TY - JOUR
T1 - Arachidonic acid-induced oxidative injury to cultured spinal cord neurons
AU - Toborek, Michal
AU - Malecki, Andrzej
AU - Garrido, Rosario
AU - Mattson, Mark P.
AU - Hennig, Bernhard
AU - Young, Byron
PY - 1999
Y1 - 1999
N2 - 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-KB (NF-κB), and cell viability. AA treatment increased 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.
AB - 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-KB (NF-κB), and cell viability. AA treatment increased 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.
KW - Antioxidants
KW - Free fatty acids
KW - Oxidative stress
KW - Spinal cord trauma
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U2 - 10.1046/j.1471-4159.1999.0730684.x
DO - 10.1046/j.1471-4159.1999.0730684.x
M3 - Article
C2 - 10428065
AN - SCOPUS:0032797822
SN - 0022-3042
VL - 73
SP - 684
EP - 692
JO - Journal of Neurochemistry
JF - Journal of Neurochemistry
IS - 2
ER -