姜黄素对多巴胺能细胞的保护作用及其机制的实验研究
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摘要
目的探讨姜黄素(Cur)对鱼藤酮(Ro)致PC12细胞损伤的保护作用及其机制。
方法用鱼藤酮建立PC12细胞损伤模型；姜黄素进行干预。用四氮唑盐(MTT)比色法检测细胞增殖活力；苏木素、伊红染色观察细胞形态学变化；比色法检测细胞内总超氧化物歧化酶(SOD)的活性；DCFH--DA染色检测细胞内活性氧类物质(ROS)水平；流式细胞术(Annexin-FITC／PI双染法)检测PC12细胞的凋亡。
结果0.5μmol/L—1.0μmol/L姜黄素均可减轻0.1μmol/L鱼藤酮对PC12细胞增殖活力的抑制；明显减轻了细胞损伤的形态学改变；明显增加了PC12细胞内SOD的活性；明显降低了PC12细胞内ROS的含量、明显抑制了鱼藤酮对PC12细胞凋亡的诱导作用。
结论：姜黄素可拮抗鱼藤酮致PC12细胞的损伤,其机制可能与清除细胞内ROS,诱导抗氧化酶的活性有关。
目的：探讨姜黄素(Curcumin)对α-突触核蛋白(α-synuclein)聚集的影响,及其拮抗鱼藤酮(Ro)诱导的PC12细胞损伤的作用机制。
方法：选用大鼠嗜铬细胞瘤株PC12细胞,利用鱼藤酮诱导其损伤建立帕金森病细胞模型,利用姜黄素进行干预；采用MTT法检测细胞活力、荧光酶标仪检测蛋白酶体水解酶活性、Western blotting法检测α-突出核蛋白表达、免疫荧光法检测细胞内α-突出核蛋白聚集、流式细胞仪检测PC12细胞凋亡。
结果：鱼藤酮组PC12细胞活力及蛋白酶体水解酶活性明显降低,α-突出核蛋白表达和聚集以及细胞凋亡率明显增加；经0.5、1.0、5.0、10μmol/L各浓度姜黄素预处理4h后与0.1μmol/L鱼藤酮共同孵育PC12细胞24h,0.5和1.0μmol/L的姜黄素使细胞活力以及蛋白酶体水解酶活性明显升高、α-突出核蛋白的表达和聚集明显减少、细胞凋亡率明显降低；5.0和10μmol/L姜黄素对鱼藤酮的拮抗作用明显减弱,细胞活力和蛋白酶体水解酶活性、以及细胞凋亡率与鱼藤酮组比较均无明显差异。
结论：低浓度姜黄素能够通过诱导PC12细胞蛋白酶体水解酶活性、抑制α-突出核蛋白的表达和聚集,从而拮抗鱼藤酮诱导的PC12细胞的损伤。
目的：探讨姜黄素(curcumin,Cur)通过诱导热休克蛋白(Hsp70)高表达、抑制α-突触核蛋白的异常表达和聚集、促进蛋白酶体系统降解异常α-突触核蛋白(a-synuclein)对多巴胺能细胞的保护作用
方法：选用大鼠嗜铬细胞瘤株PC12细胞,利用鱼藤酮诱导其损伤建立帕金森病细胞模型,利用姜黄素进行干预；采用MTT法检测细胞活力、荧光酶标仪检测蛋白酶体水解酶活性、Western blotting法检测Hsp70和α-突出核蛋白的表达、免疫荧光法检测细胞内Hsp70的表达和α-突出核蛋白的聚集。
结果：鱼藤酮组PC12细胞活力及蛋白酶体水解酶活性明显降低,Hsp70的表达轻度增加、α-突出核蛋白表达和聚集明显增加；经不同浓度姜黄素预处理4h后与0.1μmol/L鱼藤酮共同孵育PC12细胞24h,与鱼藤酮组比较,0.5μmol/L和1.0μmol/L的姜黄素使细胞活力以及蛋白酶体水解酶活性明显升高、Hsp70表达明显升高,α-突出核蛋白的表达和聚集明显减少；5.0μmol/L和10μmol/L姜黄素对鱼藤酮的拮抗作用明显减弱,细胞活力与鱼藤酮组比较均无明显差异(P<0.05),胰蛋白酶、多肽-谷氨酰多肽水解酶活性与鱼藤酮组比较均无明显差异(P<0.05)、10μmol/L姜黄素组糜蛋白酶样水解酶活性进一步降低,与鱼藤酮组比较有极显著性差异(P<0.01)。
结论：低浓度姜黄素能够通过诱导PC12细胞表达Hsp70、诱导蛋白酶体水解酶活性、进而抑制α-突出核蛋白的表达和聚集,从而拮抗鱼藤酮诱导的PC12细胞的损伤。
目的：探讨小胶质细胞在多巴胺能细胞损伤中的作用,以及姜黄素通过抑制小胶质细胞反应保护多巴胺能细胞的机制。
方法：选用大鼠嗜铬细胞瘤株PC12细胞,利用鱼藤酮诱导其损伤建立帕金森病细胞模型,用姜黄素预处理4h的BV-2细胞再经鱼藤酮处理4h后的细胞上清作为条件培养液(Microglia conditioned medium with Curcumin,MCMC),处理PC12细胞,并设空白对照组。应用四甲基偶氮唑盐法(MTT法)检测细胞活力；DCFH-DA染色检测BV-2细胞内活性氧类物质(ROS)水平；磷脂结合蛋白(Annexin V)-碘化丙啶(PI)双染色流式细胞仪检测PC12细胞凋亡。Western blotting法检测NADPH氧化酶P47-phox亚基蛋白在BV-2细胞膜上的表达。
