CIBICI   14215
CENTRO DE INVESTIGACION EN BIOQUIMICA CLINICA E INMUNOLOGIA
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
Hyperglicemia-linked metabolites disrupts mitochondrial dynamics and physiology in the central nervous system
Autor/es:
VIVIANE GLASER; PERTILE REMOR; FILIPE JOSÉ DE MATOS; LILIANA DEL VALLE SOSA; JESICA FLORES-MARTIN,; SUSANA GENTI-RAIMONDI,; ALICIA TORRES; SILVIA OLIVERA-BRAVO; RODRIGO BAINY LEAL, ; ANA LUCIA DE PAUL, ; ALEXANDRA LATINI
Lugar:
Lisboa
Reunión:
Congreso; 18th European Bioenergetics Conference EBEC; 2014
Resumen:
Chronic hyperglycemia, characteristic of diabetes mellitus (DM), appears to activate pathways implicated in the pathogenesis of DM complications, including methylglyoxal (MG) and advanced glycation end products (AGEs) formation. However, the impact of these compounds on the central nervous system (CNS) is virtually unknown. Here, it was investigated the effect of chronic hyperglycemia, MG and AGEs, on mitochondrial physiology and dynamics in the CNS. Chronic hyperglycemia was induced in Wistar rats by injecting a single dose of streptozotocin (STZ, 55mg/kg, i.p.). Animals with glycemia >200mg/dL were considered hyperglycemic and were maintained in this condition for 60 days. Control animals received injection of vehicle instead of STZ. It was observed that chronic hyperglycemia changed mitochondrial dynamics or biogenesis in olfactory bulb preparations by increasing the number of mitochondria. In order to better understand the effect of the accumulating metabolites under this hyperglycemic state, we analyzed the individual effect of MG and AGEs on mitochondria dynamic or physiology in cultures astrocytes. AGEs treatment induced mitochondrial reorganization, by reducing the size and increasing the number of this organelle in C6 astroglioma cells. In addition the other hyperglycemic-linked metabolite, MG, provoked increased oxygen consumption (basal respiration and respiring state IV) and reduced mitochondrial respiratory control, indicating MG-induced uncoupling of mitochondria. In agreement, AGEs provoked reduced mitochondrial membrane potential on rat primary cortical astrocytes cell culture, suggesting that altered mitochondrial dynamics is directly related to the MG uncoupling properties. Furthermore, the increased content of uncoupled mitochondria did not stimulate autophagy, indicating that dysfunctional reactive oxygen species-producing organelles are being accumulated in astrocytes. In conclusion, chronic hyperglycemia and hyperglycemia-linked metabolites (MG and AGEs) disrupts mitochondrial dynamics and physiology in nerve cells. The phenomenon might induce cell death, and therefore, a higher predisposition for neurodegenerative disorders development in individuals affected by DM.