AIM: To evaluate the effects of butein on inflammatory cytokines, matrix metalloproteinase-9(MMP-9), andcolitis in interleukin(IL)-10-/- mice.METHODS: To synchronize colitis, 8- to 10-wk-old IL-10-/- mice were fed pel...AIM: To evaluate the effects of butein on inflammatory cytokines, matrix metalloproteinase-9(MMP-9), andcolitis in interleukin(IL)-10-/- mice.METHODS: To synchronize colitis, 8- to 10-wk-old IL-10-/- mice were fed pellet-chow containing piroxicam for 2 wk. Subsequently, phosphate-buffered saline or butein(1 mg/kg per day, ip) was injected for 4 wk. Histologic scores, inflammatory cytokines, MMP-9 and phosphorylated signal transducer and activator of transcription 3(p STAT3) expressions were analyzed in IL-10-/- mice and in Colo 205 cells.RESULTS: Butein reduced the colonic inflammatory score by > 50%. Expression levels of IL-6, IL-1β, interferon(IFN)-γ and MMP-9 were decreased in the colons of mice exposed to butein, whereas other inflammatory cytokines(IL-17 A, IL-21 and IL-22) were unchanged. Immunohistochemical staining for p STAT3 and MMP-9 was significantly decreased in the buteintreated groups compared with the controls. Butein inhibited IL-6-induced activation of STAT3 in Colo 205 cells.CONCLUSION: Butein ameliorated colitis in IL-10-/-mice by regulating IL-6/STAT3 and MMP-9 activation.展开更多
目的:探讨组蛋白变异体macroH2A(mH2A)和Butein共同作用GRP78蛋白通过丝裂原激活蛋白激酶(mitogen-activation protein kinase,MAPK)信号通路调控黑色素瘤的生物学行为。方法:采用免疫组织化学检测黑色素瘤和癌旁正常组织中mH2A和葡萄...目的:探讨组蛋白变异体macroH2A(mH2A)和Butein共同作用GRP78蛋白通过丝裂原激活蛋白激酶(mitogen-activation protein kinase,MAPK)信号通路调控黑色素瘤的生物学行为。方法:采用免疫组织化学检测黑色素瘤和癌旁正常组织中mH2A和葡萄糖调节蛋白78(glucose regulated protein of 78,GRP78)的表达情况;分析临床资料与mH2A和GRP78表达的关系;免疫共沉淀实验检测GRP78和mH2A蛋白的相互作用;Western印迹检测mH2A和GRP78的相关作用及Butein与mH2A之间的作用。Transwell试验检测mH2A的表达对黑色素瘤细胞侵袭能力的影响;划痕试验检测mH2A的表达对黑色素瘤细胞迁移能力的影响;Western印迹检测沉默mH2A后细胞外信号调节激酶1(ERK1)和MAPK/ERK激酶(MEK)蛋白的表达。结果:与癌旁正常组织相比,黑色素瘤组织中mH2A和GRP78表达明显降低(P<0.05);Butein可以增强mH2A的表达水平(P<0.05),mH2A可以调节GRP78蛋白的表达(P<0.05);沉默mH2A促进黑色素瘤A375细胞的侵袭迁移能力,上调MEK和ERK1蛋白的表达。结论:Butein可以增强mH2A靶向GRP78蛋白通过MAPK信号通路抑制黑色素瘤细胞的迁移和侵袭行为。展开更多
