Hostname: page-component-78c5997874-8bhkd Total loading time: 0 Render date: 2024-11-09T22:39:21.980Z Has data issue: false hasContentIssue false
  • English
  • Français

Phenotypical characteristics, biochemical pathways, molecular targets and putative role of nitric oxide-mediated programmed cell death in Leishmania

Published online by Cambridge University Press:  03 October 2006

P. HOLZMULLER ,
R. BRAS-GONÇALVES  and
J.-L. LEMESRE
P. HOLZMULLER
Affiliation:
Equipe 1 Rôle biologique des facteurs d'excrétion-sécrétion des leishmanies: intérêt diagnostique et immunoprophylactique, UR 008 Pathogénie des Trypanosomatidae, IRD (Institut de Recherche pour le Développement), B.P. 64501, 911 avenue Agropolis, 34394 Montpellier cedex 5, France
R. BRAS-GONÇALVES
Affiliation:
Equipe 1 Rôle biologique des facteurs d'excrétion-sécrétion des leishmanies: intérêt diagnostique et immunoprophylactique, UR 008 Pathogénie des Trypanosomatidae, IRD (Institut de Recherche pour le Développement), B.P. 64501, 911 avenue Agropolis, 34394 Montpellier cedex 5, France
J.-L. LEMESRE
Affiliation:
Equipe 1 Rôle biologique des facteurs d'excrétion-sécrétion des leishmanies: intérêt diagnostique et immunoprophylactique, UR 008 Pathogénie des Trypanosomatidae, IRD (Institut de Recherche pour le Développement), B.P. 64501, 911 avenue Agropolis, 34394 Montpellier cedex 5, France
Get access Rights & Permissions [Opens in a new window]

Abstract

Nitric oxide (NO) has been demonstrated to be the principal effector molecule mediating intracellular killing of Leishmania, both in vitro and in vivo. We investigated the type of cell death process induced by NO for the intracellular amastigote stage of the protozoa Leishmania. Specific detection methods revealed a rapid and extensive cell death with morphological features of apoptosis in axenic amastigotes exposed to NO donors, in intracellular amastigotes inside in vitro – activated mouse macrophages and also in activated macrophages of regressive lesions in a leishmaniasis-resistant mouse model. We extended our investigations to the dog, a natural host-reservoir of Leishmania parasites, by demonstrating that co-incubation of infected macrophages with autologous lymphocytes derived from dogs immunised with purified excreted-secreted antigens of Leishmania resulted in a significant NO-mediated apoptotic cell death of intracellular amastigotes. From the biochemical point of view, NO-mediated Leishmania amastigotes apoptosis did not seem to be controlled by caspase activity as indicated by the lack of effect of cell permeable inhibitors of caspases and cysteine proteases, in contrast to specific proteasome inhibitors, such as lactacystin or calpain inhibitor I. Moreover, addition of the products of two NO molecular targets, cis-aconitase and glyceraldehyde-3-phosphate dehydrogenase, also had an inhibitory effect on the cell death induced by NO. Interestingly, activities of these two enzymes plus 6-phosphogluconate dehydrogenase, parasitic enzymes involved in both glycolysis and respiration processes, are overexpressed in amastigotes selected for their NO resistance. This review focuses on cell death of the intracellular stage of the pathogen Leishmania induced by nitrogen oxides and gives particular attention to the biochemical pathways and the molecular targets potentially involved. Questions about the role of Leishmania amastigotes NO-mediated apoptosis in the overall infection process are raised and discussed.

