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Effects of protein kinase inhibitors on the in vitro growth of Babesia bovis

Published online by Cambridge University Press:  24 February 2006

S. BORK ,
S. DAS ,
K. OKUBO ,
N. YOKOYAMA  and
I. IGARASHI
S. BORK
Affiliation:
National Research Center for Protozoan Diseases, Obihiro University of Agriculture and Veterinary Medicine, Inada-cho, Obihiro, Hokkaido 080-8555, Japan
S. DAS
Affiliation:
National Research Center for Protozoan Diseases, Obihiro University of Agriculture and Veterinary Medicine, Inada-cho, Obihiro, Hokkaido 080-8555, Japan Institute of Animal Health and Veterinary Biologicals, Animal Research Development Department, Kolkata, Government of West Bengal, India
K. OKUBO
Affiliation:
National Research Center for Protozoan Diseases, Obihiro University of Agriculture and Veterinary Medicine, Inada-cho, Obihiro, Hokkaido 080-8555, Japan
N. YOKOYAMA
Affiliation:
National Research Center for Protozoan Diseases, Obihiro University of Agriculture and Veterinary Medicine, Inada-cho, Obihiro, Hokkaido 080-8555, Japan
I. IGARASHI
Affiliation:
National Research Center for Protozoan Diseases, Obihiro University of Agriculture and Veterinary Medicine, Inada-cho, Obihiro, Hokkaido 080-8555, Japan
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Abstract

Staurosporine, Ro-31-7549, and KN-93, which are inhibitors of serine/threonine protein kinase, protein kinase C, and calcium-modulin kinase, respectively, were tested for their effects on the in vitro growth of Babesia bovis. Staurosporine was the most effective inhibitor, completely clearing the parasitaemia as early as the first day of exposure at a concentration of 100 μM. Moreover, staurosporine caused a significant increase in the percentage of extracellular merozoites, most likely due to the inhibition of erythrocyte invasion by the parasite. Although 5 mM Ro-31-7549 and KN-93 had a suppressive action, this was not enough to destroy the parasite. Interestingly, concentrations of 0·5 to 5 mM KN-93 influenced the parasitic development within the infected erythrocytes. The present study suggests that B. bovis requires, to a certain extent, the phosphorylations mediated by parasite- or host erythrocyte-protein kinases, in particular, for the processes of successful invasion of erythrocytes and intraerythrocytic development.

Keywords

staurosporineRo-31-7549KN-93Babesia bovisin vitro cultivation
Type
Research Article
Information
Parasitology , Volume 132 , Issue 6 , June 2006 , pp. 775 - 779
Copyright
2006 Cambridge University Press

