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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

Two different views of the interaction of T. cruzi with macrophages, as seen by scanning electron microscopy.
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Figure 5: Two different views of the interaction of T. cruzi with macrophages, as seen by scanning electron microscopy.

Mentions: The initial process of T. cruzi host cell interaction involves attachment of the parasite to the host cell surface (Figs. 4,5). Videomicroscopic observation of the interaction shows that not all parasites that touch the host cell surface remain attached. Attachment is usually more evident in situations in which the subsequent phase of internalization is interrupted, as occurs in cells previously treated with drugs which interfere with actin filaments [12]. The available data indicate that attachment is due to a process of cell-to-cell recognition with the involvement of sugar residues exposed on the surface of both interacting cells [13]. There is a large body of evidence showing that sialic acid residues are involved in the recognition process [14]. One surface glycoprotein which possesses both neuraminidase and trans-sialidase activity plays a major role in T. cruzi host cell interaction [15]. This molecule belongs to a multigenic family coding for a group of heterogeneous proteins with molecular weights varying from 100 to 200 kDa. These proteins can be found in all developmental forms, however, they are more abundant in trypomastigote forms where they can be found on the parasite surface, attached to the plasma membrane via a GPI anchor sensitive to phospholipase C. Usually these proteins are found only in about 20% of the trypomastigote population and those expressing them correspond to the most invasive forms [16]. These molecules remove sialic acid residues, preferentially linked in a α-2,3 position, transferring it to acceptor molecules, mainly represented by a highly glycosylated protein of 70-200 kDa, known as Ssp3 [17], and of 3550 kDa molecule found in metacyclic trypomastigotes [18]. The trans-sialidase family also includes other glycoproteins which do not possess enzyme activity, but which are also involved on the process of T. cruzi host cell interaction, as is the case of one glycoprotein of 85 kDa known as Tc85 [19]. It has been shown that this molecule possesses adhesive properties to laminin and a carboxyl terminal segment that binds to cytokeratin 18 [20].


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

De Souza W - Kinetoplastid Biol Dis (2002)

Two different views of the interaction of T. cruzi with macrophages, as seen by scanning electron microscopy.
© Copyright Policy
Related In: Results  -  Collection

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

Figure 5: Two different views of the interaction of T. cruzi with macrophages, as seen by scanning electron microscopy.
Mentions: The initial process of T. cruzi host cell interaction involves attachment of the parasite to the host cell surface (Figs. 4,5). Videomicroscopic observation of the interaction shows that not all parasites that touch the host cell surface remain attached. Attachment is usually more evident in situations in which the subsequent phase of internalization is interrupted, as occurs in cells previously treated with drugs which interfere with actin filaments [12]. The available data indicate that attachment is due to a process of cell-to-cell recognition with the involvement of sugar residues exposed on the surface of both interacting cells [13]. There is a large body of evidence showing that sialic acid residues are involved in the recognition process [14]. One surface glycoprotein which possesses both neuraminidase and trans-sialidase activity plays a major role in T. cruzi host cell interaction [15]. This molecule belongs to a multigenic family coding for a group of heterogeneous proteins with molecular weights varying from 100 to 200 kDa. These proteins can be found in all developmental forms, however, they are more abundant in trypomastigote forms where they can be found on the parasite surface, attached to the plasma membrane via a GPI anchor sensitive to phospholipase C. Usually these proteins are found only in about 20% of the trypomastigote population and those expressing them correspond to the most invasive forms [16]. These molecules remove sialic acid residues, preferentially linked in a α-2,3 position, transferring it to acceptor molecules, mainly represented by a highly glycosylated protein of 70-200 kDa, known as Ssp3 [17], and of 3550 kDa molecule found in metacyclic trypomastigotes [18]. The trans-sialidase family also includes other glycoproteins which do not possess enzyme activity, but which are also involved on the process of T. cruzi host cell interaction, as is the case of one glycoprotein of 85 kDa known as Tc85 [19]. It has been shown that this molecule possesses adhesive properties to laminin and a carboxyl terminal segment that binds to cytokeratin 18 [20].

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