INVESTIGADORES
GALIANO Mauricio Raul
congresos y reuniones científicas
Título:
Altered Stress Granules dynamic modulates cell fate in bortezomib-treated glioma cells
Autor/es:
LAURA V. BONNET; JÉSICA FLORES MARTÍN; MAURICIO R. GALIANO; MARTA E. HALLAK
Lugar:
Buenos Aires
Reunión:
Congreso; Reunión conjunta de Sociedades de Biociencias; 2017
Resumen:
Among different human glioma cells, we determined a differential susceptibilityto Bortezomib treatment (BT) that correlates with variable expression levels andsubcellular localization of arginylated calreticulin (R-CRT), together with ERstress induction. Those cells (MO59K) that are resistant to BT showed a smallvariation of R-CRT, which appears confined to increased stress granules (SGs)formation and sharp ER stress. Whereas those cells (HOG) that are susceptibleto BT showed intracellular increased levels and plasma membrane enrichmentof R-CRT, where it participates in a caspase 3 dependent pro-apoptoticsignaling, after strong ER stress induced by the drug. Co-treatment of HOGcells with BT and Tannic Acid (TA, Ate1 inhibitor) reverts the cytotoxicity shownby BT alone. Since the formation of SGs is associated with a greater resistanceto chemotherapy, we evaluate how its dynamism is affected in both HOG andMO59K. Firstly, by immunofluorescence, we determined that HOG exposed toboth BT and TA showed an increase of SGs formation in agreement withenhanced resistance of these cells to BT, change that is not shown by co-treated MO59K. However, the later showed the formation of smaller SGs afterco-treatment. Secondly, as autophagy is known to degrade SGs, we alsoevaluate whether it is induced in both cell types during BT. After BT treatmentMO59K showed a clear induction of LC3 II. By contrast, a strong activation ofautophagy was shown by HOG even in control condition (non-treated cells),what may correspond with a reduced number of SGs in these cells. Hence, theincreased susceptibility of HOG cells to BT is associated with a markedly activeautophagy and robust induction of ER stress, which strongly promotesarginylation of CRT and R-CRT exposure at plasma membrane. By contrast, inMO59K cells a controlled induction of both autophagy and ER stress maintainsreduced levels of R-CRT that mainly associates with SGs, as a hallmark of BTresistance.