Neuroprotective effect of the stearic acid against oxidative stress via phosphatidylinositol 3-kinase pathway.
Stearic acid is a long-chain saturated fatty acid consisting of 18 carbon atoms without double bonds. In the present study, we reported the neuroprotective effects and mechanism of stearic acid on cortical or hippocampal slices insulted by oxygen-glucose deprivation, NMDA or hydrogen peroxide (H(2)O(2)) in vitro. Different types of models of brain slice injury in vitro were developed by 10 min of oxygen/glucose deprivation, 0.5 mM NMDA or 2 mM H(2)O(2), respectively. After 30 min of preincubation with stearic acid (3-30 microM), cortical or hippocampal slices were subjected to oxygen-glucose deprivation, NMDA or H(2)O(2). Then the tissue activities were evaluated by using the 2,3,5-triphenyltetrazolium chloride (TTC) method. Population spikes were recorded in randomly selected hippocampal slices. Stearic acid (3-30 microM) dose-dependently protected brain slices from oxygen-glucose deprivation, NMDA and H(2)O(2) insults. Its neuroprotective effect against H(2)O(2) insults can be completely blocked by wortmannin (inhibitor of PI3K) and partially blocked by H7 (inhibitor of PKC) or genistein (inhibitor of TPK). Treatment of cortical or hippocampal slices with 30 microM stearic acid resulted in a significant increase in PI3K activity at 5, 10, 30 and 60 min. These observations reveal that stearic acid can protect cortical or hippocampal slices against injury induced by oxygen-glucose deprivation, NMDA or H(2)O(2), and its neuroprotective effects are via phosphatidylinositol 3-kinase dependent mechanism.
Wang
Ze-Jian
ZJ
School of Pharmacy, Shanghai Jiao Tong University, Shanghai 200240, PR China.
Li
Guang-Mei
GM
Nie
Bao-Ming
BM
Lu
Yang
Y
Yin
Ming
M
D000818:Animals; D002540:Cerebral Cortex / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D004396:Coloring Agents / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005947:Glucose / Q000172:deficiency / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D002534:Hypoxia, Brain / Q000201:enzymology / Q000209:etiology / Q000517:prevention & control*; D008297:Male; D018696:Neuroprotective Agents / Q000494:pharmacology*; D009924:Organ Culture Techniques; D018384:Oxidative Stress; D010100:Oxygen / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013229:Stearic Acids / Q000494:pharmacology*; D013778:Tetrazolium Salts / Q000494:pharmacology
D004396:Coloring Agents; D018696:Neuroprotective Agents; D013229:Stearic Acids; D013778:Tetrazolium Salts; C031183:stearic acid; C009591:triphenyltetrazolium; D019869:Phosphatidylinositol 3-Kinases; D005947:Glucose; D010100:Oxygen