OBJECTIVE Previously we demonstrated the neuroprotective effect of 5-lipoxygenase(5-LOX)inhibitor as well as cysteinyl leukotriene receptor 1(Cys LT1)antagoniston rotenone-induced microglial activation and neuronal de...OBJECTIVE Previously we demonstrated the neuroprotective effect of 5-lipoxygenase(5-LOX)inhibitor as well as cysteinyl leukotriene receptor 1(Cys LT1)antagoniston rotenone-induced microglial activation and neuronal death.In this study,we determined the effects of 5-LOX inhibitor zileuton and Cys LT1 antagonist montelukast on neurotoxicity induced by 1-methyl-4-phenylpyridine(MPP+)in an in vitro model of Parkinson disease(PD).METHODS The neurotoxicity of MPP+,a neurotoxin relevant to PD,on the PC12 cells was measured by MTT assay,lactate dehydrogenase(LDH)release and double fluorescence staining with Hoechst/propidiumiodide(PI).The protective effects of 5-LOX inhibitor zileuton and Cys LT1 antagonist montelukast were investigated by the above methods.RESULTS We found that exposure of PC12 cells to MPP+led to a reduced cell viability and an increased level of LDH in a concentration-dependent manner.Pretreatment with zileuton and montelukast significantly attenuated viability loss and LDH release in MPP+-treated PC12 cells.Furthermore,MPP+increasednecrotic cell death in PC12 cells.Administration of montelukast significantly decreased MPP+-induced cell necrosis in PC12 cells.CONCLUSION The 5-LOX inhibitor zileuton and Cys LT1 antagonist montelukast have a neuroprotective effects on MPP+-induced neurotoxicity in PC12 cells.The 5-LOX inhibitor and Cys LT1 antagonist might raise a possibility as potential therapeutic agent for PD and other inflammation-related the central nervous system disorders.展开更多
Objective Aquaporin-4 （AQP4）, the main water channel protein in the brain, plays a critical role in water homeostasis and brain edema. Here, we investigated its role in the inflammatory responses after focal cerebra...Objective Aquaporin-4 （AQP4）, the main water channel protein in the brain, plays a critical role in water homeostasis and brain edema. Here, we investigated its role in the inflammatory responses after focal cerebral ischemia. Methods In AQP4-knockout （KO） and wild-type mice, focal cerebral ischemia was induced by 30 rain of middle cerebral arterial occlusion （MCAO）. Ischemic neuronal injury and cellular inflammatory responses, as well as the expression and localization of cysteinyl leukotriene CysLT2 and CysLT~ receptors, were determined at 24 and 72 h after MCAO. Results AQP4-KO mice showed more neuronal loss, more severe microglial activation and neutrophil infiltration, but less astrocyte proliferation in the brain after MCAO than wild-type mice. In addition, the protein levels of both CysLT1 and CysLT2 receptors were up-regulated in the ischemic brain, and the up-regulation was more pronounced in AQP4-KO mice. The CysLT1 and CysLT2 receptors were primarily localized in neurons, microglia and neutrophils; those localized in microglia and neutrophils were enhanced in AQP4-KO mice. Conclusion AQP4 may play an inhibitory role in postischemic inflammation.展开更多
基金The project supported National Natural Science Foundation of China(81273491)the Zhejiang Provincial Natural Science Foundation(LY12H31010)
文摘OBJECTIVE Previously we demonstrated the neuroprotective effect of 5-lipoxygenase(5-LOX)inhibitor as well as cysteinyl leukotriene receptor 1(Cys LT1)antagoniston rotenone-induced microglial activation and neuronal death.In this study,we determined the effects of 5-LOX inhibitor zileuton and Cys LT1 antagonist montelukast on neurotoxicity induced by 1-methyl-4-phenylpyridine(MPP+)in an in vitro model of Parkinson disease(PD).METHODS The neurotoxicity of MPP+,a neurotoxin relevant to PD,on the PC12 cells was measured by MTT assay,lactate dehydrogenase(LDH)release and double fluorescence staining with Hoechst/propidiumiodide(PI).The protective effects of 5-LOX inhibitor zileuton and Cys LT1 antagonist montelukast were investigated by the above methods.RESULTS We found that exposure of PC12 cells to MPP+led to a reduced cell viability and an increased level of LDH in a concentration-dependent manner.Pretreatment with zileuton and montelukast significantly attenuated viability loss and LDH release in MPP+-treated PC12 cells.Furthermore,MPP+increasednecrotic cell death in PC12 cells.Administration of montelukast significantly decreased MPP+-induced cell necrosis in PC12 cells.CONCLUSION The 5-LOX inhibitor zileuton and Cys LT1 antagonist montelukast have a neuroprotective effects on MPP+-induced neurotoxicity in PC12 cells.The 5-LOX inhibitor and Cys LT1 antagonist might raise a possibility as potential therapeutic agent for PD and other inflammation-related the central nervous system disorders.
基金supported by the National Natural Science Foundation of China(81273491, 81072618,30772561 and 30873053)the Natural Science Foundation of Zhejiang Province,China(Y2090069)+1 种基金the"Qianjiang Rencai Research Plan"of Zhejiang Province China(2010R10055)the Fundamental Research Funds for the Central Universities,China(2009QNA7008)
文摘Objective Aquaporin-4 （AQP4）, the main water channel protein in the brain, plays a critical role in water homeostasis and brain edema. Here, we investigated its role in the inflammatory responses after focal cerebral ischemia. Methods In AQP4-knockout （KO） and wild-type mice, focal cerebral ischemia was induced by 30 rain of middle cerebral arterial occlusion （MCAO）. Ischemic neuronal injury and cellular inflammatory responses, as well as the expression and localization of cysteinyl leukotriene CysLT2 and CysLT~ receptors, were determined at 24 and 72 h after MCAO. Results AQP4-KO mice showed more neuronal loss, more severe microglial activation and neutrophil infiltration, but less astrocyte proliferation in the brain after MCAO than wild-type mice. In addition, the protein levels of both CysLT1 and CysLT2 receptors were up-regulated in the ischemic brain, and the up-regulation was more pronounced in AQP4-KO mice. The CysLT1 and CysLT2 receptors were primarily localized in neurons, microglia and neutrophils; those localized in microglia and neutrophils were enhanced in AQP4-KO mice. Conclusion AQP4 may play an inhibitory role in postischemic inflammation.
