Artículo de revista
Glutathione transferase mu 2 protects glioblastoma cells against aminochrome toxicity by preventing autophagy and lysosome dysfunction
Fecha
2014Registro en:
Autophagy, Volumen 10, Issue 4, 2018, Pages 618-630
15548635
15548627
10.4161/auto.27720
Autor
Huenchuguala, Sandro
Muñoz, Patricia
Zavala, Patricio
Villa, Mónica
Urriola Cuevas, Carlos
Ahumada, Ulises
Graumann, Rebecca
Nore, Beston F.
Couve, Eduardo
Mannervik, Bengt
Paris Pizarro, Irmgard
Segura Aguilar, Juan
Institución
Resumen
U373MG cells constitutively express glutathione S-transferase mu 2 (GSTM2) and exhibit 3H-dopamine uptake, which is inhibited by 2 μM of nomifensine and 15 μM of estradiol. We generated a stable cell line (U373MGsiGST6) expressing an siRNA against GSTM2 that resulted in low GSTM2 expression (26% of wild-type U373MG cells). A significant increase in cell death was observed when U373MGsiGST6 cells were incubated with 50 μM purified aminochrome (18-fold increase) compared with wild-type cells. The incubation of U373MGsiGST6 cells with 75 μM aminochrome resulted in the formation of autophagic vacuoles containing undigested cellular components, as determined using transmission electron microscopy. A significant increase in autophagosomes was determined by measuring endogenous LC3-II, a significant decrease in cell death was observed in the presence of bafilomycin A1, and a significant increase in cell death was observed in the presence of trehalose. A significant increase in LAMP2 immunosta