title: Lipoic acid increases glutamate uptake, glutamine synthetase activity and glutathione content in C6 astrocyte cell line.
abstract: Alpha lipoic acid (LA) is a sulfhydryl compound, used as dietary supplement and to treat a variety of conditions associated to oxidative stress. Glial cells are key modulators of neuroprotection. We show here that LA modulates specific glial parameters in C6 astrocyte cell line, such as glutamate uptake, glutamine synthetase (GS) activity and glutathione content, commonly associated with the protective role of glial cells. LA (10 and 50μM) after 24h of treatment significantly decreased the formation of reactive oxygen species (ROS) and nitric oxide (NO) levels, and increased glutamate uptake (up to 20%), GS activity (25%) and GSH content (up to 40%). LA increase glutamate uptake probably by decreasing oxidizing conditions and/or by mechanism dependent of protein kinase C (PKC). In contrast, high concentrations of LA (1000μM) decreased these glial functions. Moreover, this concentration increased ROS production and NO levels. In summary, these findings show that low doses of LA were able to modulate glial functions and it appears to have remarkable therapeutic potential in neurological diseases involving oxidative stress by improving glutamatergic metabolism.
authors.affiliation: Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil.
authors.forename: Juliana
authors.initials: J
authors.lastname: Kleinkauf-Rocha
authors.forename: Larissa Daniele
authors.initials: LD
authors.lastname: Bobermin
authors.forename: Priscila de Mattos
authors.initials: Pde M
authors.lastname: Machado
authors.forename: Carlos-Alberto
authors.initials: CA
authors.lastname: Gonçalves
authors.forename: Carmem
authors.initials: C
authors.lastname: Gottfried
authors.forename: André
authors.initials: A
authors.lastname: Quincozes-Santos
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000187:drug effects* / Q000378:metabolism; D002460:Cell Line; D005974:Glutamate-Ammonia Ligase / Q000378:metabolism*; D018698:Glutamic Acid / Q000378:metabolism*; D005978:Glutathione / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D008063:Thioctic Acid / Q000494:pharmacology*
chemical_list: D017382:Reactive Oxygen Species; D009569:Nitric Oxide; D018698:Glutamic Acid; D008063:Thioctic Acid; D005974:Glutamate-Ammonia Ligase; D005978:Glutathione