Keywords

Leishmanianitrogen oxidesprogrammed cell deathproteasomecalpainaconitase
Type
Research Article
Information
Parasitology , Volume 132 , Supplement S1: Programmed cell death and the protozoan parasite , March 2006 , pp. S19 - S32
Copyright
© 2006 Cambridge University Press

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

REFERENCES

Albina, J. E., Cui, S., Mateo, R. B. and Reichner, J. S. ( 1993). Nitric oxide-mediated apoptosis in murine peritoneal macrophages. Journal of Immunology 150, 5080–5085.Google Scholar
Alexander, J. and Russell, D. G. ( 1992). The interaction of Leishmania species with macrophages. Advances in Parasitology 31, 175–254.CrossRefGoogle Scholar
Al-Olayan, E. M., Williams, G. T. and Hurd, H. ( 2002). Apoptosis in the malaria protozoan, Plasmodium berghei: a possible mechanism for limiting intensity of infection in the mosquito. International Journal for Parasitology 32, 1133–1143.CrossRefGoogle Scholar
Aravind, L., Dixit, V. M. and Koonin, E. V. ( 2001). Apoptotic molecular machinery: vastly increased complexity in vertebrates revealed by genome comparisons. Science 291, 1279–1284.CrossRefGoogle Scholar
Arnoult, D., Akarid, K., Grodet, A., Petit, P. X., Estaquier, J. and Ameisen, J. C. ( 2002). On the evolution of programmed cell death: apoptosis of the unicellular eukaryote Leishmania major involves cysteine proteinase activation and mitochondrion permeabilization. Cell Death and Differentiation 9, 65–81.CrossRefGoogle Scholar
Ascenzi, P., Bocedi, A., Gentile, M., Visca, P. and Gradoni, L. ( 2004). Inactivation of parasite cysteine proteinases by the NO-donor 4-(phenylsulfonyl)-3-((2-(dimethylamino)ethyl)thio)-furoxan oxalate. Biochimica et Biophysica Acta 1703, 69–77.CrossRefGoogle Scholar
Barrett, M. P. ( 1997). The pentose phosphate pathway and parasitic protozoa. Parasitology Today 13, 11–16.CrossRefGoogle Scholar
Beinert, H. and Kennedy, M. C. ( 1993). Aconitase, a two-faced protein: enzyme and iron regulatory factor. FASEB Journal 7, 1442–1449.CrossRefGoogle Scholar
Bocedi, A., Gradoni, L., Menegatti, E. and Ascenzi, P. ( 2004). Kinetics of parasite cysteine proteinase inactivation by NO-donors. Biochemical and Biophysical Research Communications 315, 710–718.CrossRefGoogle Scholar
Bogdan, C. and Rollinghoff, M. ( 1998). The immune response to Leishmania: mechanisms of parasite control and evasion. International Journal for Parasitology 28, 121–134.CrossRefGoogle Scholar
Bosca, L. and Hortelano, S. ( 1999). Mechanisms of nitric oxide-dependent apoptosis: involvement of mitochondrial mediators. Cellular Signaling 11, 239–244.CrossRefGoogle Scholar
Boyd, C. and Cadenas, E. ( 2002). Nitric oxide and cell signaling pathways in mitochondrial-dependent apoptosis. Biological Chemistry 383, 411–423.CrossRefGoogle Scholar
Bras, M., Queenan, B. and Susin, S. A. ( 2005). Programmed cell death via mitochondria: different modes of dying. Biochemistry (Moscow) 70, 231–239.CrossRefGoogle Scholar
Brookes, P. S., Levonen, A. L., Shiva, S., Sarti, P. and Darley-Usmar, V. M. ( 2002). Mitochondria: regulators of signal transduction by reactive oxygen and nitrogen species. Free Radical Biology and Medicine 33, 755–764.CrossRefGoogle Scholar
Brown, G. C. and Borutaite, V. ( 2002). Nitric oxide inhibition of mitochondrial respiration and its role in cell death. Free Radical Biology and Medicine 33, 1440–1450.CrossRefGoogle Scholar
Brune, B. ( 2003). Nitric oxide: NO apoptosis or turning it ON? Cell Death and Differentiation 10, 864–869.Google Scholar
Brune, B., von Knethen, A. and Sandau, K. B. ( 1999). Nitric oxide (NO): an effector of apoptosis. Cell Death and Differentiation 6, 969–975.CrossRefGoogle Scholar
Carter, K. C., Alexander, J., Baillie, A. J. and Dolan, T. F. ( 1989). Visceral leishmaniasis: resistance to reinfection in the liver following chemotherapy in the BALB/c mouse. Experimental Parasitology 68, 375–381.CrossRefGoogle Scholar
Chowdhury, A. R., Mandal, S., Goswami, A., Ghosh, M., Mandal, L., Chakraborty, D., Ganguly, A., Tripathi, G., Mukhopadhyay, S., Bandyopadhyay, S. and Majumder, H. K. ( 2003). Dihydrobetulinic acid induces apoptosis in Leishmania donovani by targeting DNA topoisomerase I and II: implications in antileishmanial therapy. Molecular Medicine 9, 26–36.Google Scholar