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References

REFERENCES

Becker, S. and Jaffe, C. L. ( 1997). Effect of protein kinase inhibitors on the growth, morphology, and infectivity of Leishmania promastigotes. Parasitology Research 83, 273–280.CrossRefGoogle Scholar
Berg, T. ( 2003). The vascular response to the K+ channel inhibitor 4-aminopyridine in hypertensive rats. European Journal of Pharmacology 466, 301–310.CrossRefGoogle Scholar
Bork, S., Yokoyama, N., Matsuo, T., Claveria, F. G., Fujisaki, K. and Igarashi, I. ( 2003 a). Growth inhibitory effect of triclosan on equine and bovine Babesia parasites. American Journal of Tropical Medicine and Hygiene 68, 334–340.Google Scholar
Bork, S., Yokoyama, N., Matsuo, T., Claveria, F. G., Fujisaki, K. and igarashi, I. ( 2003 b). Clotrimazole, ketoconazole, and clodinafop-propargyl as potent growth inhibitors of equine Babesia parasites during in vitro culture. Journal of Parasitology 89, 604–606.Google Scholar
Bork, S., Yokoyama, N., Ikehara, Y., Kumar, S., Sugimoto, C. and Igarashi, I. ( 2004 a). Growth inhibitory effect of heparin on Babesia parasites. Antimicrobial Agents and Chemotherapy 48, 236–241.Google Scholar
Bork, S., Okamura, M., Boonchit, S., Hirata, H., Yokoyama, N. and Igarashi, I. ( 2004 b). Identification of Babesia bovis L-lactate dehydrogenase as a chemotherapeutical target against bovine babesiosis. Molecular and Biochemical Parasitology 136, 165–172.Google Scholar
Bork, S., Okamura, M., Matsuo, T., Kumar, S., Yokoyama, N. and Igarashi, I. ( 2005). Host serum modifies the drug susceptibility of Babesia bovis in vitro. Parasitology 130, 489–492.CrossRefGoogle Scholar
Bray, D. ( 1990). Intracellular signaling as a parallel distributed process. Journal of Theoretical Biology 143, 215–231.CrossRefGoogle Scholar
Dluzewski, A. R. and Garcia, C. R. ( 1996). Inhibition of invasion and intraerythrocytic development of Plasmodium falciparum by kinase inhibitors. Experientia 52, 621–623.CrossRefGoogle Scholar
Doerig, C. ( 2004). Protein kinases as targets for anti-parasitic chemotherapy. Biochimica et Biophysica Acta 1697, 155–168.CrossRefGoogle Scholar
Flawia, M. M., Tellez-Inon, M. T. and Torres, H. N. ( 1997). Signal transduction mechanisms in Trypanosoma cruzi. Parasitology Today 13, 30–33.CrossRefGoogle Scholar
Fulop, T., Larbi, A. and Douziech, N. ( 2003). Insulin receptor and ageing. Pathologie-biologie 51, 574–580.CrossRefGoogle Scholar
Gazarini, M. L. and Garcia, C. R. ( 2003). Interruption of the blood-stage cycle of the malaria parasite, Plasmodium chabaudi, by protein tyrosine kinase inhibitors. Brazilian Journal of Medical and Biological Research 36, 1465–1469.CrossRefGoogle Scholar
Hashimoto, Y., Togo, M., Sato, H., Hashimoto, N., Watanabe, T., Kurokawa, K. and Nakahara, K. ( 1997). Characteristics of protein kinase C-independent exocytosis in human platelets. Thrombosis Research 88, 51–58.CrossRefGoogle Scholar
Homer, M. J., Aguilar-Delfin, I., Telford, S. R. 3rd, Krause, P. J. and Persing, D. H. ( 2000). Babesiosis. Clinical Microbiology Review 3, 451–469.CrossRefGoogle Scholar
Karin, M. ( 1991). Signal transduction and gene control. Current Opinion in Cell Biology 3, 467–473.CrossRefGoogle Scholar
Komuro, I. ( 2001). Molecular mechanism of cardiac hypertrophy and development. Japanese Circulation Journal 655, 353–358.CrossRefGoogle Scholar
Kuttler, K. L. ( 1988). Worldwide impact of babesiosis. In Babesiosis of Domestic Animals and Man ( ed. Ristic, M.), pp. 2–22. CRC Press Inc., Boca Raton, Florida, USA.
Levine, N. D. ( 1988). The Protozoan Phylum Apicomplexa. Vol. 2. CRC Press, Boca Raton, Florida, USA.
Malaquias, A. T. and Oliveira, M. M. ( 1999). Phospholipid signaling pathways in Trypanosoma cruzi growth control. Acta Tropica 73, 93–108.CrossRefGoogle Scholar
Ray, A., Quade, J., Carson, C. A. and Ray, B. K. ( 1990). Calcium-dependent protein phosphorylation in Babesia bovis and its role in growth regulation. Journal of Parasitology 76, 153–161.CrossRefGoogle Scholar
Russello, S. V. and Shore, S. K. ( 2004). SRC in human carcinogenesis. Frontiers in Bioscience 9, 139–144.Google Scholar
Sam-Yellowe, T. Y. ( 1996). Rhoptry organelles of the apicomplexa: their role in host cell invasion and intracellular survival. Parasitology Today 12, 308–316.CrossRefGoogle Scholar
Sancelme, M., Fabre, S. and Prudhomme, M. ( 1994). Antimicrobial activities of indolocarbazole and bis-indole protein kinase C inhibitors. Journal of Antibiotics 47, 792–798.CrossRefGoogle Scholar
Silva-Neto, M. A., Atella, G. C. and Shahabuddin, M. ( 2002). Inhibition of Ca2+/calmodulin-dependent protein kinase blocks morphological differentiation of Plasmodium gallinaceum zygotes to ookinetes. Journal of Biological Chemistry 277, 14085–14091.CrossRefGoogle Scholar
Sumi, M., Kiuchi, K., Ishikawa, T., Ishii, A., Hagiwara, M., Nagatsu, T. and Hidaka, H. ( 1991). The newly synthesized selective Ca2+/calmodulin-dependent protein kinase II inhibitor KN-93 reduces dopamine contents in PC12h cells. Biochemical and Biophysical Research Communications 181, 968–975.CrossRefGoogle Scholar
Turner, N. A., Walker, J. H., Ball, S. G. and Vaughan, P. F. ( 1996). Down-regulation or long-term inhibition of protein kinase C (PKC) reduces noradrenaline release evoked via either PKC-dependent or PKC-independent pathways in human SH-SY5Y neuroblastoma cells. Neuroscience Letters 220, 37–40.CrossRefGoogle Scholar
Vieira, M. C., De Carvalho, T. U. and De Souza, W. ( 1994). Effect of protein kinase inhibitors on the invasion process of macrophages by Trypanosoma cruzi. Biochemical and Biophysical Research Communications 203, 967–971.CrossRefGoogle Scholar
Ward, G. E., Fujioka, H., Aikawa, M. and Miller, L. H. ( 1994). Staurosporine inhibits invasion of erythrocytes by malarial merozoites. Experimental Parasitology 79, 480–487.CrossRefGoogle Scholar
Wiser, M. F. and Schweiger, H. G. ( 1985). Cytosolic protein kinase activity associated with the maturation of the malaria parasite Plasmodium berghei. Molecular and Biochemical Parasitology 17, 179–189.CrossRefGoogle Scholar