Arachidonic Acid‐Induced Oxidative Injury to Cultured Spinal Cord Neurons

• Published in: Journal of neurochemistry 1999-08, Vol.73 (2), p.684-692
• Main Authors: Toborek, Michal, Malecki, Andrzej, Garrido, Rosario, Mattson, Mark P., Hennig, Bernhard, Young, Byron
• Format: Article
• Language: English
• Subjects: Animals; Antioxidants; Arachidonic Acid - toxicity; Biological and medical sciences; Calcium - metabolism; Cell Survival - drug effects; Cells, Cultured; Dose-Response Relationship, Drug; Enhancer Elements, Genetic - physiology; Fatty Acids, Nonesterified - metabolism; Female; Fetus - cytology; Free fatty acids; Injuries of the nervous system and the skull. Diseases due to physical agents; Medical sciences; Mice; Neurons - cytology; Neurons - enzymology; NF-kappa B - genetics; NF-kappa B - metabolism; Oxidative stress; Oxidative Stress - physiology; Phosphatidylcholines - metabolism; Phosphatidylethanolamines - metabolism; Phosphatidylinositols - metabolism; Pregnancy; Spinal Cord - cytology; Spinal Cord Injuries - metabolism; Spinal cord trauma; Superoxide Dismutase - metabolism; Traumas. Diseases due to physical agents
• ISSN: 0022-3042; 1471-4159
• DOI: 10.1046/j.1471-4159.1999.0730684.x

: Spinal cord trauma can cause a marked release of free fatty acids, in particular, arachidonic acid (AA), from cell membranes. Free fatty acids, and AA by itself, may lead to secondary damage to spinal cord neurons. To study this hypothesis, cultured spinal cord neurons were exposed to increasing concentrations of AA (0.01‐10 μM). AA‐induced injury to spinal cord neurons was assessed by measurements of cellular oxidative stress, intracellular calcium levels, activation of nuclear factor‐κB (NF‐κB), and cell viability. AA treatment increased cell intracellular calcium concentrations and decreased cell viability. Oxidative stress increased significantly in neurons exposed to 1 and 10 μM AA. In addition, AA treatment activated NF‐κB and decreased levels of the inhibitory subunit, IκB. It is interesting that manganese superoxide dismutase protein levels and levels of intracellular total glutathione increased in neurons exposed to this fatty acid for 24 h, consistent with a compensatory response to increased oxidative stress. These results strongly support the hypothesis that free fatty acids contribute to the tissue injury observed following spinal cord trauma.