Christensen, C. B., Jorgensen, L., Jensen, A. T., Gasim, S., Chen, M., Kharazmi, A., Theander, T. G. and Andresen, K. ( 2000). Molecular characterization of a Leishmania donovani cDNA clone with similarity to human 20S proteasome a-type subunit. Biochimica et Biophysica Acta 1500, 77–87.CrossRefGoogle Scholar
Clarke, P. G. ( 1990). Developmental cell death: morphological diversity and multiple mechanisms. Anatomy and Embryology 181, 195–213.CrossRefGoogle Scholar
Costa, N. J., Dahm, C. C., Hurrell, F., Taylor, E. R. and Murphy, M. P. ( 2003). Interactions of mitochondrial thiols with nitric oxide. Antioxidants and Redox Signaling 5, 291–305.CrossRefGoogle Scholar
Daiber, A., Frein, D., Namgaladze, D. and Ullrich, V. ( 2002). Oxidation and nitrosation in the nitrogen monoxide/superoxide system. Journal of Biological Chemistry 277, 11882–11888.CrossRefGoogle Scholar
Dardonville, C., Rinaldi, E., Hanau, S., Barrett, M. P., Brun, R. and Gilbert, I. H. ( 2003). Synthesis and biological evaluation of substrate-based inhibitors of 6-phosphogluconate dehydrogenase as potential drugs against African trypanosomiasis. Bioorganic and Medicinal Chemistry 11, 3205–3214.CrossRefGoogle Scholar
Das, M., Mukherjee, S. B. and Shaha, C. ( 2001). Hydrogen peroxide induces apoptosis-like death in Leishmania donovani promastigotes. Journal of Cell Science 114, 2461–2469.Google Scholar
Debrabant, A., Lee, N., Bertholet, S., Duncan, R. and Nakhasi, H. L. ( 2003). Programmed cell death in trypanosomatids and other unicellular organisms. International Journal for Parasitology 33, 257–267.CrossRefGoogle Scholar
Debrabant, A. and Nakhasi, H. ( 2003). Programmed cell death in trypanosomatids: is it an altruistic mechanism for survival of the fittest? Kinetoplastid Biology and Disease 25, 7.Google Scholar
de Freitas Balanco, J. M., Moreira, M. E., Bonomo, A., Bozza, P. T., Amarante-Mendes, G., Pirmez, C. and Barcinski, M. A. ( 2001). Apoptotic mimicry by an obligate intracellular parasite downregulates macrophage microbicidal activity. Current Biology 11, 1870–1873.CrossRefGoogle Scholar
Denise, H., McNeil, K., Brooks, D. R., Alexander, J., Coombs, G. H. and Mottram, J. C. ( 2003). Expression of multiple CPB genes encoding cysteine proteases is required for Leishmania mexicana virulence in vivo. Infection and Immunity 71, 3190–3195.CrossRefGoogle Scholar
Dimmeler, S., Haendeler, J., Nehls, M. and Zeiher, A. M. ( 1997). Suppression of apoptosis by nitric oxide via inhibition of interleukin-1beta-converting enzyme (ICE)-like and cysteine protease protein (CPP)-32-like proteases. Journal of Experimental Medicine 185, 601–607.CrossRefGoogle Scholar
DosReis, G. A. and Barcinski, M. A. ( 2001). Apoptosis and parasitism: from the parasite to the host immune response. Advances in Parasitology 49, 133–161.CrossRefGoogle Scholar
Espey, M. G., Thomas, D. D., Miranda, K. M. and Wink, D. A. ( 2002). Focusing of nitric oxide mediated nitrosation and oxidative nitrosylation as a consequence of reaction with superoxide. Proceedings of the National Academy of Sciences, USA 99, 11127–11132.CrossRefGoogle Scholar
Eu, J. P., Liu, L., Zeng, M. and Stamler, J. S. ( 2000). An apoptotic model for nitrosative stress. Biochemistry 39, 1040–1047.CrossRefGoogle Scholar
Feger, F., Ferry-Dumazet, H., Mamani Matsuda, M., Bordenave, J., Dupouy, M., Nussler, A. K., Arock, M., Devevey, L., Nafziger, J., Guillosson, J. J., Reiffers, J. and Mossalayi, M. D. ( 2001). Role of iron in tumor cell protection from the pro-apoptotic effect of nitric oxide. Cancer Research 61, 5289–5294.Google Scholar
Frame, M. J., Mottram, J. C. and Coombs, G. H. ( 2000). Analysis of the roles of cysteine proteinases of Leishmania mexicana in the host-parasite interaction. Parasitology 121, 367–377.CrossRefGoogle Scholar
Gallego, C., Estevez, A. M., Farez, E., Ruiz-Perez, L. M. and Gonzalez-Pacanowska, D. ( 2005). Overexpression of AP endonuclease protects Leishmania major cells against methotrexate induced DNA fragmentation and hydrogen peroxide. Molecular and Biochemical Parasitology 141, 191–197.CrossRefGoogle Scholar
Green, D. R. ( 2000). Apoptotic pathways: paper wraps stone blunts scissors. Cell 102, 1–4.CrossRefGoogle Scholar
Green, D. R., Knight, R. A., Melino, G., Finazzi-Agro', A. and Orrenius, S. ( 2004). Ten years of publication in cell death. Cell Death and Differentiation 11, 2–3.CrossRefGoogle Scholar
Green, S. J., Crawford, R. M., Hockmeyer, J. T., Meltzer, M. S. and Nacy, C. A. ( 1990). Leishmania major amastigotes initiate the L-arginine-dependent killing mechanism in IFN-gamma-stimulated macrophages by induction of tumor necrosis factor-alpha. Journal of Immunology 145, 4290–4297.Google Scholar
