2 feb. 2012

Alberto Anel de CliNK en el Congreso "V International Conference BIFI 2012"
Muerte celular inducida por la granulisina en tumores hematológicos humanos

Sábado 4 de Febrero a las 12.10 h.

Alberto Anel, Catedrático e investigador senior dentro del Grupo "Apoptosis, Inmunidad y Cáncer"  "Granulysin-induced cell death of human hematological tumors" (Muerte celular inducida por la granulisina en tumores hematológicos humanos) en "The V International Conference of the Institute for Biocomputation and Physics of Complex Systems" (BIFI).

En esta charla se compartirán los conocimientos que hasta ahora han conseguido con la granulisina, proteína que poseen las células "NK" y que se está produciendo en el laboratorio del equipo de Alberto Anel. Se describirá el mecanimo por el cual esta proteína mata a células leucémicas in vitro. En breve se comenzará la experimentación animal para evaluar la posibilidad de utilizar esta proteína en el tratamiento del cáncer.

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Abstract

Alberto Anel, Adriana Aporta, Marta Pérez, Elena Catalán, Patricia Galán, Patricia Balsas, Javier Naval, Isabel Marzo & Julián Pardo

Granulysin-induced cell death in human hematological tumors
Granulysin is a human protein with no homolog in mice, that is contained in the granules of cytotoxic T lymphocytes (CTL) and natural killer (NK) cells, which most important function seems to be the direct lysis of intracellular bacteria such as M. tuberculosis . On the other hand, granulysin is also able to kill tumoral cells directly. We have studied the mechanism of granulysin-induced cell death using the human cell line Jurkat and its derivatives and also different human multiple myeloma cell lines. Granulsyin induces apoptotic cell death, characterized by phosphatidylserine exposure before membrane permeabilization and caspase-3 activation. Granulysin activates the mitochondrial apoptotic cell death pathway, and Jurkat cells that over-express anti-apoptotic memberas of the Bcl2 family, such as Jurkat-Bcl-2 and Jurkat-BclxL cells, or that lack the expression of the pro-apoptotic members of this family Bax and Bak, Jurkat-shBak cells, are significantly protected from granulysin-induced apoptosis. The mitochondrial apoptotic pathway is activated by intracellular calcium increase and subsequent production of mitochondrial reactive oxygen species (ROS) and granulysin-induced cell death is completely prevented by ROS scavengers such as MnTBAP or in Jurkat cells depleted of mitochondrial DNA, Jurkat-rº cells. The effect of granulysin on different human multiple myeloma cell lines was studied, observing a different degree of sensitiviyt depending on the cell line. Multiple myeloma sensitivity to granulysin correlated with the pattern of expression of pro- or anti-apoptotic members of the Bcl2 family, confirming mitochondrial implication in granulysin-induced apoptosis.

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