INVESTIGADORES
REPETTO Marisa Gabriela
congresos y reuniones científicas
Título:
Copper-induced cell death and the protective role of glutathione: the implication of impaired protein folding rather than oxidative stress
Autor/es:
SAPORITO MAGRIÑÁ, CHRISTIAN; LAIRIÓN, FABIANA; REPETTO, MARISA GABRIELA
Lugar:
Mar del Plata
Reunión:
Congreso; LXIII Reunión anual de la Sociedad Argentina de Investigación Clínica; 2018
Institución organizadora:
Sociedad Argentina de Investigación Clínica
Resumen:
Copper (Cu) overload is toxic for cells as observed in Wilson?s disease.However, the events driving cell death due to Cu ions have not been yet elucidated. Whereas the intracellular accumulation of this metal has been reported to promote oxidative damage to biomolecules, antioxidant therapies have not been reported to be effective in the treatment of Cu imbalance-related disorders. Through gene set enrichment analysis (GSEA) we analyzed the biological processes which are activated or deactivated in the RNA microarraydata collected from BEAS-2B and HCT116 cells exposed to 800 μM and 1400 μM Cu(II), respectively. Such concentrations result in nearly 50% cell death after 24 hours. Our gene expression kinetic indicates a strong heat shock response (HSR) and unfolded protein response (UPR) activation along with a slight intrinsic apoptosis signaling in response to the UPR. Notably, no activation of antioxidant response is observed. Cu overload leads to a strong deactivation ofall processes related to the progression of the cell cycle, transcription,cytosolic translation, mitochondrial translation and mitochondrial respiration. In conclusion, Cu overload impairs proteostasis but the absence of a consistent antioxidant response suggests that the metal may promote protein misfolding independently of its pro-oxidant features. Interestingly, the strong deactivation of cell cycle progression, protein synthesis and mitochondrial respiration-related processes indicates that Cu-induced cell death may involve signaling pathways which may be exploited to develop new therapeuticapproaches for Cu disorders.