Myocardial cellular damage and the activity of the mitochondrial ATP synthase in rats infected with a Colombian strain of Trypanosoma cruzi
Keywords:
Trypanosoma cruzi, Chagas disease, Chagas cardiomyopathy, energy metabolism, mitochondria
Abstract
Introduction. Chagas disease is the main cause of cardiomyopathy in endemic regions of Latin America. Alterations in the cardiac mitochondrial energy metabolism caused by Trypanosoma cruzi can be involved in the development of this cardiomyopathy during the course of Chagas disease.Objective. The cellular injury of the rat myocardium was investigated in rats infected with the Colombian Mg8 strain of Trypanosoma cruzi. The activity of mitochondrial ATP synthase was measured to determine the relationship heart damage with the energy metabolism.
Materials and methods. Two groups of five rats each were infected with tripomastigotes, with 1 group of 6 rats serving as controls. The course of infection was characterized by parasitological, histopathological and molecular studies. The mitochondrial ATP synthase activity of the myocardium was evaluated in all rats.
Results. Peak parasitaemia (day 26 post infection) and the time of parasite clearance from circulating blood (day 60 post infection) were determined for acute and chronic phase models. The histopathological and molecular results showed that the Colombian Mg8 strain has tropism to the cardiac tissue and causes considerable cellular injury of the myocardium in rats during both phases. Despite the lesions observed in infected rats, no statistical difference in the activity of the mitochondrial ATPsynthase was observed between them and the non-infected rats.
Conclusion. Mitochondrial energy metabolism of the cardiomyocites does not appear to change during cellular injury of rat myocardium associated with infection by the Colombian Mg8 T. cruzi strain.
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References
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2. Uyemura SA, Jordani MC, Polizello AC, Curti C. Heart FoF1-ATPase changes during the acute phase of Trypanosoma cruzi infection in rats. Mol Cell Biochem 1996;165:127-33.
3. Vyatkina G, Bhatia V, Gerstner A, Papaconstantinou J, Garg N. Impaired mitochondrial respiratory chain and bioenergetics during chagasic cardiomyopathy development. Biochim Biophys Acta 2004;1689:162-73.
4. Harris DA, Das AM. Control of mitochondrial ATP synthesis in the heart. Biochem J 1991;280:561-73.
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12. Camargo EP. Growth and differentiation in Trypanosoma cruzi. Origin of metacyclic trypanosomes in liquid media. Rev Inst Med Trop Sao Paulo 1964;12:93-100.
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26. Jones EM, Colley DG, Tostes S, Lopes ER, Vnencak-Jones CL, McCurley TL. Amplification of a Trypanosoma cruzi DNA sequence from inflammatory lesions in human chagasic cardiomyopathy. Am J Trop
Med Hyg 1993;48:348-57.
27. Köberle F. Chagas´ disease and Chagas´ syndroms: the pathology of American trypanosomiasis. Adv Parasitol 1968;6:63-116.
28. Teixeira AR. Patogenia da doenVa de Chagas. J Bras Med 1980;38:23-33.
29. Oliveira JS. A natural human model for intrinsic heart nervous system denervation: Chagas´ cardiopathy. Am Heart J 1985;110:1092-8.
30. Junqueira Junior LF, Beraldo PS, Chapadeiro E, Jesus PC. Cardiac autonomic dysfunction and neuroganglionitis in a rat model of chronic Chagas´ disease. Cardiovasc Res 1992;26:324-9.
31. Rossi MA, Carobrez SG. Experimental Trypanosoma cruzi cardiomyopathy in BALB/c mice histochemical evidence of hypoxic changes in the myocardium. Br J Exp Pathol 1985;66:155-60.
32. Rossi MA. Microvascular changes as a cause of chronic cardiomyopathy in Chagas´s disease. Am Heart J 1990;20:233-6.
33. Nohl H, Gille L, Stanick K. Intracellular generation of reactive oxygen species by mitochondria. Biochem Pharmacol 2005;69:719-23.
34. Veksler VI, Kuznetsov AV, Sharov VG, Kapelko VI, Saks VA. Mitochondrial respiratory parameters in cardiac tissue: a novel method of assessment by using saponin-skinned fibers. Biochim Biophys Acta 1987;892:191-6.
