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Stearic acid protects primary cultured cortical neurons against oxidative stress 4
Author(s) -
WANG Zejian,
LIANG Cuiling,
LI Guangmei,
YU Caiyi,
YIN Ming
Publication year - 2007
Publication title -
acta pharmacologica sinica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.514
H-Index - 90
eISSN - 1745-7254
pISSN - 1671-4083
DOI - 10.1111/j.1745-7254.2007.00512.x
Subject(s) - oxidative stress , primary (astronomy) , cortical neurons , chemistry , stearic acid , reactive oxygen species , microbiology and biotechnology , pharmacology , biology , biochemistry , organic chemistry , physics , astronomy
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 (H 2 O 2 ), or NaN 3 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 H 2 O 2 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 H 2 O 2 for 24 h, the expression of the PPARγ protein decreased significantly ( P <0.05), and the inhibitory effect of H 2 O 2 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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