Abstract
Aim:
To observe the effects of stearic acid against oxidative stress in primary cultured cortical neurons.
Methods:
Cortical neurons were exposed to glutamate, hydrogen peroxide (H2O2), or NaN3 insult in the presence or absence of stearic acid. Cell viability of cortical neurons was determined by MTT assay and LDH release. Endogenous antioxidant enzymes activity[superoxide dismutases (SOD), glutathione peroxidase (GSH-Px), and catalase (CAT)] and lipid peroxidation in cultured cortical neurons were evaluated using commercial kits. {3-[1(p-chloro-benzyl)-5-(isopropyl)-3-t-butylthiondol-2-yl]-2,2-dimethylpropanoic acid, Na} [MK886; 5 μmol/L; a noncompetitive inhibitor of proliferator-activated receptor (PPAR)α], bisphenol A diglycidyl ether (BADGE; 100 μmol/L; an antagonist of PPARγ), and cycloheximide (CHX; 30 μmol/L, an inhibitor of protein synthesis) were tested for their effects on the neuroprotection afforded by stearic acid. Western blotting was used to determine the PPARγ protein level in cortical neurons.
Results:
Stearic acid dose-dependently protected cortical neurons against glutamate or H2O2 injury and increased glutamate uptake in cultured neurons. This protection was concomitant to the inhibition of lipid peroxidation and to the promotion activity of Cu/Zn SOD and CAT in cultured cortical neurons. Its neuroprotective effects were completely blocked by BADGE and CHX. After incubation with H2O2 for 24 h, the expression of the PPARγ protein decreased significantly (P<0.05), and the inhibitory effect of H2O2 on the expression of PPARγ can be attenuated by stearic acid.
Conclusion:
Stearic acid can protect cortical neurons against oxidative stress by boosting the internal antioxidant enzymes. Its neuroprotective effect may be mainly mediated by the activation of PPARγ and new protein synthesis in cortical neurons.
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Project supported by the Natural Science Foundation of Shanghai (No 03ZR14056).
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Wang, Zj., Liang, Cl., Li, Gm. et al. Stearic acid protects primary cultured cortical neurons against oxidative stress. Acta Pharmacol Sin 28, 315–326 (2007). https://doi.org/10.1111/j.1745-7254.2007.00512.x
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DOI: https://doi.org/10.1111/j.1745-7254.2007.00512.x
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