目的探讨MIB1、RPS6KA1基因甲基化表达状态通过ERK信号通路对激素抵抗型哮喘的影响;方法病例组为确诊激素抵抗型哮喘者20例,病例对照组为确诊支气管哮喘并明确得到有效控制者20例,正常对照组为健康体检者20例,利用Sequenom Mass ARRAY...目的探讨MIB1、RPS6KA1基因甲基化表达状态通过ERK信号通路对激素抵抗型哮喘的影响;方法病例组为确诊激素抵抗型哮喘者20例,病例对照组为确诊支气管哮喘并明确得到有效控制者20例,正常对照组为健康体检者20例,利用Sequenom Mass ARRAY方法检测基因甲基化表达状态,用SPSS22.0统计软件进行分析;结果本研究共检测RPS6KA1有4个CpG位点、MIB1基因有3个CpG位点,其中RPS6KA1基因低表达,其中CpG1,CpG2,CpG3在病例组与病例对照组、正常对照组间比较差异有统计学意义(P <0.05),而MIB1基因甲基化表达水平在三组比较差异均无统计学意义(P>0.05)。结论 RPS6KA1基因低表达可能通过影响ERK信号通路而在SRA中起作用。展开更多
核糖体蛋白S6激酶A3(ribosomal protein S6 kinase A3,RPS6KA3)具有丝氨酸/苏氨酸激酶活性,在机体的生理过程中发挥重要作用。为了研究RPS6KA3基因的性质和功能,利用一系列生物信息学分析软件对该基因序列及其编码蛋白的结构和特性进行...核糖体蛋白S6激酶A3(ribosomal protein S6 kinase A3,RPS6KA3)具有丝氨酸/苏氨酸激酶活性,在机体的生理过程中发挥重要作用。为了研究RPS6KA3基因的性质和功能,利用一系列生物信息学分析软件对该基因序列及其编码蛋白的结构和特性进行生物信息学分析。结果表明,人RPS6KA3基因共编码740个氨基酸组成的多肽,其在进化过程中高度保守,隶属于PKc_like超家族,是一种等电点为6.41的不稳定的水溶性蛋白,无信号肽序列和跨膜结构。该蛋白定位于细胞质的可能性最大,主要的二级结构为α-螺旋结构,具有多个磷酸化功能位点。与RPS6KA3相互作用的蛋白主要是MAPK信号途径相关蛋白、mTOR信号途径相关蛋白及蛋白合成相关蛋白等。分析结果为进一步研究RPS6KA3在生命过程中的作用提供重要信息。展开更多
During spermatogenesis, developi ng germ cells that lack the cellular ultrastructures of filopodia and lamellipodia gen erally found in migrating cells, such as macrophages and fibroblasts, rely on Sertoli cells to su...During spermatogenesis, developi ng germ cells that lack the cellular ultrastructures of filopodia and lamellipodia gen erally found in migrating cells, such as macrophages and fibroblasts, rely on Sertoli cells to support their transport across the seminiferous epithelium. These in elude the transport of preleptote ne spermatocytes across the blood-testis barrier (BTB), but also the transport of germ cells, in particular developing haploid spermatids, across the seminiferous epithelium, that is to and away from the tubule lumen, depending on the stages of the epithelial cycle. On the other hand, cell junctions at the Sertoli cell-cell and Sertoli-germ cell in terface also un dergo rapid remodeli ng, invo Iving disassembly and reassembly of cell j un ctions, which, in turn, are supported by actin- and microtubule-based cytoskeletal remodeling. Interestingly, the underlying mechanism(s) and the invoIving biomolecule(s) that regulate or support cytoskeletal remodeling remain largely unknown. Herein, we used an in vitro model of primary Sertoli cell cultures that mimicked the Sertoli BTB in vivo overexpressed with the ribosomal protei n S6 (rpS6, the down stream signali ng protein of mammalian target of rapamycin complex 1 [mTORCl]) cloned into the mammalian expression vector pCI-neo, namely, quadruple phosphomimetic and constitutively active mutant of rpS6 (pCI-neo/p-rpS6-MT) versus pCI-neo/rpS6-WT (wild-type) and empty vector (pCI-neo/Ctrl) for studies. These findings provide compelling evidence that the mT0RCl/rpS6 signal pathway exerted its effects to promote Sertoli cell BTB remodeling. This was mediated through changes in the organization of actin- and microtubulebased cytoskeletons, involving changes in the distribution and/or spatial expression of actin- and microtubule-regulatory proteins.展开更多
