentioning

confidence: 94%

Trypanosoma cruzi Arginine Kinase Characterization and Cloning

Pereira

Alonso

Paveto

et al. 2000

Journal of Biological Chemistry

170

129

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N-Phosphorylated guanidino compounds, commonly referred to as phosphagens, play a critical role as an energy reserve because of the high energy phosphate that can be transferred when the renewal of ATP is needed. It has also been proposed that these compounds function in spatial buffering of cellular energy production sites. So, phosphagens act as reserves not only of ATP but also of inorganic phosphate, which is mostly returned to the medium by metabolic consumption of ATP. Phosphoarginine is the main reserve of high energy phosphate compounds in a wide variety of invertebrates. In addition phosphocreatine, phosphoglycocyamine, phosphotaurocyamine, phosphohypotaurocyamine, phosphoopheline, and phospholombricine are also found, whereas in vertebrates the only one present is phosphocreatine (1, 2).Arginine kinase (EC 2.7.3.3) is a member of a conserved family of phosphotransferases which also includes creatine kinase. These enzymes catalyze the reversible transfer of a phosphoryl group from ATP to a guanidino acceptor, which can be either an amino acid (e.g. lombricine or arginine) or a carboxylate (e.g. creatine or glycocyamine; Reaction 1).

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mentioning

confidence: 94%

Trypanosoma cruzi Arginine Kinase Characterization and Cloning

Pereira

Alonso

Paveto

et al. 2000

Journal of Biological Chemistry

170

129

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“…In the latter case, glutamate induces oxidative stress by inhibiting a glutamate-cystine antiporter and subsequently promoting cystine efflux and/or blockade of cystine uptake. This results in the loss of intracellular glutathione and accumulation of intracellular ROS, and ultimately, oxidative cell death (Murphy and Miller, 1989;Pereira et al, 1997). Glutamate-induced oxidative cytotoxicity has been described in neuronal cell lines (Murphy and Miller, 1989;Froissard and Duval, 1994), primary neuronal cultures (Erdö et al, 1990) and oligodendrocytes (Oka et al, 1993).…”

Section: Introductionmentioning

confidence: 99%

Critical role of the JNK‐p53‐GADD45α apoptotic cascade in mediating oxidative cytotoxicity in hippocampal neurons

Choi

Kang

Fukui

et al. 2010

British J Pharmacology

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BACKGROUND AND PURPOSEGlutamate-induced oxidative stress plays a critical role in the induction of neuronal cell death in a number of disease states. We sought to determine the role of the c-Jun NH2-terminal kinase (JNK)-p53-growth arrest and DNA damage-inducible gene (GADD) 45a apoptotic cascade in mediating glutamate-induced oxidative cytotoxicity in hippocampal neuronal cells. EXPERIMENTAL APPROACHHT22 cells, a mouse hippocampal neuronal cell line, were treated with glutamate to induce oxidative stress in vitro. Kainic acid-induced oxidative damage to the hippocampus in rats was used as an in vivo model. The signalling molecules along the JNK-p53-GADD45a cascade were probed with various means to determine their contributions to oxidative neurotoxicity. KEY RESULTSTreatment of HT22 cells with glutamate increased the mRNA and protein levels of GADD45a, and these increases were suppressed by p53 knock-down. Knock-down of either p53 or GADD45a also prevented glutamate-induced cell death. Glutamate-induced p53 activation was preceded by accumulation of reactive oxygen species, and co-treatment with N-acetyl-cysteine prevented glutamate-induced p53 activation and GADD45a expression. Knock-down of MKK4 or JNK, or the presence of SP600125 (a JNK inhibitor), each inhibited glutamate-induced p53 activation and GADD45a expression. In addition, we also confirmed the involvement of GADD45a in mediating kainic acid-induced hippocampal oxidative neurotoxicity in vivo. CONCLUSIONS AND IMPLICATIONSActivation of the JNK-p53-GADD45a cascade played a critical role in mediating oxidative cytotoxicity in hippocampal neurons. Pharmacological inhibition of this signalling cascade may provide an effective strategy for neuroprotection.

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“…The resultant calcium influx leads to a rise in cGMP, ascribable to ⅐ NO-dependent activation of soluble guanylate cyclase (8). In mammalian cells, it has been postulated that ⅐ NO can mediate the regulation of caspase activity by the S-nitrosylation of critical thiol groups present in the active site (9,10), leading to inhibition of apoptotic death (11,12).…”

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confidence: 99%

l -Arginine-dependent suppression of apoptosis in Trypanosoma cruzi : Contribution of the nitric oxide and polyamine pathways

Piacenza

Peluffo

Radí

2001

Proc. Natl. Acad. Sci. U.S.A.

114

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Until recently, a capacity for apoptosis and synthesis of nitric oxide ( ⅐ NO) were viewed as exclusive to multicellular organisms. The existence of these processes in unicellular parasites was recently described, with their biological significance remaining to be elucidated. We have evaluated L-arginine metabolism in Trypanosoma cruzi in the context of human serum-induced apoptotic death. Apoptosis was evidenced by the induction of DNA fragmentation and the inhibition of [ 3 H]thymidine incorporation, which were inhibited by the caspase inhibitor Ac-Asp-Glu-Val-aspartic acid aldehyde (DEVD-CHO). In T. cruzi exposed to death stimuli, supplementation with L-arginine inhibited DNA fragmentation, restored [ 3 H]thymidine incorporation, and augmented parasite ⅐ NO production. These effects were inhibited by the ⅐ NO synthase inhibitor N -nitroarginine methyl ester (L-NAME). Exogenous ⅐ NO limited DNA fragmentation but did not restore proliferation rates. Because L-arginine is also a substrate for arginine decarboxylase (ADC), and its product agmatine is a precursor for polyamine synthesis, we evaluated the contribution of polyamines to limiting apoptosis. Addition of agmatine, putrescine, and the polyamines spermine and spermidine to T. cruzi sustained parasite proliferation and inhibited DNA fragmentation. Also, the ADC inhibitor difluoromethylarginine inhibited L-arginine-dependent restoration of parasite replication rates, while the protection from DNA fragmentation persisted. In aggregate, these results indicate that T. cruzi epimastigotes can undergo programmed cell death that can be inhibited by L-arginine by means of (i) a ⅐ NO synthase-dependent ⅐ NO production that suppresses apoptosis and (ii) an ADC-dependent production of polyamines that support parasite proliferation.

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Control of Trypanosoma cruzi Epimastigote Motility through the Nitric Oxide Pathway

Cited by 27 publications

References 15 publications

Trypanosoma cruzi Arginine Kinase Characterization and Cloning

Trypanosoma cruzi Arginine Kinase Characterization and Cloning

Critical role of the JNK‐p53‐GADD45α apoptotic cascade in mediating oxidative cytotoxicity in hippocampal neurons

l -Arginine-dependent suppression of apoptosis in Trypanosoma cruzi : Contribution of the nitric oxide and polyamine pathways

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