Mechanisms of Induction of Apoptosis in Hematopoietic cells by Sulphated Bacterial Exopolysaccharides

  1. GIRISH K., SRIVASTAVA
Supervised by:
  1. Ignacio Jesús Molina Pineda de las Infantas Director
  2. María del Carmen Ruiz Ruiz Co-director

Defence university: Universidad de Granada

Fecha de defensa: 13 March 2008

Committee:
  1. Emilia Quesada Arroquia Chair
  2. Ana Clara Abadía Molina Secretary
  3. Javier Martín Ibáñez Committee member
  4. Enrique García Olivares Committee member
  5. Francisco Martín Molina Committee member

Type: Thesis

Abstract

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 EPS 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 inmunological importance of EPS of halophilic bacterial H. maura and H. anticariensis. The results 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 EPS N12 or EPS FP34 from H. anticariensis. The proapoptotic effect of the oversulphated form of EPS B100 shows a gradient of sensitivity within a panel of 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 orderlyactivation of caspases, the alteration of mitochondrial membrane potential and the production of ROS are evidence supporting that apoptosis induced by the oversulphated B100 EPS is triggered mainly through mithocondrial or intrinsic pathway of apoptosis. The potent proapoptopic effect of peripheral cells from a patient with T-all opens the possibility for thrapeutic applications of the oversulphated B100 EPS in human T cell leukemias.