6-OHDA损伤神经细胞CXCR4/CXCL12表达变化的实验研究
收稿日期: 2013-12-16
网络出版日期: 2014-12-04
基金资助
国家自然科学基金（81371471，81071081）； 教育部博士点基金（20120131120049）； 山东省自然基金（ZR2012HQ018， ZR2010HM051）； 山东省科技发展计划（2011GSF11810）； 山东大学自主创新基金(2012TS113)，山东省卫生厅基金（2013WS0008）
The change of PC12 cells and the expression of CXCR4/CXCL12 under the 6-OHDA’s injury
Received date: 2013-12-16
Online published: 2014-12-04
目的 研究6-OHDA损伤PC12细胞CXCR4/12表达的变化。 方法 以梯度浓度的6-OHDA 处理PC12细胞，光镜观察各组PC12细胞的形态学变化；MTT法检测6-OHDA对PC12细胞的损伤；间接免疫荧光染色法检测6-OHDA不同浓度下PC12细胞CXCR4/CXCL12表达的变化。 结果 随6-OHDA浓度的增加，PC12细胞的存活率呈梯度降低；光镜下观察发现PC12细胞数减少，轴突变短甚至消失；间接免疫荧光染色则显示CXCL12及其受体CXCR4在神经细胞的表达增加。 结论 6-OHDA浓度的增加可导致PC12细胞凋亡，同时伴有CXCL12及其受体CXCR4表达增加。
关键词： 6-OHDA; CXCR4/CXCL12; PC12细胞; 形态学变化; 间接免疫荧光染色
王辉 , 暴丽华 , 李涛 , 李贵宝 , 吴琦 , 朱德晓 , 吴金涛 , 刘海莉 , 张静 , 孙晋浩 . 6-OHDA损伤神经细胞CXCR4/CXCL12表达变化的实验研究[J]. 中国临床解剖学杂志, 2014 , 32(6) : 680 -684 . DOI: 10.13418/j.issn.1001-165x.2014
Objective To study the change of PC12 cells and the expression of CXCR4 and CXCL12 under the 6-OHDA’s injury. Methods PC12 cells were treated with concentration gradient of 6-OHDA.The the morphological change of PC12 cells was observed with light microscope, then MTT assay was used to detect the viability of PC12 cells treated with 6-OHDA . And the expression of CXCL12 and CXCR4 was detected in different 6-OHDA concentrations with indirect immunofluorescence technique. Results With the increase of the concentration of 6-OHDA, the survival rate of PC12 cells decreased gradually. The number of the PC12 cells decreased, with the axon becoming shorter or disappearing. The results of indirect immunofluorescence technique showed that the expression of CXCR4 and CXCL12 increased with the amount of 6-OHDA. Conclusion The increase of the concentration of 6-OHDA leads to the apoptosis of the PC12 cells and the increase of the expression of CXCR4 and CXCL12.
[1] Lunn JS, Sakowski SA, Hur J, et al. Stem cell technology for neurodegenerative diseases
[J]. Ann Neurol, 2011, 70(3): 353-361.
[2] Soykan I, Lin Z, Bennett JP, et al. Gastric myoelectrical activity in patients with Parkinson's disease (Evidence of a Primary Gastric Abnormality)
[J]. Dig Dis Sci, 1999, 44(5): 927-931.
[3] Cersosimo MG, Benarroch EE. Pathological correlates of gastrointes- tinal dysfunction in Parkinson's disease
[J]. Neurobiol Dis, 2012, 46(3): 559-564.
[4] Pfeiffer RF. Gastrointestinal dysfunction in Parkinson's disease
[J]. Parkinsonism Relat Disord, 2011,17(1): 10-15.
[5] Salawu FK, Danburam A, Olokoba AB. Non-motor symptoms of Parkinson's disease: diagnosis and management
[J]. Niger J Med, 2010, 19(2):126-131.
[6] Takahashi M. Role of the SDF-1/CXCR4 system in myocardial infarction
[J]. Circ J, 2010, 74(3): 418-423.