35. Rendon DA, Lopez LF. Mitochondrial oligomycinsensitive ATPase during isoproterenol-induced cell injury of myocardium. Arch Inst Cardiol Mex 2000;70:130-5.
36. Rendon DA, Lopez LF. Activation of mitochondrial oxidative phosphorylation during (+/-)-isoproterenolinduced cell injury of myocardium. Arch Cardiol Mex 2001;71:13-9.
37. Denicola Seoane A, Rubbo H, Prodanov E, Turrens J. Succinate-dependent metabolism in Trypanosoma cruzi epimastigotes. Mol Biochem Parasitol 1992;54: 43-50.
2. Uyemura SA, Jordani MC, Polizello AC, Curti C. Heart FoF1-ATPase changes during the acute phase of Trypanosoma cruzi infection in rats. Mol Cell Biochem 1996;165:127-33.
3. Vyatkina G, Bhatia V, Gerstner A, Papaconstantinou J, Garg N. Impaired mitochondrial respiratory chain and bioenergetics during chagasic cardiomyopathy development. Biochim Biophys Acta 2004;1689:162-73.
4. Harris DA, Das AM. Control of mitochondrial ATP synthesis in the heart. Biochem J 1991;280:561-73.
5. Garg N, Popov VL, Papaconstantinou J. Profiling gene transcription reveals a deficiency of mitochondrial oxidative phosphorylation in Trypanosoma cruzi infected murine hearts: implications in chagasic myocarditis development. Biochim Biophys Acta 2003;1638:106-20.
6. Jennings RB, Hawkins HK, Lowe JE, Hill ML, Klotman S, Reimer KA. Relation between high energy phosphate and lethal injury in myocardial ischemia in the dog. Am J Pathol 1978;92:187-214.
7. Boyer PD. The ATP synthase a splendid molecular machine. Annu Rev Biochem 1997;66:717-49.
8. Das Anibh M. Regulation of mitochondrial ATP synthase activity in human myocardium. Clin Sci 1998;94:499-504
9. Das Anibh M. Regulation of the mitochondrial ATPsynthase activity in health and disease. Mol Genet Metab 2003;79:71-82.
10. Senior AE, Nadanaciva S, Weber J. The molecular mechanism of ATP synthesis by Fo F1-ATP synthase. Biochim Biophys Acta 2002;1553:188-211.
11. Mejía AM, Triana O. Análisis por LSSP-PCR de la variabilidad genética de Trypanosoma cruzi en sangre y órganos de ratones. Biomédica 2005;25:76-86.
12. Camargo EP. Growth and differentiation in Trypanosoma cruzi. Origin of metacyclic trypanosomes in liquid media. Rev Inst Med Trop Sao Paulo 1964;12:93-100.
13. Brener Z. Therapeutic activity and criterion of cure on mice experimentally infected with Trypanosoma cruzi. Rev Inst Med Trop Sao Paulo 1962;4:389-96.
14. Miller SA, Dykes DD, Polesky HF. A simple salting out procedure for extracting DNA from human nucleated cells. Nucleic Acids Res 1988;16:1215.
15. Sambrook J, Fritsch EF, Maniatis T. Molecular cloning. A laboratory manual. 2 ed. Cold Spring Harbor, New York: Cold Harbor Laboratory Press;1989.
16. Maniatis T, Fritsch EF, Sambrook J. Molecular cloning. A laboratory manual. Cold Spring Harbor, New York: Cold Harbor Laboratory Press;1982.
17. Sturm N, Degrave W, Morel C, Simpson L. Sensitive detection and schizodeme classification of Trypanosoma cruzi cells by amplification of kinetoplast minicircle DNA sequences. Use in diagnosis of Chagas disease. Mol Biochem Parasitol 1989;33:205-14.
18. Fernández O, Souto RP, Castro JA, Pereira JB, Fernández NC, Junqueira AC, et al. Brazilian isolates of Trypanosoma cruzi from humans and triatomines classified into two lineages using mini-exon and ribosomal RNA sequences. Am J Trop Med Hyg 1998;58:807-11.
19. Nishimura M, Ito T, Change B. Studies on bacterial photophosphorylation. III. A sensitive and rapid method of determination of photophosphorylation. Biochim Biophys Acta 1962;59:177-82.