文摘目的探讨MIB1、RPS6KA1基因甲基化表达状态通过ERK信号通路对激素抵抗型哮喘的影响;方法病例组为确诊激素抵抗型哮喘者20例,病例对照组为确诊支气管哮喘并明确得到有效控制者20例,正常对照组为健康体检者20例,利用Sequenom Mass ARRAY方法检测基因甲基化表达状态,用SPSS22.0统计软件进行分析;结果本研究共检测RPS6KA1有4个CpG位点、MIB1基因有3个CpG位点,其中RPS6KA1基因低表达,其中CpG1,CpG2,CpG3在病例组与病例对照组、正常对照组间比较差异有统计学意义(P <0.05),而MIB1基因甲基化表达水平在三组比较差异均无统计学意义(P>0.05)。结论 RPS6KA1基因低表达可能通过影响ERK信号通路而在SRA中起作用。
文摘核糖体蛋白S6激酶A3(ribosomal protein S6 kinase A3,RPS6KA3)具有丝氨酸/苏氨酸激酶活性,在机体的生理过程中发挥重要作用。为了研究RPS6KA3基因的性质和功能,利用一系列生物信息学分析软件对该基因序列及其编码蛋白的结构和特性进行生物信息学分析。结果表明,人RPS6KA3基因共编码740个氨基酸组成的多肽,其在进化过程中高度保守,隶属于PKc_like超家族,是一种等电点为6.41的不稳定的水溶性蛋白,无信号肽序列和跨膜结构。该蛋白定位于细胞质的可能性最大,主要的二级结构为α-螺旋结构,具有多个磷酸化功能位点。与RPS6KA3相互作用的蛋白主要是MAPK信号途径相关蛋白、mTOR信号途径相关蛋白及蛋白合成相关蛋白等。分析结果为进一步研究RPS6KA3在生命过程中的作用提供重要信息。
基金grants from the National Institutes of Health (R01 HD056034 to CYC)the Natural Science Foundation of China (NSFC)(No. 81601264 to LXLand No. 81730042 to RSG).
文摘During spermatogenesis, developi ng germ cells that lack the cellular ultrastructures of filopodia and lamellipodia gen erally found in migrating cells, such as macrophages and fibroblasts, rely on Sertoli cells to support their transport across the seminiferous epithelium. These in elude the transport of preleptote ne spermatocytes across the blood-testis barrier (BTB), but also the transport of germ cells, in particular developing haploid spermatids, across the seminiferous epithelium, that is to and away from the tubule lumen, depending on the stages of the epithelial cycle. On the other hand, cell junctions at the Sertoli cell-cell and Sertoli-germ cell in terface also un dergo rapid remodeli ng, invo Iving disassembly and reassembly of cell j un ctions, which, in turn, are supported by actin- and microtubule-based cytoskeletal remodeling. Interestingly, the underlying mechanism(s) and the invoIving biomolecule(s) that regulate or support cytoskeletal remodeling remain largely unknown. Herein, we used an in vitro model of primary Sertoli cell cultures that mimicked the Sertoli BTB in vivo overexpressed with the ribosomal protei n S6 (rpS6, the down stream signali ng protein of mammalian target of rapamycin complex 1 [mTORCl]) cloned into the mammalian expression vector pCI-neo, namely, quadruple phosphomimetic and constitutively active mutant of rpS6 (pCI-neo/p-rpS6-MT) versus pCI-neo/rpS6-WT (wild-type) and empty vector (pCI-neo/Ctrl) for studies. These findings provide compelling evidence that the mT0RCl/rpS6 signal pathway exerted its effects to promote Sertoli cell BTB remodeling. This was mediated through changes in the organization of actin- and microtubulebased cytoskeletons, involving changes in the distribution and/or spatial expression of actin- and microtubule-regulatory proteins.
基金Project supported by the National Natural Science Foundation of China(Nos.31140091 and 31371495)Shandong Natural Science Foundation(No.ZR2013CM040),China
