PGN对BV2细胞内吞Aβ寡聚体的影响

doi:10.3969/j.issn.1006-7795.2011.04.013

首都医科大学学报 ›› 2011, Vol. 32 ›› Issue (4): 501-508.doi: 10.3969/j.issn.1006-7795.2011.04.013

• 神经元退行性变的实验研究 • 上一篇下一篇

PGN对BV2细胞内吞Aβ寡聚体的影响

姜新¹, 相荣才², 白丽娟¹, 张贺敏¹, 陈晓虹¹, 马恩龙³

1. 辽宁省人民医院神经内科,沈阳 110016;2. 中国医科大学基础部生物物理教研室,沈阳 110012;3. 沈阳药科大学药学院药理教研室,沈阳 110016

收稿日期:2011-03-30 修回日期:1900-01-01 出版日期:2011-08-21 发布日期:2011-08-21

Influence of peptidoglycan on BV2 cells after endocytosis of amyloid protein β oligomers

JIANG Xin¹, XIANG Rong-cai², BAI Li-juan¹, ZHANG He-min¹, CHEN Xiao-hong¹, MA En-long³

1. Department of Neurology, The People’s Hospital of Liaoning Province, Shenyang 110016, China;2. Department of Biophysics, College of Basic Medical Sciences, China Medical University, Shenyang 110012, China;3. Department of Pharmacy, School of Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, China

Received:2011-03-30 Revised:1900-01-01 Online:2011-08-21 Published:2011-08-21

摘要/Abstract

摘要： 目的探讨前炎介质肽聚糖(peptidoglycan,PGN)对BV2细胞内吞β淀粉样蛋白_1-42(amyloid protein β,Aβ_1-42)寡聚体的影响及其机制。方法采用细胞株传代法培养BV2细胞,分别替代小胶质细胞;按Klein WL(2002)方法制备Aβ_1-42寡聚体;采用免疫荧光染色鉴定BV2细胞内吞Aβ的量;Western blotting方法检测各组BV2细胞磷酸化p38 丝裂原活化蛋白激酶(phosphorylated p38 mitogen-activated protein kinase,p38MAPK)、p38MAPK蛋白表达情况;PCR方法检测各组BV2细胞鼠同系物甲酰肽受体(mouse homologue formyl peptide receptor 2,mFPR2)mRNA。结果 PGN激活BV2细胞内吞Aβ_1-42寡聚体增多,可被mFPR2拮抗剂抑制;PGN可引起BV2细胞表达mFPR2 mRNA增多,且存在浓度、时间相关性,可被SB202190-p38MAPK抑制剂抑制,且随着SB202190浓度增加,抑制程度增加,各组浓度与0 μmol/L相比,抑制明显差异有统计学意义,1 μmol/L组P<0.05,10、20、30 μmol/L组均P<0.01; PGN作用BV2细胞后各时间点p38MAPK的磷酸化激活程度同对照组相比差异有统计学意义(P<0.01)。结论 PGN可激活BV2细胞内吞Aβ增多,此过程可被mFPR2拮抗剂阻断,推测BV2细胞内吞Aβ可能与mFPR2表达有关;PGN可引起BV2细胞的表达mFPR2 mRNA增多,可能参与激活BV2细胞内吞Aβ的作用;PGN可引起BV2细胞p38MAPK表达量增多,且其抑制剂抑制mFPR2 mRNA表达,可能为激活BV2细胞内吞Aβ的作用机制。

关键词: 肽聚糖, 小胶质细胞, 淀粉样β_1-42蛋白寡聚体, p38 丝裂原活化蛋白激酶, 甲酰肽受体/鼠同系物甲酰肽受体

Abstract: Objective To investigate the influences and mechanisms of the pro-inflammatory medium of peptidoglycan(PGN) on BV2 cells after endocytosis of amyloid protein β(Aβ) oligomers. Methods BV2 cells were cultivated by cell passage method, instead of neurons and microglia separately. Aβ_1-42 oligomers were prepared according to Klein WL (2002). The endocytosis amount of Aβ in BV2 cells was determined by immunofluorescence staining. The expression of phosphorylated p38 mitogen-activated protein kinase(p-p38MAPK), p38MAPK protein of BV2 cells in each group was determined by Western blotting method, and mouse homologue formyl peptide receptor 2(mFPR2)mRNA by PCR method. Results The endocytosis of Aβ42 oligomer increased after BV2 cells was activated by PGN, which could be inhibited by mFPR2. PGN could lead to the increase of mFPR2 mRNA expression in BV2 cells in relation with concentration and time, which could be inhibited by SB202190-p38MAPK. When the expression of SB202190 increased, the inhibition increased. Compared with 0 μmol/L, concentration of each group was inhibited more significantly, for 1 μmol/L group(P<0.05), for 10, 20, 30 μmol/L groups(P <0.01). After PGN activated BV2 cells, the activation of p38MAPK phosphorylation at each time point was significantly different from the control group(P<0.01). Conclusion The endocytosis of Aβ42 oligomer increased after BV2 cells was activated by PGN, which can be inhibited by mFPR2, so it is speculated that endocytosis of Aβ in BV2 cells may have relation with the expression of mFPR2. PGN could lead to the increase of mFPR2 mRNA expression in BV2 cells, which may participate in the endocytosis of Aβ after BV2 cells are activated. PGN can lead to the increase of p38MAPK expression in BV2, and its inhibitor can decrease the expression of mFPR2 mRNA, which may be the mechanism of endocytosis of Aβ after BV2 cells are activated.

Key words: peptidoglycan, microglia, Aβ_1-42 oligomer, p38 mitogen-activated protein kinase, formyl peptide receptor/mouse homologue formyl peptide receptor

中图分类号:

R 592

姜新;相荣才;白丽娟;张贺敏;陈晓虹;马恩龙. PGN对BV2细胞内吞Aβ寡聚体的影响[J]. 首都医科大学学报, 2011, 32(4): 501-508.

JIANG Xin;XIANG Rong-cai;BAI Li-juan;ZHANG He-min;CHEN Xiao-hong;MA En-long. Influence of peptidoglycan on BV2 cells after endocytosis of amyloid protein β oligomers[J]. Journal of Capital Medical University, 2011, 32(4): 501-508.

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PGN对BV2细胞内吞Aβ寡聚体的影响

Influence of peptidoglycan on BV2 cells after endocytosis of amyloid protein β oligomers

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