Gross, A., McDonnell, J. M. and Korsmeyer, S. J. ( 1999). BCL-2 family members and the mitochondria in apoptosis. Genes and Development 13, 1899–1911.CrossRefGoogle Scholar
Hengartner, M. O. ( 2000). The biochemistry of apoptosis. Nature 407, 770–776.CrossRefGoogle Scholar
Henkart, P. A. and Grinstein, S. ( 1996). Apoptosis: mitochondria resurrected? Journal of Experimental Medicine 183, 1293–1295.Google Scholar
Heussler, V. T., Kuenzi, P. and Rottenberg, S. ( 2001). Inhibition of apoptosis by intracellular protozoan parasites. International Journal for Parasitology 31, 1166–1176.CrossRefGoogle Scholar
Holzmuller, P., Cavaleyra, M., Moreaux, J., Kovacic, R., Vincendeau, P., Papierok, G. and Lemesre, J. L. ( 2005 a). Lymphocytes of dogs immunised with purified excreted-secreted antigens of Leishmania infantum co-incubated with Leishmania infected macrophages produce IFN gamma resulting in nitric oxide-mediated amastigote apoptosis. Veterinary Immunology and Immunopathology 106, 247–257.Google Scholar
Holzmuller, P., Hide, M., Sereno, D. and Lemesre, J. L. ( 2006). Leishmania infantum amastigotes resistant to nitric oxide cytotoxicity: Impact on in vitro parasite developmental cycle and metabolic enzyme activities. Infection, Genetics and Evolution 6, 187–197.CrossRefGoogle Scholar
Holzmuller, P., Sereno, D., Cavaleyra, M., Mangot, I., Daulouede, S., Vincendeau, P. and Lemesre, J. L. ( 2002). Nitric oxide-mediated proteasome-dependent oligonucleosomal DNA fragmentation in Leishmania amazonensis amastigotes. Infection and Immunity 70, 3727–3735.CrossRefGoogle Scholar
Holzmuller, P., Sereno, D. and Lemesre, J. L. ( 2005 b). Lower nitric oxide susceptibility of trivalent antimony-resistant amastigotes of Leishmania infantum. Antimicrobial Agents and Chemotherapy 49, 4406–4409.Google Scholar
Hortelano, S., Alvarez, A. M. and Bosca, L. ( 1999). Nitric oxide induces tyrosine nitration and release of cytochrome c preceding an increase of mitochondrial transmembrane potential in macrophages. FASEB Journal 13, 2311–2317.CrossRefGoogle Scholar
Hortelano, S., Dallaporta, B., Zamzami, N., Hirsch, T., Susin, S. A., Marzo, I., Bosca, L. and Kroemer, G. ( 1997). Nitric oxide induces apoptosis via triggering mitochondrial permeability transition. FEBS Letters 410, 373–377.CrossRefGoogle Scholar
Hurd, H., Carter, V. and Nacer, A. ( 2005). Interactions between malaria and mosquitoes: the role of apoptosis in parasite establishment and vector response to infection. Current Topics Microbiology and Immunology 289, 185–217.CrossRefGoogle Scholar
Jaffrey, S. R., Erdjument-Bromage, H., Ferris, C. D., Tempst, P. and Snyder, S. H. ( 2001). Protein S-nitrosylation: a physiological signal for neuronal nitric oxide. Nature Cell Biology 3, 193–197.CrossRefGoogle Scholar
Jayanarayan, K. G. and Dey, C. S. ( 2004). Altered expression, polymerisation and cellular distribution of alpha-/beta-tubulins and apoptosis-like cell death in arsenite resistant Leishmania donovani promastigotes. International Journal for Parasitology 34, 915–925.CrossRefGoogle Scholar
Jayanarayan, K. G. and Dey, C. S. ( 2005). Altered tubulin dynamics, localization and post-translational modifications in sodium arsenite resistant Leishmania donovani in response to paclitaxel, trifluralin and a combination of both and induction of apoptosis-like cell death. Parasitology 131, 215–230.CrossRefGoogle Scholar
Johnson, D. E. ( 2000). Noncaspase proteases in apoptosis. Leukemia 14, 1695–1703.CrossRefGoogle Scholar
Kerr, J. F., Wyllie, A. H. and Currie, A. R. ( 1972). Apoptosis: a basic biological phenomenon with wide-ranging implications in tissue kinetics. British Journal of Cancer 26, 239–257.CrossRefGoogle Scholar
Lee, N., Bertholet, S., Debrabant, A., Muller, J., Duncan, R. and Nakhasi, H. L. ( 2002). Programmed cell death in the unicellular protozoan parasite Leishmania. Cell Death and Differentiation 9, 53–64.CrossRefGoogle Scholar
Le Goffe, C., Vallette, G., Charrier, L., Candelon, T., Bou-Hanna, C., Bouhours, J. F. and Laboisse, C. L. ( 2002). Metabolic control of resistance of human epithelial cells to H2O2 and NO stresses. Biochemical Journal 364, 349–359.CrossRefGoogle Scholar
Lemesre, J. L. ( 1994). Methods for the culture in vitro of different stages of tissue parasites, International Publication WO 94/26899.