[7] Gazitt Y. Homing and mobilization of hematopoietic stem cells and hematopoietic cancer cells are mirror image processes, utilizing similar signaling pathways and occurring concurrently: circulating cancer cells constitute an ideal target for concurrent treatment with chemotherapy and antilineage-speci?c antibodies
[J]. Leukemia, 2004, 18(1): 1-10.
[8] ernández-López C, Varas A, Sacedón R, et al. The CXCL12/CXCR4 pair in aged human thymus
[J]. Neuroimmunomodulation, 2010,17(3): 217-220.
[9] Gassmann P, Haier J, Schlüter K, et al. CXCR4 regulates tumor cell extravasation in vivo
[J]. Neoplasia, 2009, 11(7): 651-661.
[10]Shimoji M, Pagan F, Healton EB, et al. CXCR4 and CXCL12 expression is increased in the nigro-striatal system of Parkinson's disease
[J]. Neurotox Res, 2009,16(3): 318-328.
[11]Zeevalk GD, Razmpour R, Bernard LP. Glutathione and Parkinson's disease: is this the elephant in the room
[J]? Biomed Pharmacother, 2008, 62(4):236-249.
[12]Jenner P. Oxidative stress and Parkinson's disease
[J]. Handb Clin Neurol, 2007, 83:507-520.
[13]Cuadrado A, Rojo A I. Heme oxygenase-1 as a therapeutic target in neurodegenerative diseases and brain infections
[J]. Curr Pharm Des, 2008, 14(5):429-442.
[14]Chao Y, Wong SC, Tan EK. Evidence of inflammatory system involvement in Parkinson's disease
[J]. Biomed Res Int, 2014:308654.
[15]Gerhard A, Pavese N, Hotton G, et al. In vivo imaging of microglial activation with
[11C](R)-PK11195 PET in idiopathic Parkinson's disease
[J]. Neurobiol Dis, 2006, 21(2):404-412.
[16]Tran PB, Ren D, Veldhouse TJ, et al. Chemokine receptors are expressed widely by embryonic and adult neural progenitor cells
[J]. J Neurosci Res, 2004, 76(1): 20-34.
[17]Carbajal KS, Schaumburg C, Strieter R, et al. Migration of engrafted neural stem cells is mediated by CXCL12 signaling through CXCR4 in a viral model of multiple sclerosis
[J]. Proc Nati Acad Sci U S A, 2010, 107(24): 11068-11073.
[18]McCandless EE, Budde M, Lees JR, et al. IL-1R signaling within the central nervous system regulates CXCL12 expression at the blood-brain barrier and disease severity during experimental autoimmune encephalomyelitis
[J]. J Immunol, 2009, 183(1):613-620.
[19]McCandless EE, Piccio L, Woerner BM, et al. Pathological expression of CXCL12 at the blood -brain barrier correlates with severity of multiple sclerosis
[J]. Am J Pathol , 2008, 172(3):799-808.
[20]Mocchetti I, Bachis A, Masliah E. Chemokine receptors and neurotrophic factors: potential therapy against aids dementia
[J]? J Neurosci Res, 2008, 86(2):243-255.
[21]Robin AM, Zhang ZG, Wang L, et al. Stromal cell derived factor-1 alpha mediates neural progenitor cell motility after focal cerebral ischemia
[J] . J Cereb BloodFlow Metab, 2006, 26(1):125- 134.
[22]Bachis A, Mocchetti I. The chemokine receptor CXCR4 and not the N-methyl-D-aspartate receptor mediates gp120 neurotoxicity in cerebellar granule cells
[J]. J Neurosci Res, 2004, 75(1):75-82.
[23]Corasaniti MT , Piccirilli S, Pao letti A, et al. Evidence that the HIV-1 coat protein gp120 causes neuronal apoptosis in the neocortex of rat via a mechanism involving CXCR4 chemokine receptor
[J]. Neurosci Lett, 2001, 312(2): 67- 70.
/
| 〈 |
|
〉 |
京ICP备08002354号-3
