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From the cell biology to the development of new chemotherapeutic approaches against trypanosomatids: dreams and reality.

De Souza W - Kinetoplastid Biol Dis (2002)

Bottom Line: These organisms are also of biological interest since they are able to change the morphology according to the environment where they live, through a process of reversible cell transformation, and possess structures and organelles that are not found in mammalian cells.In addition, the present knowledge of structures and organelles such as the nucleus, the plasma membrane, the sub-pellicular microtubules, the flagellum, the kinetoplast-mitochondrion complex, the peroxisome (glycosome), the acidocalcisome and the structures and organelles involved in the endocytic pathway, is reviewed from a cell biology perspective.The possible use of available data for the development of new anti parasite drugs is also discussed.

View Article: PubMed Central - HTML - PubMed

Affiliation: Laboratório de Ultraestrutura Celular Hertha Meyer, Instituto de Biofisica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, CCSBloco G, 21941900, Rio de JaneiroRJ, Brasil. wsouza@biof.ufrj.br

ABSTRACT
Members of the Trypanosomatidae family comprise a large number of species that are causative agents of important diseases such as sleeping sickness, Chagas' disease and Leishmaniasis. These organisms are also of biological interest since they are able to change the morphology according to the environment where they live, through a process of reversible cell transformation, and possess structures and organelles that are not found in mammalian cells. This review analyses the process of transformation, which takes place during the life cycle of Trypanosoma cruzi in the vertebrate and invertebrate hosts. Special attention is given to the interaction of the parasite with vertebrate cells. In addition, the present knowledge of structures and organelles such as the nucleus, the plasma membrane, the sub-pellicular microtubules, the flagellum, the kinetoplast-mitochondrion complex, the peroxisome (glycosome), the acidocalcisome and the structures and organelles involved in the endocytic pathway, is reviewed from a cell biology perspective. The possible use of available data for the development of new anti parasite drugs is also discussed.

No MeSH data available.


Related in: MedlinePlus

General view of an epimastigote form of T. cruzi incubated in the presence of a drug which inhibits the biosynthesis of ergosterol. An intense swelling of the mitochondrion is observed.
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Figure 16: General view of an epimastigote form of T. cruzi incubated in the presence of a drug which inhibits the biosynthesis of ergosterol. An intense swelling of the mitochondrion is observed.

Mentions: Taken together all information presently available on the mitochondrion-kinetoplast complex of trypanosomatids we can conclude that it offers several potential targets for the action of chemotherapeutic agents. First, we must not forget that this complex structure is a mitochondrion whose functionality is vital for the survival of the cell. It has been shown recently that in contrast to the mitochondria of mammalian cells, the mitochondrial membrane of trypanosomatids possess a significant amount of sterols. This fact probably explains the dramatic effect observed in the mitochondria of cells incubated in the presence of drugs which inhibit the biosynthesis or ergosterol (Fig. 16), and which have been shown to be among the most interesting prospects for the chemotherapy of Chagas'disease and leishmaniasis (Review in [66]). Drugs which interfere with one of the several steps of the processes of minicircle and maxicircle replication, inhibitors of topoisomerases, DNA polymerases, RNA-editing, etc, should be analyzed in more detail in the next years.


From the cell biology to the development of new chemotherapeutic approaches against trypanosomatids: dreams and reality.

De Souza W - Kinetoplastid Biol Dis (2002)

General view of an epimastigote form of T. cruzi incubated in the presence of a drug which inhibits the biosynthesis of ergosterol. An intense swelling of the mitochondrion is observed.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC119324&req=5

Figure 16: General view of an epimastigote form of T. cruzi incubated in the presence of a drug which inhibits the biosynthesis of ergosterol. An intense swelling of the mitochondrion is observed.
Mentions: Taken together all information presently available on the mitochondrion-kinetoplast complex of trypanosomatids we can conclude that it offers several potential targets for the action of chemotherapeutic agents. First, we must not forget that this complex structure is a mitochondrion whose functionality is vital for the survival of the cell. It has been shown recently that in contrast to the mitochondria of mammalian cells, the mitochondrial membrane of trypanosomatids possess a significant amount of sterols. This fact probably explains the dramatic effect observed in the mitochondria of cells incubated in the presence of drugs which inhibit the biosynthesis or ergosterol (Fig. 16), and which have been shown to be among the most interesting prospects for the chemotherapy of Chagas'disease and leishmaniasis (Review in [66]). Drugs which interfere with one of the several steps of the processes of minicircle and maxicircle replication, inhibitors of topoisomerases, DNA polymerases, RNA-editing, etc, should be analyzed in more detail in the next years.

Bottom Line: These organisms are also of biological interest since they are able to change the morphology according to the environment where they live, through a process of reversible cell transformation, and possess structures and organelles that are not found in mammalian cells.In addition, the present knowledge of structures and organelles such as the nucleus, the plasma membrane, the sub-pellicular microtubules, the flagellum, the kinetoplast-mitochondrion complex, the peroxisome (glycosome), the acidocalcisome and the structures and organelles involved in the endocytic pathway, is reviewed from a cell biology perspective.The possible use of available data for the development of new anti parasite drugs is also discussed.

View Article: PubMed Central - HTML - PubMed

Affiliation: Laboratório de Ultraestrutura Celular Hertha Meyer, Instituto de Biofisica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, CCSBloco G, 21941900, Rio de JaneiroRJ, Brasil. wsouza@biof.ufrj.br

ABSTRACT
Members of the Trypanosomatidae family comprise a large number of species that are causative agents of important diseases such as sleeping sickness, Chagas' disease and Leishmaniasis. These organisms are also of biological interest since they are able to change the morphology according to the environment where they live, through a process of reversible cell transformation, and possess structures and organelles that are not found in mammalian cells. This review analyses the process of transformation, which takes place during the life cycle of Trypanosoma cruzi in the vertebrate and invertebrate hosts. Special attention is given to the interaction of the parasite with vertebrate cells. In addition, the present knowledge of structures and organelles such as the nucleus, the plasma membrane, the sub-pellicular microtubules, the flagellum, the kinetoplast-mitochondrion complex, the peroxisome (glycosome), the acidocalcisome and the structures and organelles involved in the endocytic pathway, is reviewed from a cell biology perspective. The possible use of available data for the development of new anti parasite drugs is also discussed.

No MeSH data available.


Related in: MedlinePlus