Lemesre, J. L., Holzmuller, P., Cavaleyra, M., Goncalves, R. B., Hottin, G. and Papierok, G. ( 2005). Protection against experimental visceral leishmaniasis infection in dogs immunized with purified excreted secreted antigens of Leishmania infantum promastigotes. Vaccine 23, 2825–2840.CrossRefGoogle Scholar
Lemesre, J. L., Sereno, D., Daulouede, S., Veyret, B., Brajon, N. and Vincendeau, P. ( 1997). Leishmania spp.: nitric oxide-mediated metabolic inhibition of promastigote and axenically grown amastigote forms. Experimental Parasitology 86, 58–68.Google Scholar
Lindoso, J. A., Cotrim, P. C. and Goto, H. ( 2004). Apoptosis of Leishmania (Leishmania) chagasi amastigotes in hamsters infected with visceral leishmaniasis. International Journal for Parasitology 34, 1–4.CrossRefGoogle Scholar
Liu, L. and Stamler, J. S. ( 1999). NO: an inhibitor of cell death. Cell Death and Differentiation 6, 937–942.CrossRefGoogle Scholar
Mallinson, D. J. and Coombs, G. H. ( 1989). Interaction of Leishmania metacyclics with macrophages. International Journal for Parasitology 19, 647–656.CrossRefGoogle Scholar
Marquis, J. F., Hardy, I. and Olivier, M. ( 2005). Resistance mechanism development to the topoisomerase-I inhibitor Hoechst 33342 by Leishmania donovani. Parasitology 131, 197–206.CrossRefGoogle Scholar
Martinou, J. C. and Green, D. R. ( 2001). Breaking the mitochondrial barrier. Nature Reviews – Molecular Cell Biology 2, 63–67.CrossRefGoogle Scholar
Mauel, J. and Ransijn, A. ( 1997). Leishmania spp.: mechanisms of toxicity of nitrogen oxidation products. Experimental Parasitology 87, 98–111.Google Scholar
McGinnis, K. M., Gnegy, M. E., Park, Y. H., Mukerjee, N. and Wang, K. K. ( 1999). Procaspase-3 and poly(ADP)ribose polymerase (PARP) are calpain substrates. Biochemical and Biophysical Research Communications 263, 94–99.CrossRefGoogle Scholar
Mehta, A. and Shaha, C. ( 2004). Apoptotic death in Leishmania donovani promastigotes in response to respiratory chain inhibition: complex II inhibition results in increased pentamidine cytotoxicity. Journal of Biological Chemistry 279, 11798–11813.CrossRefGoogle Scholar
Merlen, T., Sereno, D., Brajon, N., Rostand, F. and Lemesre, J. L. ( 1999). Leishmania spp: completely defined medium without serum and macromolecules (CDM/LP) for the continuous in vitro cultivation of infective promastigote forms. American Journal of Tropical Medicine and Hygiene 60, 41–50.CrossRefGoogle Scholar
Mittra, B., Saha, A., Chowdhury, A. R., Pal, C., Mandal, S., Mukhopadhyay, S., Bandyopadhyay, S. and Majumder, H. K. ( 2000). Luteolin, an abundant dietary component is a potent anti-leishmanial agent that acts by inducing topoisomerase II-mediated kinetoplast DNA cleavage leading to apoptosis. Molecular Medicine 6, 527–541.Google Scholar
Moncada, S. and Erusalimsky, J. D. ( 2002). Does nitric oxide modulate mitochondrial energy generation and apoptosis? Nature Reviews – Molecular Cell Biology 3, 214–220.Google Scholar
Moreira, M. E., Del Portillo, H. A., Milder, R. V., Balanco, J. M. and Barcinski, M. A. ( 1996). Heat shock induction of apoptosis in promastigotes of the unicellular organism Leishmania (Leishmania) amazonensis. Journal of Cellular Physiology 167, 305–313.3.0.CO;2-6>CrossRefGoogle Scholar
Mottram, J. C., Brooks, D. R. and Coombs, G. H. ( 1998). Roles of cysteine proteinases of trypanosomes and Leishmania in host-parasite interactions. Current Opinion in Microbiology 1, 455–460.CrossRefGoogle Scholar
Mottram, J. C., Coombs, G. H. and Alexander, J. ( 2004). Cysteine peptidases as virulence factors of Leishmania. Current Opinion in Microbiology 7, 375–381.CrossRefGoogle Scholar
Mottram, J. C., Helms, M. J., Coombs, G. H. and Sajid, M. ( 2003). Clan CD cysteine peptidases of parasitic protozoa. Trends in Parasitology 19, 182–187.CrossRefGoogle Scholar
