Stearic acid protects primary cultured cortical neurons against oxidative stress.
OBJECTIVE
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-chlorobenzyl)- 5-(isopropyl)-3-t-butylthiondol-2-yl]-2,2-dimethylpropanoic acid, Na} [MK886; 5 micromol/L; a noncompetitive inhibitor of proliferator-activated receptor (PPAR) alpha], bisphenol A diglycidyl ether (BADGE; 100 micromol/L; an antagonist of PPAR gamma), and cycloheximide (CHX; 30 micromol/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 PPAR gamma 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 PPAR gamma protein decreased significantly (P<0.05), and the inhibitory effect of H2O2 on the expression of PPAR gamma can be attenuated by stearic acid.


CONCLUSIONS
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 PPAR gamma and new protein synthesis in cortical neurons.
Wang
Ze-Jian
ZJ
School of Pharmacy, Shanghai Jiao Tong University, Shanghai 200030, China.
Liang
Cui-Ling
CL
Li
Guang-Mei
GM
Yu
Cai-Yi
CY
Yin
Ming
M
D000818:Animals; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology* / Q000187:drug effects; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D005260:Female; D018698:Glutamic Acid / Q000378:metabolism / Q000633:toxicity; D006861:Hydrogen Peroxide / Q000037:antagonists & inhibitors / Q000633:toxicity; D008024:Ligands; D015227:Lipid Peroxidation / Q000187:drug effects; D009474:Neurons / Q000187:drug effects*; D018696:Neuroprotective Agents; D018384:Oxidative Stress / Q000187:drug effects*; D047495:PPAR gamma / Q000187:drug effects; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley; D019810:Sodium Azide / Q000037:antagonists & inhibitors / Q000633:toxicity; D013229:Stearic Acids / Q000494:pharmacology*
D018691:Excitatory Amino Acid Antagonists; D008024:Ligands; D018696:Neuroprotective Agents; D047495:PPAR gamma; D013229:Stearic Acids; D018698:Glutamic Acid; C031183:stearic acid; D019810:Sodium Azide; D006861:Hydrogen Peroxide