IMBECU   20882
INSTITUTO DE MEDICINA Y BIOLOGIA EXPERIMENTAL DE CUYO
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
Effects of temozolomide (TMZ) on the expression and interaccion of heat shock proteins (HSPS) and DNA repair proteins in human malignant glioma cells
Autor/es:
CASTRO G. N.; CAYADO-GUTIÉRREZ N.; ZOPPINO F. C. M.; FANELLI M. A.; CUELLO CARRION F. D.; SOTTILE, M. L.; NADIN S. B.; CIOCCA D. R.
Lugar:
Montevideo
Reunión:
Workshop; First Conference of the South American Chapter of Cell Stress Society International; 2014
Institución organizadora:
Cell Stress Society International
Resumen:
We previously reported that HSPs and other molecular markers were associated with high-grade astrocytomas suggesting that these markers are related with the disease outcome and the response to treatments. With the aim to better understand of resistance/susceptibility processes associated to TMZ treatment, we have studied the biological effects of TMZ administration in human glioma cell lines evaluating the expression of proteins related to treatment resistance and DNA repair. Three human glioma cell lines: Gli36, U87 and DBTRG were treated with TMZ. The effects of TMZ were evaluated by: cell viability and survival, apoptosis, senescence and comet assay. The expression of HSPA, HSPB1, MGMT, MLH1 and MSH2 was determined by immunocytochemistry, immunofluorescence and western blot. Immunoprecipitation was used to analyze protein interaction. The cell lines exhibited different viability, apoptosis and senescence after TMZ administration. Gli36 cells showed very low recovery capacity following TMZ administration and this was related to high DNA damage levels, however, the cells maintained their viability. In these cells MGMT, MSH2, HSPA and HSPB1 levels increased significantly after TMZ administration. MSH2 and HSPB1 proteins appeared colocalized in Gli36 cells by confocal microscopy. This colocalization increased after TMZ treatment. In immunoprecipitation analysis MSH2 and HSPB1 appeared interacting. In contrast, HSPB1 did not interact with MGMT. Conclusion: In this report we show biological effects of TMZ and the interaction between HSPB1 and MSH2 in glioma cells as a first step to better understand the mechanisms of TMZ sensitivity and to design novel therapies in neurooncology.