Mottram, J. C., Souza, A. E., Hutchison, J. E., Carter, R., Frame, M. J. and Coombs, G. H. ( 1996). Evidence from disruption of the lmcpb gene array of Leishmania mexicana that cysteine proteinases are virulence factors. Proceedings of the National Academy of Sciences, USA 93, 6008–6013.CrossRefGoogle Scholar
Mukherjee, S. B., Das, M., Sudhandiran, G. and Shaha, C. ( 2002). Increase in cytosolic Ca2+ levels through the activation of non-selective cation channels induced by oxidative stress causes mitochondrial depolarization leading to apoptosis-like death in Leishmania donovani promastigotes. Journal of Biological Chemistry 277, 24717–24727.CrossRefGoogle Scholar
Mukkada, A. J., Meade, J. C., Glaser, T. A. and Bonventre, P. F. ( 1985). Enhanced metabolism of Leishmania donovani amastigotes at acid pH: an adaptation for intracellular growth. Science 229, 1099–1101.CrossRefGoogle Scholar
Nguewa, P. A., Fuertes, M. A., Iborra, S., Najajreh, Y., Gibson, D., Martinez, E., Alonso, C. and Perez, J. M. ( 2005). Water soluble cationic trans-platinum complexes which induce programmed cell death in the protozoan parasite Leishmania infantum. Journal of Inorganic Biochemistry 99, 727–736.CrossRefGoogle Scholar
Nguewa, P. A., Fuertes, M. A., Valladares, B., Alonso, C. and Perez, J. M. ( 2004). Programmed cell death in trypanosomatids: a way to maximize their biological fitness? Trends in Parasitology 20, 375–380.Google Scholar
Nicholson, D. W. and Thornberry, N. A. ( 2003). Apoptosis. Life and death decisions. Science 299, 214–215.Google Scholar
Noel, W., Raes, G., Hassanzadeh Ghassabeh, G., De Baetselier, P. and Beschin, A. ( 2004). Alternatively activated macrophages during parasite infections. Trends in Parasitology 20, 126–133.CrossRefGoogle Scholar
Orlowski, R. Z. ( 1999). The role of the ubiquitin-proteasome pathway in apoptosis. Cell Death and Differentiation 6, 303–313.CrossRefGoogle Scholar
Panaro, M. A., Acquafredda, A., Lisi, S., Lofrumento, D. D., Trotta, T., Satalino, R., Saccia, M., Mitolo, V. and Brandonisio, O. ( 1999). Inducible nitric oxide synthase and nitric oxide production in Leishmania infantum-infected human macrophages stimulated with interferon-gamma and bacterial lipopolysaccharide. International Journal of Clinical and Laboratory Research 29, 122–127.CrossRefGoogle Scholar
Paris, C., Loiseau, P. M., Bories, C. and Breard, J. ( 2004). Miltefosine induces apoptosis-like death in Leishmania donovani promastigotes. Antimicrobial Agents and Chemotherapy 48, 852–859.CrossRefGoogle Scholar
Paugam, A., Bulteau, A. L., Dupouy-Camet, J., Creuzet, C. and Friguet, B. ( 2003). Characterization and role of protozoan parasite proteasomes. Trends in Parasitology 19, 55–59.CrossRefGoogle Scholar
Radi, R., Cassina, A. and Hodara, R. ( 2002). Nitric oxide and peroxynitrite interactions with mitochondria. Biological Chemistry 383, 401–409.CrossRefGoogle Scholar
Radons, J., Heller, B., Burkle, A., Hartmann, B., Rodriguez, M. L., Kroncke, K. D., Burkart, V. and Kolb, H. ( 1994). Nitric oxide toxicity in islet cells involves poly(ADP-ribose) polymerase activation and concomitant NAD+ depletion. Biochemical and Biophysical Research Communications 199, 1270–1277.CrossRefGoogle Scholar
Reed, J. C. ( 1994). Bcl-2 and the regulation of programmed cell death. Journal of Cell Biology 124, 1–6.CrossRefGoogle Scholar
Richter, C., Gogvadze, V., Schlapbach, R., Schweizer, M. and Schlegel, J. ( 1994). Nitric oxide kills hepatocytes by mobilizing mitochondrial calcium. Biochemical and Biophysical Research Communications 205, 1143–1150.CrossRefGoogle Scholar
Robertson, C. D. ( 1999). The Leishmania mexicana proteasome. Molecular and Biochemical Parasitology 103, 49–60.CrossRefGoogle Scholar
Sacks, D. and Noben-Trauth, N. ( 2002). The immunology of susceptibility and resistance to Leishmania major in mice. Nature Reviews – Immunology 2, 845–858.CrossRefGoogle Scholar
