title: Beyond the redox imbalance: Oxidative stress contributes to an impaired GLUT3 modulation in Huntington's disease.
abstract: Failure in energy metabolism and oxidative damage are associated with Huntington's disease (HD). Ascorbic acid released during synaptic activity inhibits use of neuronal glucose, favouring lactate uptake to sustain brain activity. Here, we observe a decreased expression of GLUT3 in STHdhQ111 cells (HD cells) and R6/2 mice (HD mice). Localisation of GLUT3 is decreased at the plasma membrane in HD cells affecting the modulation of glucose uptake by ascorbic acid. An ascorbic acid analogue without antioxidant activity is able to inhibit glucose uptake in HD cells. The impaired modulation of glucose uptake by ascorbic acid is directly related to ROS levels indicating that oxidative stress sequesters the ability of ascorbic acid to modulate glucose utilisation. Therefore, in HD, a decrease in GLUT3 localisation at the plasma membrane would contribute to an altered neuronal glucose uptake during resting periods while redox imbalance should contribute to metabolic failure during synaptic activity.
authors.affiliation: Instituto de Bioquímica y Microbiología, Facultad de Ciencias, Universidad Austral de Chile, Valdivia, Chile; Center for Interdisciplinary Studies on the Nervous system (CISNe), Universidad Austral de Chile, Valdivia, Chile.
authors.forename: Adriana
authors.initials: A
authors.lastname: Covarrubias-Pinto
authors.affiliation: Instituto de Bioquímica y Microbiología, Facultad de Ciencias, Universidad Austral de Chile, Valdivia, Chile; Center for Interdisciplinary Studies on the Nervous system (CISNe), Universidad Austral de Chile, Valdivia, Chile.
authors.forename: Pablo
authors.initials: P
authors.lastname: Moll
authors.affiliation: Instituto de Bioquímica y Microbiología, Facultad de Ciencias, Universidad Austral de Chile, Valdivia, Chile; Center for Interdisciplinary Studies on the Nervous system (CISNe), Universidad Austral de Chile, Valdivia, Chile.
authors.forename: Macarena
authors.initials: M
authors.lastname: Solís-Maldonado
authors.affiliation: Instituto de Bioquímica y Microbiología, Facultad de Ciencias, Universidad Austral de Chile, Valdivia, Chile; Center for Interdisciplinary Studies on the Nervous system (CISNe), Universidad Austral de Chile, Valdivia, Chile.
authors.forename: Aníbal I
authors.initials: AI
authors.lastname: Acuña
authors.affiliation: Instituto de Bioquímica y Microbiología, Facultad de Ciencias, Universidad Austral de Chile, Valdivia, Chile; Center for Interdisciplinary Studies on the Nervous system (CISNe), Universidad Austral de Chile, Valdivia, Chile.
authors.forename: Andrea
authors.initials: A
authors.lastname: Riveros
authors.affiliation: Instituto de Bioquímica y Microbiología, Facultad de Ciencias, Universidad Austral de Chile, Valdivia, Chile; Center for Interdisciplinary Studies on the Nervous system (CISNe), Universidad Austral de Chile, Valdivia, Chile.
authors.forename: María Paz
authors.initials: MP
authors.lastname: Miró
authors.affiliation: Instituto de Bioquímica y Microbiología, Facultad de Ciencias, Universidad Austral de Chile, Valdivia, Chile; Center for Interdisciplinary Studies on the Nervous system (CISNe), Universidad Austral de Chile, Valdivia, Chile.
authors.forename: Eduardo
authors.initials: E
authors.lastname: Papic
authors.affiliation: Instituto de Bioquímica y Microbiología, Facultad de Ciencias, Universidad Austral de Chile, Valdivia, Chile; Center for Interdisciplinary Studies on the Nervous system (CISNe), Universidad Austral de Chile, Valdivia, Chile.
authors.forename: Felipe A
authors.initials: FA
authors.lastname: Beltrán
authors.affiliation: Intellectual and Developmental Disabilities Research Center, Semel Institute for Neuroscience and Human Behavior, Brain Research Institute, The David Geffen School of Medicine, UCLA, Los Angeles, USA and.
authors.forename: Carlos
authors.initials: C
authors.lastname: Cepeda
authors.affiliation: Instituto de Bioquímica y Microbiología, Facultad de Ciencias, Universidad Austral de Chile, Valdivia, Chile.
authors.forename: Ilona I
authors.initials: II
authors.lastname: Concha
authors.affiliation: Center for Interdisciplinary Studies on the Nervous system (CISNe), Universidad Austral de Chile, Valdivia, Chile; Instituto de Fisiología, Facultad de Medicina, Universidad Austral de Chile, Valdivia, Chile.
authors.forename: Sebastián
authors.initials: S
authors.lastname: Brauchi
authors.affiliation: Instituto de Bioquímica y Microbiología, Facultad de Ciencias, Universidad Austral de Chile, Valdivia, Chile; Center for Interdisciplinary Studies on the Nervous system (CISNe), Universidad Austral de Chile, Valdivia, Chile. Electronic address: macastro@uach.cl.
authors.forename: Maite A
authors.initials: MA
authors.lastname: Castro
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D001205:Ascorbic Acid / Q000494:pharmacology; D015153:Blotting, Western; D002462:Cell Membrane / Q000378:metabolism; D002478:Cells, Cultured; D004195:Disease Models, Animal; D004734:Energy Metabolism / Q000187:drug effects*; D005260:Female; D005455:Fluorescent Antibody Technique; D005947:Glucose / Q000378:metabolism; D051274:Glucose Transporter Type 3 / Q000235:genetics / Q000378:metabolism*; D006816:Huntington Disease / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D008297:Male; D051379:Mice; D009474:Neurons / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D000975:Antioxidants; D051274:Glucose Transporter Type 3; D012333:RNA, Messenger; D005947:Glucose; D001205:Ascorbic Acid
keywords: Ascorbic acid; Astrocyte-neuron lactate shuttle (ANLS); Brain energy metabolism; Vitamin C