Autophagy protects BV-2 microglial cells from manganese-induced cell death

PORTE ALCON, SOLEDAD; PORTE ALCON, SOLEDAD; GOROJOD, ROXANA MAYRA; GOROJOD, ROXANA MAYRA; KOTLER, MÓNICA LIDIA; KOTLER, MÓNICA LIDIA

Creta

Workshop; EMBO workshop "Cell Death in Immunity and Inflammation"; 2019

EMBO

Chronic overexposure to manganese (Mn) causes a parkinsonian-like syndromeknown as Manganism. Besides neurons, glial cells are susceptible to Mn-induceddamage. We have demonstrated that Mn triggers microglial cell death mediated byregulated necrosis, particularly parthanatos and lysosomal disruption. Autophagy is a catabolic pathway in which cellular components are degraded by lysosomes inresponse to stress conditions, thus allowing cells to adapt to the environment.Nevertheless, autophagy activation may result in both beneficial or detrimental effects, depending on the context. Evidence indicates that Mn activates autophagy in microglial cells. However, the role of autophagy in Mn-induced microglial cell death remains unknown. To address this question, we exposed BV-2 cells to Mn and analyzed the autophagic activation over time and its role in the cellular fate. First, we found a time-dependent increase of LC3-II protein levels (WB and ICC). The expression of the autophagic substrate protein p62 followed the same kinetics as LC3-II, suggesting that autophagy is impaired. Nevertheless, both LC3-II and p62 expression levels increased even more in the presence of Bafilomycin A1. This observation is compatible with an, at least in part, active autophagic flux. Induction of autophagy by Rapamycin partially prevented Mn toxicity at 24 h (MTT). Accordingly, its inhibition (3-MA) caused a higher loss of cell viability than Mn alone at 12 h. Our results suggest that autophagy plays a protective role in Mn-induced cell death representing a valuable contribution to be considered in future research concerning Manganism therapies.