A caspase-independent pathway is involved in manganese-induced apoptosis in BV-2 microglial cells

PORTE ALCON S; GOROJOD RM; ALAIMO A; KOTLER ML

Ciudad Autonoma de Buenos Aires

Jornada; Jornadas Interdisciplinarias de Química Biológica; 2017

Departamento de Química Biológica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires

Manganese (Mn) overexposure causes a neurodegenerative disease known as Manganism. Several mechanisms have been implicated in Mn neurotoxicity including oxidative stress (OS) and inflammation. Microglia are activated in response to Mn and release various pro-inflammatory cytokines (IL-1β, IL-6 and TNF-α) and soluble factors, includingreactive oxygen and nitrogen species, which could promote neuronal death. However, little is known about Mn toxicity in microglia. We previously demonstrated that BV-2 microglial cells exposed to Mn (250 and750µM; 24h) exhibit apoptotic features such as the activation of caspases involved in intrinsic and extrinsic cell death pathways. In addition, we reported that OS and lisosomal membrane permeabilization were involved in cell death. In the present work we continue unraveling the molecular pathways involved in Mn-induced toxicity in BV-2 cells.To determine the role of caspases, we performed cell viability assays (MTT) in the presence ofcaspase-8(Ac-LEHD-CMK), caspase-9 (Z-IETD-FMK) and pan-caspase (Z-VAD-FMK) inhibitors. Interestingly, these inhibitors did not prevent Mn-induced cell death. In accordance, Mn increased a 68% (p