期刊文献+

Cdk5在肾小球足细胞中的表达及作用 被引量:3

Expression and function of Cdk5 in glomerular podocyte
下载PDF
导出
摘要 目的研究周期素依赖性蛋白激酶-5(Cdk5)及其激活剂p35在肾小球足细胞中的表达及作用。方法分别培养原代小鼠神经细胞、原代小鼠分化成熟的离体足细胞(简称足细胞)以及人胚肾细胞(HEK293细胞),应用免疫印迹、免疫沉淀及同位素标记等方法检测Cdk5、p35的表达及Cdk5的活性;以原代小鼠分化成熟的离体足细胞为研究对象,分为正常组、ROS组(Cdk5活性抑制组)、Cdk5 siRNA组(Cdk5表达沉默组),观察Cdk5的表达及活性,并应用Cdk5 siRNA、Cdk5化学抑制剂-Roscovitine进行抑制实验。结果离体培养原代小鼠分化成熟的足细胞中均有Cdk5及p35蛋白的表达;Cdk5在足细胞中具有活性;沉默Cdk5表达、应用Cdk5活性抑制剂Roscovitine抑制Cdk5活性后,可引起足细胞特异性标志物WT1的表达减少,说明足细胞受到损伤,数量减少。结论 Cdk5的表达及活性在维持正常足细胞功能中起重要作用。 Objective To study the expression and function of Cdk5 and its activator p35 in glomerular podocyte. Methods Primary culture of cortical neurons,podocyte,and HEK293 cells of mouse in in vitro,and the expression of Cdk5 were detected,p35 was detected by u- sing western blot and immunofluorescence staining,and the activity of Cdk5 using immune precipitation and isotope labeling. Results There were proteins p35 and Cdk5 expressed in the podocyte of mouse primarily cultured in vivo; p35 could active Cdk5 ; silencing the expression of Cdk5 or inhibition of Cdk5 activity using roscovitine (a Cdk5 inhibitor) could reduce the expression of WT1 ,a specific marker in podocyte, which indicates the podocyte damage and cell decreases. Conclusion The expression and activity of Cdk5 play an important role in maintai- ning normal functions in podosyte.
出处 《宁夏医学杂志》 CAS 2014年第3期193-195,I0001,共4页 Ningxia Medical Journal
基金 国家自然科学基金资助项目(NSFC81060066) 宁夏自然科学基金资助项目(NZ10162) 宁夏科技攻关资助项目(KGX1910-16) 宁夏科技攻关国际合作项目(2011ZYH169)
关键词 周期素依赖性蛋白激酶-5 P35 足细胞 SIRNA Cdk5活性 Cdk5 p35 Sertoli cell Sirna Cdk5 activity
  • 相关文献

参考文献9

  • 1Kom SH, Ryan TA. CDK5 serves as a major control point in neuro-transmitter release [ J ]. Neuron,2010,67 ( 5 ) :797 - 809.
  • 2Manser C, Vagnoni A, Guillot F. CdkS/p35 phosphorylates lemur tyrosine kinase - 2 to regulate protein phosphatase - 1C phosphoryl- ation and activity[ J ]. J Neurochem ,2012,121 ( 3 ) :343 - 348.
  • 3Wei FY. Cdk5 - dependent regulation of glucose - stimulated insu- lin secretion [ J ]. Nat Med,2005,11 ( 10 ) : 1104.
  • 4Caroline B, Marshall, Stuart J, et al. Cell cycle regulatory proteins in podocyte health and disease [ J ]. Nephron Exp Nephology, 2007, 106:51 -59.
  • 5Zheng YL. A Cdk5 inhibitory peptide reduces tau hyperphosphory- lation and apoptosis in neurons[J]. Embo J,2005,24( 1 ) :209.
  • 6张红丽,刘亚玲.CDK-5在神经系统变性疾病的研究进展[J].医学综述,2012,18(19):3166-3169. 被引量:4
  • 7Marshall SM. The podocyte : a potential therapeutic target in diabetic nephropathy current [ J ]. Pharmaceutical Design, 2007, 13 : 2713 - 2720.
  • 8Mrowka AL, Schedl A. Wilms' tumor suppressor gene WT1 :from structure to renal pathophysiologic features[ J]. J Am Soc Nephrol, 2000,11(16) :106.
  • 9Migliaccio AR,Bengra C,Ling J,et al,Stable and unstable transgene integration sitesin the human genome:extinction of the Green Fluores- cent Protein transgene in K562 cells[J]. Gene,2000,256:197.

