Tesis doctoral de Grosh K. Srivaslava
The biological importance of bacterial eps has been extensively reviewed in scientific documents, being evident that these peculiar molecules have an extraordinary potential for the development of new applications both in biotechnology and drug development. Some sulphated aps modulate the proliferation of different cell lines, and the presence of sulphated groups in eps may critically influence the biological activity of the molecule. Consistent with this observation, preliminary studies carried out in out in our group have shown that hyperoversulphated forms of eps of h. Maura (b100 and n12) and eps of h. Anticariensis (fp34) cause a profound inhibition of cell proliferation in certain haematopoietic tumor cell lines. In this work we have investigated the immunological important of eps of halophytic bacterial h. Maura and h. Anticariensis. The resultants showed that the oversulphated but not the native, form of h. Maura eps b100 is a potent inducer of apoptosis. This proapoptotic activity is not observed with any of the native or oversulphated forms of h. Maura aps n12 or eps fp34 form h. Anticarensis. The proapoptotic effect of the oversulphated form of eps b100 shows a gradient of sensitivity within a panel of hematopoietic and non-hematopoietic cells, being leukemic t cell lines the best target for the eps. Primary and non-tumor t lymphocytes are resistant to induction of apoptosis by oversulphated b100. The apoptosis induced by the oversulphated form of b100 involved an early activation of the caspase cascade. This apical caspase in this cascade is caspase-9. The orderly activation of caspases, the alteration of mitochondrial memebrane potential and the production of ros are evidence supporting that apoptosis induced by the oversulphated b100 eps is triggered mainly through the mitochondrial or intrinsic pathway of apoptosis. The potent proapoptotic effect of oversulpjated b100 on leukemic t cell lines as well as the effect observed on peripheral cells from a patient with t-all opens the possibility for therapeutic applications of the oversulphated b100 eps in human t cell leukemias.
Datos académicos de la tesis doctoral «Mechanism of induction of apoptosis in hematopoietic cells by sulphated bacterial exopolysaccharides«
- Título de la tesis: Mechanism of induction of apoptosis in hematopoietic cells by sulphated bacterial exopolysaccharides
- Autor: Grosh K. Srivaslava
- Universidad: Granada
- Fecha de lectura de la tesis: 13/03/2008
Dirección y tribunal
- Director de la tesis
- Ignacio Molina Pineda De Las Infantas
- Tribunal
- Presidente del tribunal: emilia Quesada
- Javier Martin ibañez (vocal)
- enrique Garcia olivares (vocal)
- Francisco Martin molina (vocal)