Lipoic acid increases glutamate uptake, glutamine synthetase activity and glutathione content in C6 astrocyte cell line

Int J Dev Neurosci. 2013 May;31(3):165-70. doi: 10.1016/j.ijdevneu.2012.12.006. Epub 2012 Dec 31.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Astrocytes / drug effects*
  • Astrocytes / metabolism
  • Cell Line
  • Glutamate-Ammonia Ligase / metabolism*
  • Glutamic Acid / metabolism*
  • Glutathione / metabolism*
  • Nitric Oxide / metabolism
  • Oxidative Stress / drug effects
  • Rats
  • Reactive Oxygen Species / metabolism
  • Thioctic Acid / pharmacology*

Substances

  • Reactive Oxygen Species
  • Nitric Oxide
  • Glutamic Acid
  • Thioctic Acid
  • Glutamate-Ammonia Ligase
  • Glutathione