Manganese Induces Mitochondrial Dynamics Impairment and Apoptotic Cell Death. A Study in Human Gli36 Cells

AGUSTINA ALAIMO; ROXANA GOROJOD; ESTEBAN MIGLIETTA; ALEJANDOR VILLAREAL; ALBERTO RAMOS; MÓNICA KOTLER

NEUROSCIENCE LETTERS

ELSEVIER IRELAND LTD

Año: 2013 vol. 554 p. 76 - 81

0304-3940

tManganese (Mn) is an essential trace element due to its participation in many physiological processes.However, overexposure to this metal leads to a neurological disorder known as Manganism whose clin-ical manifestations and molecular mechanisms resemble Parkinson?s disease. Several lines of evidenceimplicate astrocytes as an early target of Mn neurotoxicity being the mitochondria the most affectedorganelles. The aim of this study was to investigate the possible mitochondrial dynamics alterations inMn-exposed human astrocytes. Therefore, we employed Gli36 cells which express the astrocytic mark-ers GFAP and S100B. We demonstrated that Mn triggers the mitochondrial apoptotic pathway revealedby increased Bax/Bcl-2 ratio, by the loss of mitochondrial membrane potential and by caspase-9 acti-vation. This apoptotic program may be in turn responsible of caspase-3/7 activation, PARP-1 cleavage,chromatin condensation and fragmentation. In addition, we determined that Mn induces deregulationin mitochondria-shaping proteins (Opa-1, Mfn-2 and Drp-1) expression levels in parallel with the dis-ruption of the mitochondrial network toward to an exacerbated fragmentation. Since mitochondrialdynamics is altered in several neurodegenerative diseases, these proteins could become future targets tobe considered in Manganism treatment.