二级参考文献34

  • 1Hellmich MR,Pant HC,Wada E,et al.Neuronal cdc2-like kinase:a cdc2-related protein kinase with predominantly neuronal expres-sion[J].Proc Natl Acad Sci USA,1992,89(22):10867-10871.
  • 2Tang D,Chun AC,Zhang M,et al.Cyclin-dependent Kinase 5(Cdk5)activation domain of neuronal Cdk5 activator.Evidence ofthe existence of cyclin fold in neuronal Cdk5a activator[J].J BiolChem,1997,272(19):12318-12327.
  • 3Dhariwala FA,Rajadhyaksha MS.An unusual member of the Cdkfamily:Cdk5[J].Cell Mol Neurobiol,2008,28(3):351-369.
  • 4Rosales JL,Lee KY.Extraneuronal roles of cyclin-dependent ki-nase 5[J].Bioessays,2006,28(10):1023-1034.
  • 5Asada A,Yamamoto N,Gohda M,et al.Myristoylation of P39 andp35 is a determinant of cytoplasmic or nuclear localization of activecyclin-dependent kinase 5 complexes[J].J Neurochem,2008,106(3):1325-1336.
  • 6Kamei H,Saito T,Ozawa M,et al.Suppression of calpain-depend-ent cleavge of the CDK5 activator p35 to p25 by site-specific phos-phorylation[J].J Biol Chem,2007,282(3):1687-1694.
  • 7Hirasawa M,Ohshima T,Takahashi S,et al.Perinatal abrogation ofCdk5 expression in brain results in neuronal migration defects[J].Proc Natl Acad Sci U S A,2004,101(16):6249-6254.
  • 8Ohshima T,Ward JM,Huh CG,et al.Targeted disruption of thecyclin-dependent kinase 5 gene results in abnormal corticogenesis,neuronal pathology and perinatal death[J].Proc Natl Acad SciUSA,1996,93(20):11173-11178.
  • 9Takahashi S,Ohshima T,Hirasawa M,et al.Conditional deletion ofneuronal cyclin-dependent kinase 5 in developing forebrain resultsin microglial activation and neurodegeneration[J].Am J Pathol,2010,176(1):320-329.
  • 10Gao C,Negash S,Wang HS,et al.Cdk5 mediates changes in mor-phology and promotes apoptosis of astrocytoma cells in response toheat shock[J].J Cell Sci,2001,114(Pt 6):1145-1153.

共引文献3

同被引文献17

  • 1Brinkkoetter PT, Wu JS,Ohse T,et al. p35 the non - cyclin activa-tor of Cdk5 protects podocytes against apoptosis in vitro and in vivo[J]. Kidney International,2010,77(8) :690 -699.
  • 2Tufro A,Veron D. VEGF and podocytes in diabetic nephropathy[J]. Semin Nephrol,2012,32(4) :385 -393.
  • 3White KE, Bilous RW, Diabiopsies Study Group. Structural altera-tions to the podocyte are realated to proteinuria in type 2 diabeticpatients[ J] . Nephrol Dial Transplant,2004,19 (6) :1437 - 1440.
  • 4Rosales JL,Lee KY. Extraneuronal roles of cyclin - dependent ki-nase 5[ J]. Bioessays,2006,28( 10) : 1023 - 1034.
  • 5Zhang Y,U H,Hao J,et al. High glucose increases Cdk5 activity inpodocytes via transforming growth factor - pi signaling pathway[J]. Exp Cell Res,2014,326(2) :219 -229.
  • 6Taniguchi YI,Pippin JW,Hagmann H,et al. Both cyclin I and p35are required for maximal survival benefit of cyclin - dependent ki-nase 5 in kidney podocytes [ J ]. Am J Physiol Renal Physiol ,2012,302(9) :1161 -1171.
  • 7Advani A. Vascular endothelial growth factor and the kidney :some-thing of the marvelous [ J ]. Curr Opin Nephrol Hypertens, 2014,23(1):87 -92.
  • 8Cha DR,Kang YS,Han SY,et al. Vascular endothelial growth fac-tor is increased during early stage of diabetic nephropathy in typeII diabetic rats[ J] . J Endocrinol,2004,183(1) : 183 - 194.
  • 9Hohenstein B,Hausknecht B,Boehmer K,et al. Local VEGF activ-ity but not VEGF expression is tightly regulated during diabeticnephropathy in man[ J] . Kidney Int,2006,69 : 1654 - 1661.
  • 10Chen S,Kasama Y,Lee JS,et al. Podocyte - derived vascular en-dothelial growth factor mediates the stimulation of alpha 3 (IV)collagen production by transforming growth factor - beta 1 inmouse podocytes[ J]. Diabetes,2004,53(11) :2939 —2949.

引证文献3

二级引证文献3

相关作者

内容加载中请稍等...

相关机构

内容加载中请稍等...

相关主题

内容加载中请稍等...

浏览历史

内容加载中请稍等...
;
使用帮助 返回顶部