结果：与对照组组相比,姜黄素预处理的BV-2细胞,其ROS水平降低(P<0.01)；受MCMC处理的PC12细胞,细胞活力增加,细胞凋亡率降低(P<0.01)。而单独用5nM鱼藤酮作用于PC12细胞,其存活率及凋亡率与空白组相比无明显差别(P>0.05)。鱼藤酮诱导BV-2细胞激活后,结合与BV-2细胞膜的NADPH氧化酶P47-phox亚基蛋白明显增加(P<0.01),姜黄素预处理使结合与BV-2细胞膜的NADPH氧化酶P47-phox亚基蛋白明显降低(P<0.05)。
结论：鱼藤酮激活小胶质细胞NADPH氧化酶产生ROS,损伤多巴胺能细胞。姜黄素通过抑制小角质细胞内NADPH氧化酶的激活,减少ROS的产生,从而保护多巴胺能细胞。
Abstract objective to investigate the cytoprotection of curcumin against rotenone-induced injury and the molecular mechanisms underlying in PC12 cells.
Methods:the insulted mode of PC 12 Cells was established with rotenone (Ro),cell viability was determined using MTT reduction assay;the content of reactive oxygen species(ROS) was detected with the method of DCFH-DA staining,chromatometry to detect the total activity of SOD;DCFH-DA staining to measure the level of intracellular ROS;flow cytometric analysis to survey the rate of cell apoptosis
Results:0.1μmol/L-1.0μmol/L Curcumin significantly decreased the inhibitory rate of Rotenone on the growth of PC 12 cells for 24h; 0.1μmol/L-1.0μmol/L Curcumin significantly ameliorate the changes in the morphology of PC 12 cells;increased the activities of intracellular SOD;decreased the production of intracellular ROS and inhibited the apoptosis of PC 12 cells induced by Rotenone for 24h.
Conclusion:Curcumin can resist rotenone-induced cytotoxicity probably by the mechanism of scavenging intracellular ROS and increasing the activity of antioxidase.
Purpose to investigate the effect of Curcumin on aggregtion of alph-synuclein and its mechanism to resist the Rotenone-induced injury to PC 12 cells.
Methods the cellular mode of parkinson's disease was established by adoption of rat pheochromocytoma strain PC12 cells and utilization of Rotenone to induce injury to them;Cell viability was assessed with MTT,Enzymatic activity of three hydrolases in proteasome was measured by detection of the fluorophore of various cleavaged synthetic fluorogenic peptides;The expression and aggregation of a-synuclein in PC12 cells was observed by Western blot and immunofluorescence respectively and cell apoptosis by flow cytometry.