20. Gornall AG, Bardawill CJ, David MM. Determination of serum proteins by means of the biuret reaction. J Biol Chem 1949;177:751-66.
21. Chagas C. Estado sobre a morfologia e o ciclo evolutivo do Schizotrypanum cruzi, n. gen. sp. agente etiológico de nova entidade mórbida do homen. Mem Inst Oswaldo Cruz 1909;1:159-219.
22. Mukherjee S, Belbin TJ, Spray DC, Iacobas Da, Weiss LM, Kitsis RN, et al. Microarray analysis of changes in gene expression in a murine model of chronic chagasic cardiomyopathy. Parasitol Res
2003;91:187-96.
23. Moreira da Silva A, Ramirez Le, Vargas M, Chapadeiro E, Brener Z. Evaluation of the rabbit as a model for Chagas disease - II. Histopatologic studies of the Herat, digestive tract and skeletal muscle. Mem Inst Oswaldo Cruz 1996;91:199-206.
24. de Oliveira JS, Bestetti RB, Soares EG, Marin Nieto JA. Ajmaline-induced electrocardiographic changes in chronic Trypanosoma cruzi-infected rats. Trans R Soc Trop Med Hyg 1986;80:415-9.
25. Acosta AM, Santos-Buch CA. Autoimmune myocarditis induced by Trypanosoma cruzi. Circulation 1985;71:1255-61.
26. Jones EM, Colley DG, Tostes S, Lopes ER, Vnencak-Jones CL, McCurley TL. Amplification of a Trypanosoma cruzi DNA sequence from inflammatory lesions in human chagasic cardiomyopathy. Am J Trop
Med Hyg 1993;48:348-57.
27. Köberle F. Chagas´ disease and Chagas´ syndroms: the pathology of American trypanosomiasis. Adv Parasitol 1968;6:63-116.
28. Teixeira AR. Patogenia da doenVa de Chagas. J Bras Med 1980;38:23-33.
29. Oliveira JS. A natural human model for intrinsic heart nervous system denervation: Chagas´ cardiopathy. Am Heart J 1985;110:1092-8.
30. Junqueira Junior LF, Beraldo PS, Chapadeiro E, Jesus PC. Cardiac autonomic dysfunction and neuroganglionitis in a rat model of chronic Chagas´ disease. Cardiovasc Res 1992;26:324-9.
31. Rossi MA, Carobrez SG. Experimental Trypanosoma cruzi cardiomyopathy in BALB/c mice histochemical evidence of hypoxic changes in the myocardium. Br J Exp Pathol 1985;66:155-60.
32. Rossi MA. Microvascular changes as a cause of chronic cardiomyopathy in Chagas´s disease. Am Heart J 1990;20:233-6.
33. Nohl H, Gille L, Stanick K. Intracellular generation of reactive oxygen species by mitochondria. Biochem Pharmacol 2005;69:719-23.
34. Veksler VI, Kuznetsov AV, Sharov VG, Kapelko VI, Saks VA. Mitochondrial respiratory parameters in cardiac tissue: a novel method of assessment by using saponin-skinned fibers. Biochim Biophys Acta 1987;892:191-6.
35. Rendon DA, Lopez LF. Mitochondrial oligomycinsensitive ATPase during isoproterenol-induced cell injury of myocardium. Arch Inst Cardiol Mex 2000;70:130-5.
36. Rendon DA, Lopez LF. Activation of mitochondrial oxidative phosphorylation during (+/-)-isoproterenolinduced cell injury of myocardium. Arch Cardiol Mex 2001;71:13-9.
37. Denicola Seoane A, Rubbo H, Prodanov E, Turrens J. Succinate-dependent metabolism in Trypanosoma cruzi epimastigotes. Mol Biochem Parasitol 1992;54: 43-50.
How to Cite
1.
Rendón DA, Genes CM, Triana O. Myocardial cellular damage and the activity of the mitochondrial ATP synthase in rats infected with a Colombian strain of Trypanosoma cruzi. Biomed. [Internet]. 2007 Jan. 1 [cited 2025 Apr. 5];27(1esp):40-9. Available from: https://revistabiomedicaorg.biteca.online/index.php/biomedica/article/view/247
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