文摘目的:研究紫铆花素对PC12细胞氧化应激损伤的保护作用及对线粒体功能的影响。方法:将大鼠PC12细胞分为正常对照组、模型组、溶剂对照组(1‰二甲基亚砜)和紫铆花素高、中、低浓度组(2、1、0.5μmol/L)。后4组给予相应试剂/药物干预24 h后,除正常对照组外的其余组均以100 m U/mL葡萄糖氧化酶诱导氧化应激模型。培养4 h后,检测细胞存活率、凋亡率和细胞内活性氧(ROS)、丙二醛(MDA)、超氧化物歧化酶(SOD)、过氧化氢酶(CAT)、谷胱甘肽过氧化物酶(GSH-Px)、三磷酸腺苷(ATP)、白细胞介素1β(IL-1β)、肿瘤坏死因子α(TNF-α)水平或活性以及线粒体膜电位(MMP)变化。结果:与正常对照组比较,模型组细胞存活率和SOD、CAT、GSH-Px、ATP活性或水平均显著降低,凋亡率、ROS含量和MDA、IL-1β、TNF-α水平均显著增加(P<0.05或P<0.01),MMP明显降低。与模型组比较,溶剂对照组上述指标均无明显变化(P>0.05),紫铆花素高、中、低浓度组细胞存活率和SOD(除中、低浓度组外)、CAT、GSH-Px(除中、低浓度组外)、ATP(除低浓度组外)活性或水平均显著升高,凋亡率、ROS含量和MDA、IL-1β、TNF-α水平均显著降低(P<0.05或P<0.01),MMP明显增加。结论:紫铆花素可通过增强抗氧化酶活性,稳定线粒体功能,抑制氧化应激和炎症反应,增加能量生成,进而抑制神经细胞凋亡,最终发挥神经保护的作用。
基金Supported by Grants from the National Research Foundation of Korea,No.R1102452Korea University,No.K1220161by experimental techniques from the Core Laboratory for Convergent Translational Research of College of Medicine
文摘AIM: To evaluate the effects of butein on inflammatory cytokines, matrix metalloproteinase-9(MMP-9), andcolitis in interleukin(IL)-10-/- mice.METHODS: To synchronize colitis, 8- to 10-wk-old IL-10-/- mice were fed pellet-chow containing piroxicam for 2 wk. Subsequently, phosphate-buffered saline or butein(1 mg/kg per day, ip) was injected for 4 wk. Histologic scores, inflammatory cytokines, MMP-9 and phosphorylated signal transducer and activator of transcription 3(p STAT3) expressions were analyzed in IL-10-/- mice and in Colo 205 cells.RESULTS: Butein reduced the colonic inflammatory score by > 50%. Expression levels of IL-6, IL-1β, interferon(IFN)-γ and MMP-9 were decreased in the colons of mice exposed to butein, whereas other inflammatory cytokines(IL-17 A, IL-21 and IL-22) were unchanged. Immunohistochemical staining for p STAT3 and MMP-9 was significantly decreased in the buteintreated groups compared with the controls. Butein inhibited IL-6-induced activation of STAT3 in Colo 205 cells.CONCLUSION: Butein ameliorated colitis in IL-10-/-mice by regulating IL-6/STAT3 and MMP-9 activation.
文摘目的:探讨组蛋白变异体macroH2A(mH2A)和Butein共同作用GRP78蛋白通过丝裂原激活蛋白激酶(mitogen-activation protein kinase,MAPK)信号通路调控黑色素瘤的生物学行为。方法:采用免疫组织化学检测黑色素瘤和癌旁正常组织中mH2A和葡萄糖调节蛋白78(glucose regulated protein of 78,GRP78)的表达情况;分析临床资料与mH2A和GRP78表达的关系;免疫共沉淀实验检测GRP78和mH2A蛋白的相互作用;Western印迹检测mH2A和GRP78的相关作用及Butein与mH2A之间的作用。Transwell试验检测mH2A的表达对黑色素瘤细胞侵袭能力的影响;划痕试验检测mH2A的表达对黑色素瘤细胞迁移能力的影响;Western印迹检测沉默mH2A后细胞外信号调节激酶1(ERK1)和MAPK/ERK激酶(MEK)蛋白的表达。结果:与癌旁正常组织相比,黑色素瘤组织中mH2A和GRP78表达明显降低(P<0.05);Butein可以增强mH2A的表达水平(P<0.05),mH2A可以调节GRP78蛋白的表达(P<0.05);沉默mH2A促进黑色素瘤A375细胞的侵袭迁移能力,上调MEK和ERK1蛋白的表达。结论:Butein可以增强mH2A靶向GRP78蛋白通过MAPK信号通路抑制黑色素瘤细胞的迁移和侵袭行为。