Results Cell viability and activity of proteasome of Rotenone group were decreased dramatically;The expression and aggregation of a-synuclein and cell apotosis of Rotenone group increased apparently.0.5μmol/L and 1.0μmol/L Curcumin allowed Cell viability and activity of proteasome of PC 12 cells to increase significantly after co-incubation of Curcumin-pretreated PC12 cells with Ro for 24h and the resistant role of 5.0μmol/L and 10μmol/L Curcumin on the injury of Ro-induced PC12 cells decreased apparantly.
Conclusion low concentrion of Curcumin was able to induce the activity of proteasome and inhibit the expression and aggregation of a-synuclein in PC12 cells and thereby to alleviate the injury of Rotenone-induced PC 12 cells.
Abstract:To explore the protective effects of curcumin on dopaminergic cells by inducing the expression of heat shock protein70(Hsp70), inhibiting anormal expression and aggregation of a-synuclein and promoting proteasome system to degrade abnomal a-synuclein.
Methods:The cellular model for overexpressing a-synuclein was established by adoption of rat pheochromocytoma strain PC 12 cells treated with Rotenone.Cell viability was assessed with MTT,Enzymatic activity of three hydrolases in proteasome was measured by detection of the fluorophore of various cleavaged synthetic fluorogenic peptides;Western blot was used to dectect the expression of Hsp70 and a-synuclein;immunofluorescence to observe their expression andα-synuclein aggregation.
Results:At Rotenone group,cell viability、activity of proteasome were decreased dramatically(P<0.01),the expression level of Hsp70 and a-synuclein were increased significantly(P<0.01).Pretreatment with 0.5μmol/L and 1.0μmol/L Curcumin allowed cell viability,activity of proteasome in PC12 cells to increase significantly after co-incubation with Rotenone for 24h campared with Rotenone group(P<0.01),the expression level of Hsp70 to incease significantly(P<0.05,P<0.01 respectively),and significantly reduce a-synuclein expression (P<0.05) and aggregation;The protection of 5.0μmol/L and 10μmol/L Curcumin against the injury of Ro-induced PC12 cells decreased apparantly. Cell viability, activity of three hydrolases in proteasome are not significantly different from those of Rotenone group (P>0.05).
Conclusion low concentrion of Curcumin was able to induce higher expression of Hsp70 and the activity of proteasome and therefore inhibit the anormal expression and aggregation of a-synuclein in PC 12 cells and thereby to alleviate the injury of Rotenone-induced PC 12 cells.
Objective:To explore the effects of microglia on the impairment of dopaminergic cells and the mechanisms of Curcumin's protective effects on them by inhibitting microglia activation.
Methods:The cellular model of PD was established by adoption of rat pheochromocytoma strain PC12 cells treated with Rotenone,PC12 cells were treated with the medium from Curcumin-pretreated-BV-2 cells which were conditioned with Rotenone,and the blank control group was established.Cell viability was assessed with MTT;DCFH-DA staining was used to measure the level of intracellular ROS in BV-2 cells;flow cytometric analysis to survey the rate of cell apoptosis;Western blot was used to dectect the level of NADPH oxidase combining with membrane of BV-2 cell.
Results:Compared with the control group,the level of ROS in Curcumin-pretreated-BV-2 cells groups was decreased(P<0.01);Cell viability of PC 12 cells treated with MCMC was increased and the rate of apoptosis of them was decreased(P<0.01).The cell viability and rate of apoptosis of PC12 cells treated only with 5nM Rotenone were not different with those of blank control group(P>0.05).The level of NADPH oxidase P47-phox-combined with BV-2 cellular membrane of BV-2 activated by Rotenone was increased significantly(P <0.01),and the pretreatment of BV-2 cells with Curcumin made the level of NADPH oxidase P47-phox-combined with BV-2 cellular membrane decline significantly(P< 0.05)
Results:Microglia in which NADPH oxidase was activated by Rotenone impair dopaminergic cells by producing ROS.Curcumin protects dopaminergic cells by inhibitting activation of NADPH oxidase in microglia and decreasing the production of ROS.