Salvati, L., Mattu, M., Colasanti, M., Scalone, A., Venturini, G., Gradoni, L. and Ascenzi, P. ( 2001). NO donors inhibit Leishmania infantum cysteine proteinase activity. Biochimica et Biophysica Acta 1545, 357–366.CrossRefGoogle Scholar
Sarih, M., Souvannavong, V. and Adam, A. ( 1993). Nitric oxide synthase induces macrophage death by apoptosis. Biochemical and Biophysical Research Communications 191, 503–508.CrossRefGoogle Scholar
Scott, P. ( 1991). IFN-gamma modulates the early development of Th1 and Th2 responses in a murine model of cutaneous leishmaniasis. Journal of Immunology 147, 3149–3155.Google Scholar
Selvapandiyan, A., Debrabant, A., Duncan, R., Muller, J., Salotra, P., Sreenivas, G., Salisbury, J. L. and Nakhasi, H. L. ( 2004). Centrin gene disruption impairs stage-specific basal body duplication and cell cycle progression in Leishmania. Journal of Biological Chemistry 279, 25703–25710.CrossRefGoogle Scholar
Selzer, P. M., Pingel, S., Hsieh, I., Ugele, B., Chan, V. J., Engel, J. C., Bogyo, M., Russell, D. G., Sakanari, J. A. and Mckerrow, J. H. ( 1999). Cysteine protease inhibitors as chemotherapy: lessons from a parasite target. Proceedings of the National Academy of Sciences, USA 96, 11015–11022.CrossRefGoogle Scholar
Sen, N., Das, B. B., Ganguly, A., Mukherjee, T., Bandyopadhyay, S. and Majumder, H. K. ( 2004 a). Camptothecin-induced imbalance in intracellular cation homeostasis regulates programmed cell death in unicellular hemoflagellate Leishmania donovani. Journal of Biological Chemistry 279, 52366–52375.Google Scholar
Sen, N., Das, B. B., Ganguly, A., Mukherjee, T., Tripathi, G., Bandyopadhyay, S., Rakshit, S., Sen, T. and Majumder, H. K. ( 2004 b). Camptothecin induced mitochondrial dysfunction leading to programmed cell death in unicellular hemoflagellate Leishmania donovani. Cell Death and Differentiation 11, 924–936.Google Scholar
Sereno, D., Holzmuller, P., Mangot, I., Cuny, G., Ouaissi, A. and Lemesre, J. L. ( 2001). Antimonial-mediated DNA fragmentation in Leishmania infantum amastigotes. Antimicrobial Agents and Chemotherapy 45, 2064–2069.CrossRefGoogle Scholar
Sereno, D. and Lemesre, J. L. ( 1997). Axenically cultured amastigote forms as an in vitro model for investigation of antileishmanial agents. Antimicrobial Agents and Chemotherapy 41, 972–976.Google Scholar
Singh, G., Jayanarayan, K. G. and Dey, C. S. ( 2005). Novobiocin induces apoptosis-like cell death in topoisomerase II over-expressing arsenite resistant Leishmania donovani. Molecular and Biochemical Parasitology 141, 57–69.CrossRefGoogle Scholar
Sisto, M., Brandonisio, O., Panaro, M. A., Acquafredda, A., Leogrande, D., Fasanella, A., Trotta, T., Fumarola, L. and Mitolo, V. ( 2001). Inducible nitric oxide synthase expression in Leishmania-infected dog macrophages. Comparative Immunology, Microbiology and Infectious Diseases 24, 247–254.CrossRefGoogle Scholar
Sousa-Franco, J., Araujo-Mendes, E., Silva-Jardim, I., L-Santos, J., Faria, D. R., Dutra, W. O. and Horta, M. D. ( 2005). Infection-induced respiratory burst in BALB/c macrophages kills Leishmania guyanensis amastigotes through apoptosis: possible involvement in resistance to cutaneous leishmaniasis. Microbes and Infection 8, 390–400.Google Scholar
Sperandio, S., De Belle, I. and Bredesen, D. E. ( 2000). An alternative, nonapoptotic form of programmed cell death. Proceedings of the National Academy of Sciences, USA 97, 14376–14381.CrossRefGoogle Scholar
Stamler, J. S., Lamas, S. and Fang, F. C. ( 2001). Nitrosylation. the prototypic redox-based signaling mechanism. Cell 106, 675–683.CrossRefGoogle Scholar
Sudhandiran, G. and Shaha, C. ( 2003). Antimonial-induced increase in intracellular Ca2+ through non-selective cation channels in the host and the parasite is responsible for apoptosis of intracellular Leishmania donovani amastigotes. Journal of Biological Chemistry 278, 25120–25132.CrossRefGoogle Scholar
