The voltage-dependent anion channel （VDAC） plays an essential role in the permeability of mltochondrial membrane. In the present study, we isolated a novel VDAC gene （brvdac） based on the assembly of expressed seq...The voltage-dependent anion channel （VDAC） plays an essential role in the permeability of mltochondrial membrane. In the present study, we isolated a novel VDAC gene （brvdac） based on the assembly of expressed sequence tag sequences from Brassica rapa L. and explored its differential expression patterns In growth, tissues, abiotlc stress, and stress recovery. Results of a tissue-specific expression study in young seedlings Indicated that, of all tissues tested, brvdac expression was the highest in the leaves. Under cold, drought, and salt stresses, brvdac expression showed a transient Increase, and then returned to normal levels when the stress was removed. When plants were exposed to heat shock, there was no Increase in brvdac expression, whereas during recovery a quick and considerable increase in expression was observed. These observations indicate that dissimilar modulations of brvdactranscription may occur when plant cells encounter heat shock and the other three types of stress. In addition, phylogenetic analysis Implied that an earlier duplication of vdac probably occurred before the divergence between monocotyledons and dicotyledons.展开更多
Voltage-dependent anion channel 1（VDAC1） is thought to contribute to the progression of tumor development. However, whether VDAC1 contributes to bone cancer pain remains unknown. In this study, we found that the exp...Voltage-dependent anion channel 1（VDAC1） is thought to contribute to the progression of tumor development. However, whether VDAC1 contributes to bone cancer pain remains unknown. In this study, we found that the expression of VDAC1 was upregulated in the L2–5 segments of the spinal dorsal horn at 2 and 3 weeks after injection of tumor cells into the tibial cavity. Intrathecal injection of a VDAC1 inhibitor significantly reversed the pain hypersensitivity and reduced the over-expression of Toll-like receptor 4（TLR4）. Intrathecal injection of minocycline, an inhibitor of microglia, also attenuated the pain hypersensitivity of rat models of bone cancer pain.These results suggest that VDAC1 plays a significant role in the development of complicated cancer pain, possibly by regulating the expression of TLR4.展开更多
目的:探讨1,4,5-三磷酸肌醇1型受体(inositol 1,4,5-trisphosphate receptor type 1,IP3R1)调控钙/钙调蛋白依赖性蛋白激酶Ⅱ(calcium/calmodulin-dependent protein kinaseⅡ,CaMKⅡ)和电压依赖性阴离子通道1(voltage-dependent anion ...目的:探讨1,4,5-三磷酸肌醇1型受体(inositol 1,4,5-trisphosphate receptor type 1,IP3R1)调控钙/钙调蛋白依赖性蛋白激酶Ⅱ(calcium/calmodulin-dependent protein kinaseⅡ,CaMKⅡ)和电压依赖性阴离子通道1(voltage-dependent anion channel 1,VDAC1)在海洛因(heroin,HE)致心肌细胞节律异常中的作用。方法:联合蛋白组学和GEO(Gene Expression Omnibus)数据库分析心律失常芯片数据,寻找关键调控因子。构建IP3R1基因敲减慢病毒并感染原代乳大鼠心肌细胞(neonatal rat cardiomyocytes,NRCMs),实验分为对照(control)组、HE组和HE+shIP3R1组。结晶紫染色观察心肌细胞形态;ELISA法检测乳酸脱氢酶(lactate dehydrogenase,LDH)和天冬氨酸转氨酶(aspartate aminotransferase,AST)水平;透射电镜观察线粒体形态学变化;Fluo-4/AM探针法检测细胞内Ca^(2+)浓度;DCFH-DA荧光探针检测细胞内活性氧(reactive oxygen species,ROS)含量;JC-1染色法检测线粒体膜电位(mitochondrial membrane potential,MMP)水平;ATP检测试剂盒检测细胞内ATP水平;免疫共沉淀(co-immunopre-cipitation,Co-IP)分析IP3R1与CaMKⅡδ和VDAC1蛋白之间的相互作用;Western blot检测IP3R1、CaMKⅡδ、p-CaM-KⅡδ(T287)和VDAC1的蛋白水平。