方法用鱼藤酮建立PC12细胞损伤模型；姜黄素进行干预。用四氮唑盐(MTT)比色法检测细胞增殖活力；苏木素、伊红染色观察细胞形态学变化；比色法检测细胞内总超氧化物歧化酶(SOD)的活性；DCFH--DA染色检测细胞内活性氧类物质(ROS)水平；流式细胞术(Annexin-FITC／PI双染法)检测PC12细胞的凋亡。
结果0.5μmol/L—1.0μmol/L姜黄素均可减轻0.1μmol/L鱼藤酮对PC12细胞增殖活力的抑制；明显减轻了细胞损伤的形态学改变；明显增加了PC12细胞内SOD的活性；明显降低了PC12细胞内ROS的含量、明显抑制了鱼藤酮对PC12细胞凋亡的诱导作用。
结论：姜黄素可拮抗鱼藤酮致PC12细胞的损伤,其机制可能与清除细胞内ROS,诱导抗氧化酶的活性有关。
目的：探讨姜黄素(Curcumin)对α-突触核蛋白(α-synuclein)聚集的影响,及其拮抗鱼藤酮(Ro)诱导的PC12细胞损伤的作用机制。
方法：选用大鼠嗜铬细胞瘤株PC12细胞,利用鱼藤酮诱导其损伤建立帕金森病细胞模型,利用姜黄素进行干预；采用MTT法检测细胞活力、荧光酶标仪检测蛋白酶体水解酶活性、Western blotting法检测α-突出核蛋白表达、免疫荧光法检测细胞内α-突出核蛋白聚集、流式细胞仪检测PC12细胞凋亡。
结果：鱼藤酮组PC12细胞活力及蛋白酶体水解酶活性明显降低,α-突出核蛋白表达和聚集以及细胞凋亡率明显增加；经0.5、1.0、5.0、10μmol/L各浓度姜黄素预处理4h后与0.1μmol/L鱼藤酮共同孵育PC12细胞24h,0.5和1.0μmol/L的姜黄素使细胞活力以及蛋白酶体水解酶活性明显升高、α-突出核蛋白的表达和聚集明显减少、细胞凋亡率明显降低；5.0和10μmol/L姜黄素对鱼藤酮的拮抗作用明显减弱,细胞活力和蛋白酶体水解酶活性、以及细胞凋亡率与鱼藤酮组比较均无明显差异。
结论：低浓度姜黄素能够通过诱导PC12细胞蛋白酶体水解酶活性、抑制α-突出核蛋白的表达和聚集,从而拮抗鱼藤酮诱导的PC12细胞的损伤。
目的：探讨姜黄素(curcumin,Cur)通过诱导热休克蛋白(Hsp70)高表达、抑制α-突触核蛋白的异常表达和聚集、促进蛋白酶体系统降解异常α-突触核蛋白(a-synuclein)对多巴胺能细胞的保护作用
方法：选用大鼠嗜铬细胞瘤株PC12细胞,利用鱼藤酮诱导其损伤建立帕金森病细胞模型,利用姜黄素进行干预；采用MTT法检测细胞活力、荧光酶标仪检测蛋白酶体水解酶活性、Western blotting法检测Hsp70和α-突出核蛋白的表达、免疫荧光法检测细胞内Hsp70的表达和α-突出核蛋白的聚集。
结果：鱼藤酮组PC12细胞活力及蛋白酶体水解酶活性明显降低,Hsp70的表达轻度增加、α-突出核蛋白表达和聚集明显增加；经不同浓度姜黄素预处理4h后与0.1μmol/L鱼藤酮共同孵育PC12细胞24h,与鱼藤酮组比较,0.5μmol/L和1.0μmol/L的姜黄素使细胞活力以及蛋白酶体水解酶活性明显升高、Hsp70表达明显升高,α-突出核蛋白的表达和聚集明显减少；5.0μmol/L和10μmol/L姜黄素对鱼藤酮的拮抗作用明显减弱,细胞活力与鱼藤酮组比较均无明显差异(P<0.05),胰蛋白酶、多肽-谷氨酰多肽水解酶活性与鱼藤酮组比较均无明显差异(P<0.05)、10μmol/L姜黄素组糜蛋白酶样水解酶活性进一步降低,与鱼藤酮组比较有极显著性差异(P<0.01)。
结论：低浓度姜黄素能够通过诱导PC12细胞表达Hsp70、诱导蛋白酶体水解酶活性、进而抑制α-突出核蛋白的表达和聚集,从而拮抗鱼藤酮诱导的PC12细胞的损伤。
目的：探讨小胶质细胞在多巴胺能细胞损伤中的作用,以及姜黄素通过抑制小胶质细胞反应保护多巴胺能细胞的机制。
方法：选用大鼠嗜铬细胞瘤株PC12细胞,利用鱼藤酮诱导其损伤建立帕金森病细胞模型,用姜黄素预处理4h的BV-2细胞再经鱼藤酮处理4h后的细胞上清作为条件培养液(Microglia conditioned medium with Curcumin,MCMC),处理PC12细胞,并设空白对照组。应用四甲基偶氮唑盐法(MTT法)检测细胞活力；DCFH-DA染色检测BV-2细胞内活性氧类物质(ROS)水平；磷脂结合蛋白(Annexin V)-碘化丙啶(PI)双染色流式细胞仪检测PC12细胞凋亡。Western blotting法检测NADPH氧化酶P47-phox亚基蛋白在BV-2细胞膜上的表达。