Szabo, C. and Salzman, A. L. ( 1995). Endogenous peroxynitrite is involved in the inhibition of mitochondrial respiration in immuno-stimulated J774.2 macrophages. Biochemical and Biophysical Research Communications 209, 739–743.CrossRefGoogle Scholar
Szallies, A., Kubata, B. K. and Duszenko, M. ( 2002). A metacaspase of Trypanosoma brucei causes loss of respiration competence and clonal death in the yeast Saccharomyces cerevisiae. FEBS Letters 517, 144–150.CrossRefGoogle Scholar
Tavares, J., Ouaissi, A., Lin, P. K., Tomas, A. and Cordeiro-Da-Silva, A. ( 2005). Differential effects of polyamine derivative compounds against Leishmania infantum promastigotes and axenic amastigotes. International Journal for Parasitology 35, 637–646.CrossRefGoogle Scholar
Thomas, D. D., Miranda, K. M., Espey, M. G., Citrin, D., Jourd'heuil, D., Paolocci, N., Hewett, S. J., Colton, C. A., Grisham, M. B., Feelisch, M. and Wink, D. A. ( 2002). Guide for the use of nitric oxide (NO) donors as probes of the chemistry of NO and related redox species in biological systems. Methods in Enzymology 359, 84–105.CrossRefGoogle Scholar
Uren, A. G., O'Rourke, K., Aravind, L. A., Pisabarro, M. T., Seshagiri, S., Koonin, E. V. and Dixit, V. M. ( 2000). Identification of paracaspases and metacaspases: two ancient families of caspase-like proteins, one of which plays a key role in MALT lymphoma. Molecular Cell 6, 961–917.CrossRefGoogle Scholar
Vergnes, B., Sereno, D., Madjidian-Sereno, N., Lemesre, J. L. and Ouaissi, A. ( 2002). Cytoplasmic SIR2 homologue overexpression promotes survival of Leishmania parasites by preventing programmed cell death. Gene 296, 139–150.CrossRefGoogle Scholar
Vergnes, B., Vanhille, L., Ouaissi, A. and Sereno, D. ( 2005). Stage-specific antileishmanial activity of an inhibitor of SIR2 histone deacetylase. Acta Tropica 94, 107–115.CrossRefGoogle Scholar
Verma, N. K. and Dey, C. S. ( 2004). Possible mechanism of miltefosine-mediated death of Leishmania donovani. Antimicrobial Agents and Chemotherapy 48, 3010–3015.CrossRefGoogle Scholar
Volbracht, C., Chua, B. T., Ng, C. P., Bahr, B. A., Hong, W. and Li, P. ( 2005). The critical role of calpain versus caspase activation in excitotoxic injury induced by nitric oxide. Journal of Neurochemistry 93, 1280–1292.CrossRefGoogle Scholar
Vouldoukis, I., Drapier, J. C., Nussler, A. K., Tselentis, Y., Da Silva, O. A., Gentilini, M., Mossalayi, D. M., Monjour, L. and Dugas, B. ( 1996). Canine visceral leishmaniasis: successful chemotherapy induces macrophage antileishmanial activity via the L-arginine nitric oxide pathway. Antimicrobial Agents and Chemotherapy 40, 253–256.Google Scholar
Wanderley, J. L., Benjamin, A., Real, F., Bonomo, A., Moreira, M. E. and Barcinski, M. A. ( 2005). Apoptotic mimicry: an altruistic behavior in host/Leishmania interplay. Brazilian Journal of Medical and Biological Research 38, 807–812.CrossRefGoogle Scholar
Welburn, S. C., Barcinski, M. A. and Williams, G. T. ( 1997). Programmed cell death in trypanosomatids. Parasitology Today 13, 22–26.CrossRefGoogle Scholar
Welburn, S. C. and Murphy, N. B. ( 1998). Prohibitin and RACK homologues are up-regulated in trypanosomes induced to undergo apoptosis and in naturally occurring terminally differentiated forms. Cell Death and Differentiation 5, 615–622.CrossRefGoogle Scholar
Zamzami, N. and Kroemer, G. ( 2001). The mitochondrion in apoptosis: how Pandora's box opens. Nature Reviews – Molecular Cell Biology 2, 67–71.CrossRefGoogle Scholar
Zangger, H., Mottram, J. C. and Fasel, N. ( 2002). Cell death in Leishmania induced by stress and differentiation: programmed cell death or necrosis? Cell Death and Differentiation 9, 1126–1139.Google Scholar
Zhang, J. and Snyder, S. H. ( 1993). Purification of a nitric oxide-stimulated ADP-ribosylated protein using biotinylated beta-nicotinamide adenine dinucleotide. Biochemistry 32, 2228–2233.CrossRefGoogle Scholar