结果:结合蛋白质组学和基因表达谱数据集GSE89410分析,筛选得到80个差异共表达分子,基于基因本体论(Gene Ontology,GO)功能注释和京都基因与基因组百科全书(Kyoto Encyclopedia of Genes and Genomes,KEGG)富集分析结果,最终筛选出关键因子IP3R1,且通过STRING数据库获得IP3R1结合蛋白:CaMKⅡδ和VDAC1。Co-IP结果验证IP3R1与CaMKⅡδ和VDAC1存在相互作用,且HE干预后NRCMs中IP3R1与CaMKⅡδ和VDAC1之间的相互作用增强。体外细胞实验显示,与control组相比,HE组NRCMs数量急剧减少,细胞膜变窄,伪足减少,细胞核结构模糊;LDH和AST水平均显著上升(P<0.05);线粒体超微结构损伤严重,证实HE对NRCMs具有毒性作用并导致线粒体损伤。与control组相比,HE组心肌细胞内Ca^(2+)浓度、ROS水平、MMP以及IP3R1、p-CaMKⅡδ(T287)和VDAC1蛋白水平均显著升高(P<0.05),而HE+shIP3R1组这些指标均显著减低(P<0.05);ATP水平则相反。这证实沉默IP3R1表达可减轻HE干预后NRCMs的钙超载及线粒体损伤。结论:IP3R1通过调控CaMKⅡ和VDAC1引起心肌细胞钙超载和ROS生成增多,参与HE诱导的心肌细胞节律异常。展开更多
文摘The voltage-dependent anion channel （VDAC） plays an essential role in the permeability of mltochondrial membrane. In the present study, we isolated a novel VDAC gene （brvdac） based on the assembly of expressed sequence tag sequences from Brassica rapa L. and explored its differential expression patterns In growth, tissues, abiotlc stress, and stress recovery. Results of a tissue-specific expression study in young seedlings Indicated that, of all tissues tested, brvdac expression was the highest in the leaves. Under cold, drought, and salt stresses, brvdac expression showed a transient Increase, and then returned to normal levels when the stress was removed. When plants were exposed to heat shock, there was no Increase in brvdac expression, whereas during recovery a quick and considerable increase in expression was observed. These observations indicate that dissimilar modulations of brvdactranscription may occur when plant cells encounter heat shock and the other three types of stress. In addition, phylogenetic analysis Implied that an earlier duplication of vdac probably occurred before the divergence between monocotyledons and dicotyledons.
基金supported by grants from the National Key Research and Development Program of China (2016YFC1302200)the National Natural Science Foundation of China (31730040, 81070884, and 81471137)+2 种基金the Suzhou Health Planning Commission’s Key Clinical Diagnosis and Treatment Program (LCZX201606)the Priority Academic Program Development of Jiangsu Higher Education Institutions of Chinasubject to the Preponderant Clinic Discipline Group Project funding from the Second Affiliated Hospital of Soochow University (XKQ2015008)
文摘Voltage-dependent anion channel 1（VDAC1） is thought to contribute to the progression of tumor development. However, whether VDAC1 contributes to bone cancer pain remains unknown. In this study, we found that the expression of VDAC1 was upregulated in the L2–5 segments of the spinal dorsal horn at 2 and 3 weeks after injection of tumor cells into the tibial cavity. Intrathecal injection of a VDAC1 inhibitor significantly reversed the pain hypersensitivity and reduced the over-expression of Toll-like receptor 4（TLR4）. Intrathecal injection of minocycline, an inhibitor of microglia, also attenuated the pain hypersensitivity of rat models of bone cancer pain.These results suggest that VDAC1 plays a significant role in the development of complicated cancer pain, possibly by regulating the expression of TLR4.