结果：与对照组组相比,姜黄素预处理的BV-2细胞,其ROS水平降低(P<0.01)；受MCMC处理的PC12细胞,细胞活力增加,细胞凋亡率降低(P<0.01)。而单独用5nM鱼藤酮作用于PC12细胞,其存活率及凋亡率与空白组相比无明显差别(P>0.05)。鱼藤酮诱导BV-2细胞激活后,结合与BV-2细胞膜的NADPH氧化酶P47-phox亚基蛋白明显增加(P<0.01),姜黄素预处理使结合与BV-2细胞膜的NADPH氧化酶P47-phox亚基蛋白明显降低(P<0.05)。
结论：鱼藤酮激活小胶质细胞NADPH氧化酶产生ROS,损伤多巴胺能细胞。姜黄素通过抑制小角质细胞内NADPH氧化酶的激活,减少ROS的产生,从而保护多巴胺能细胞。
Abstract objective to investigate the cytoprotection of curcumin against rotenone-induced injury and the molecular mechanisms underlying in PC12 cells.
Methods:the insulted mode of PC 12 Cells was established with rotenone (Ro),cell viability was determined using MTT reduction assay;the content of reactive oxygen species(ROS) was detected with the method of DCFH-DA staining,chromatometry to detect the total activity of SOD;DCFH-DA staining to measure the level of intracellular ROS;flow cytometric analysis to survey the rate of cell apoptosis
Results:0.1μmol/L-1.0μmol/L Curcumin significantly decreased the inhibitory rate of Rotenone on the growth of PC 12 cells for 24h; 0.1μmol/L-1.0μmol/L Curcumin significantly ameliorate the changes in the morphology of PC 12 cells;increased the activities of intracellular SOD;decreased the production of intracellular ROS and inhibited the apoptosis of PC 12 cells induced by Rotenone for 24h.
Conclusion:Curcumin can resist rotenone-induced cytotoxicity probably by the mechanism of scavenging intracellular ROS and increasing the activity of antioxidase.
Purpose to investigate the effect of Curcumin on aggregtion of alph-synuclein and its mechanism to resist the Rotenone-induced injury to PC 12 cells.
Methods the cellular mode of parkinson's disease was established by adoption of rat pheochromocytoma strain PC12 cells and utilization of Rotenone to induce injury to them;Cell viability was assessed with MTT,Enzymatic activity of three hydrolases in proteasome was measured by detection of the fluorophore of various cleavaged synthetic fluorogenic peptides;The expression and aggregation of a-synuclein in PC12 cells was observed by Western blot and immunofluorescence respectively and cell apoptosis by flow cytometry.
