Effect of 1400W, an inhibitor of inducible nitric oxide synthetase, on blocking the toxicity of lipopolysaccharide-induced activated microglia to preoligodendrocytes

OBJECTIVE: To explore the toxicity of LPS-induced activated microglia to preoligodendrocytes (preOLs) and the effect of 1400W, a selective inhibitor of inducible nitric oxide synthetase (iNOS), on the blockage of the toxicity

Bibliographische Detailangaben
Veröffentlicht in:Zhonghua er ke za zhi = Chinese journal of pediatrics. - 1960. - 47(2009), 7 vom: 02. Juli, Seite 537-43
1. Verfasser: He, Ya-Fang (VerfasserIn)
Weitere Verfasser: Chen, Hui-Jin, Qian, Long-Hua, Chen, Guan-Yi
Format: Aufsatz
Sprache:Chinese
Veröffentlicht: 2009
Zugriff auf das übergeordnete Werk:Zhonghua er ke za zhi = Chinese journal of pediatrics
Schlagworte:English Abstract Journal Article Research Support, Non-U.S. Gov't Amidines Benzylamines Lipopolysaccharides N-(3-(aminomethyl)benzyl)acetamidine Nitric Oxide 31C4KY9ESH Nitric Oxide Synthase EC 1.14.13.39
Beschreibung
Zusammenfassung:OBJECTIVE: To explore the toxicity of LPS-induced activated microglia to preoligodendrocytes (preOLs) and the effect of 1400W, a selective inhibitor of inducible nitric oxide synthetase (iNOS), on the blockage of the toxicity
METHODS: Co-cultured microglia and preOLs obtained from two-day-old Sprague-Dawley (SD) rats were divided into three groups: co-culture control group, co-culture LPS group and co-culture LPS plus 1400W group. After cultured cells were induced by LPS (100 ng/ml) for 48 hours, the concentration of nitric oxide (NO) was measured by nitric acid-oeoxidize-colorimetry, the level of peroxynitrite (ONOO(-)) was determined by immunocytochemistry, and the synthetic level of iNOS was detected by Western blotting, respectively. The morphologic observation of apoptotic preOLs stained with Hoechst 33342/PI and the apoptotic rate of preOLs detected by flow cytometry were processed simultaneously. Data were analyzed with SPSS 11.0 software
RESULTS: Compared to co-culture control group, there was significant increase in levels of NO [(82.27+/-3.41) micromol/L vs. (167.86+/-9.87) micromol/L, t=8.593, P<0.01], ONOO(-)[(6.14+/-1.27) x 10(7)/L vs. (34.38+/-7.75) x 10(7)/L, t=5.892, P<0.01], and iNOS [(0.18+/-0.027) vs. (0.79+/-0.068), t=9.26, P<0.01] induced by LPS in co-culture LPS group, and with a higher apoptotic rate of preOLs [(6.73+/-1.39)% vs. (24.77+/-2.05)%, t=12.619, P<0.01]. However, all levels of NO [(69.55+/-5.07) micromol/L, t=8.896, P<0.01], ONOO(-) [(10.33+/-3.47) x 10(7)/L, t=14.96, P<0.01] and iNOS (0.35+/-0.042, t=5.506, P<0.01) decreased significantly with the use of 1400W at a dose of 10 micromol/L in co-culture LPS plus 1400W group, and the apoptotic rate of preOLs [(11.8+/-2.06)%, t=7.715, P<0.01] was also reduced evidently
CONCLUSIONS: NO, ONOO(-) and iNOS, etc. play important roles in the death pathway of preOLs induced by LPS. 1400W can block effectively the toxicity of LPS-activated microglia toxicity to preOLs through inhibiting iNOS selectively and reducing the production of NO and ONOO(-), and improve the survival rate of preOLs
Beschreibung:Date Completed 02.12.2010
Date Revised 07.06.2016
published: Print
Citation Status MEDLINE
ISSN:0578-1310