Results Cell viability and activity of proteasome of Rotenone group were decreased dramatically;The expression and aggregation of a-synuclein and cell apotosis of Rotenone group increased apparently.0.5μmol/L and 1.0μmol/L Curcumin allowed Cell viability and activity of proteasome of PC 12 cells to increase significantly after co-incubation of Curcumin-pretreated PC12 cells with Ro for 24h and the resistant role of 5.0μmol/L and 10μmol/L Curcumin on the injury of Ro-induced PC12 cells decreased apparantly.
Conclusion low concentrion of Curcumin was able to induce the activity of proteasome and inhibit the expression and aggregation of a-synuclein in PC12 cells and thereby to alleviate the injury of Rotenone-induced PC 12 cells.
Abstract:To explore the protective effects of curcumin on dopaminergic cells by inducing the expression of heat shock protein70(Hsp70), inhibiting anormal expression and aggregation of a-synuclein and promoting proteasome system to degrade abnomal a-synuclein.
Methods:The cellular model for overexpressing a-synuclein was established by adoption of rat pheochromocytoma strain PC 12 cells treated with Rotenone.Cell viability was assessed with MTT,Enzymatic activity of three hydrolases in proteasome was measured by detection of the fluorophore of various cleavaged synthetic fluorogenic peptides;Western blot was used to dectect the expression of Hsp70 and a-synuclein;immunofluorescence to observe their expression andα-synuclein aggregation.
Results:At Rotenone group,cell viability、activity of proteasome were decreased dramatically(P<0.01),the expression level of Hsp70 and a-synuclein were increased significantly(P<0.01).Pretreatment with 0.5μmol/L and 1.0μmol/L Curcumin allowed cell viability,activity of proteasome in PC12 cells to increase significantly after co-incubation with Rotenone for 24h campared with Rotenone group(P<0.01),the expression level of Hsp70 to incease significantly(P<0.05,P<0.01 respectively),and significantly reduce a-synuclein expression (P<0.05) and aggregation;The protection of 5.0μmol/L and 10μmol/L Curcumin against the injury of Ro-induced PC12 cells decreased apparantly. Cell viability, activity of three hydrolases in proteasome are not significantly different from those of Rotenone group (P>0.05).
Conclusion low concentrion of Curcumin was able to induce higher expression of Hsp70 and the activity of proteasome and therefore inhibit the anormal expression and aggregation of a-synuclein in PC 12 cells and thereby to alleviate the injury of Rotenone-induced PC 12 cells.
Objective:To explore the effects of microglia on the impairment of dopaminergic cells and the mechanisms of Curcumin's protective effects on them by inhibitting microglia activation.
Methods:The cellular model of PD was established by adoption of rat pheochromocytoma strain PC12 cells treated with Rotenone,PC12 cells were treated with the medium from Curcumin-pretreated-BV-2 cells which were conditioned with Rotenone,and the blank control group was established.Cell viability was assessed with MTT;DCFH-DA staining was used to measure the level of intracellular ROS in BV-2 cells;flow cytometric analysis to survey the rate of cell apoptosis;Western blot was used to dectect the level of NADPH oxidase combining with membrane of BV-2 cell.
Results:Compared with the control group,the level of ROS in Curcumin-pretreated-BV-2 cells groups was decreased(P<0.01);Cell viability of PC 12 cells treated with MCMC was increased and the rate of apoptosis of them was decreased(P<0.01).The cell viability and rate of apoptosis of PC12 cells treated only with 5nM Rotenone were not different with those of blank control group(P>0.05).The level of NADPH oxidase P47-phox-combined with BV-2 cellular membrane of BV-2 activated by Rotenone was increased significantly(P <0.01),and the pretreatment of BV-2 cells with Curcumin made the level of NADPH oxidase P47-phox-combined with BV-2 cellular membrane decline significantly(P< 0.05)
Results:Microglia in which NADPH oxidase was activated by Rotenone impair dopaminergic cells by producing ROS.Curcumin protects dopaminergic cells by inhibitting activation of NADPH oxidase in microglia and decreasing the production of ROS.
引文
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