PrP106-126及Aβ1-42同步诱导BV-2小胶质细胞趋化及增殖活性的研究

doi:10.11843/j.issn.0366-6964.2014.10.017

Abstract

Abstract:

Transmissible spongiform encephalopathies (TSEs) and Alzheimer’s disease (AD) belong to a growing family of neurodegenerative disorders that is characterized by the generation of toxic protein aggregates in affected brains (PrP^Sc and Aβ in TSEs and AD，respectively).At present，clinical and experimental evidence indicates the coexistence of PrP and Aβ amyloid deposits in affected brain tissues.Based on these pathological and mechanistic similarities，relationship between TSEs and AD should be further investigated.In this study，we examined the activation of BV-2 microglial chemotaxis and proliferation as well as BV-2 cell secretion of MCP-1 and TGF-β1 after treatment with aggregated forms of PrP^106-126 and Aβ_1-42 (separately and together) in vitro in an attempt to understand how protein aggregates can modulate microglial processes in TSEs and AD.We treated BV-2 microglia with PrP^106-126 or Aβ_1-42 peptides individually at thee different concentrations (25-100 μmol•L^－1 PrP^106-126 and 2.5-10 μmol•L^－1 Aβ_1-42) or with a mixture of PrP^106-126 and Aβ_1-42 peptides at specified concentrations for 6-24 h.BV-2 microglia chemotaxis，proliferation，and MCP-1 and TGF-β1 secretion were measured and compared between treatments.The results demonstrate that PrP^106-126 and Aβ_1-42 peptides induce increases in all four parameters from 6-12 h.However，the measured indices plateaued beyond 12 h in BV-2 cells treated >50 μmol•L^－1 PrP^106-126 or >5 μmol•L^－1 Aβ_1-42，with the exception of TGF-β1 secretion，which continued to increase gradually.Overall，the results of this study indicated that PrP^106-126 and Aβ_1-42 peptides induce increases in all four parameters from 6-12 h and these two peptides have obviously antagonistic effects in inducing microglial chemotaxis and proliferation simultaneously at the protein level.

CLC Number:

S852.659.7

TU Jian，YANG Li-feng，QI Ke-zong，ZHOU Xiang-mei，YIN Xiao-min，ZHAO De-ming. PrP^106-126 and Aβ_1-42 Peptides Induce Simultaneously BV-2 Microglia Chemotaxis and Proliferation[J]. ACTA VETERINARIA ET ZOOTECHNICA SINICA, 2014, 45(10): 1699-1710.

0
/ / Recommend

Add to citation manager EndNote|Reference Manager|ProCite|BibTeX|RefWorks

URL: https://www.xmsyxb.com/EN/10.11843/j.issn.0366-6964.2014.10.017

https://www.xmsyxb.com/EN/Y2014/V45/I10/1699

References

［1］KONTUREK P C，BAZELA K，KUKHARSKYY V，et al.Helicobacter pylori upregulates prion protein expression in gastric mucosa：a possible link to prion disease ［J］.World J Gastroenterol，2005，11(48)：7651-7656.
［2］SAFAR J，ROLLER P P，GAJDUSEK D C，et al.Conformational transitions，dissociation，and unfolding of scrapie amyloid (prion) protein ［J］. J Biol Chem，1993，268(27)：20276-20284.
［3］LE Y，YAZAWA H，GONG W，et al.Cutting edge：The neurotoxic prion peptide fragment PrP_106-126 is a chemotactic agonist for the G protein-coupled receptor formyl peptide receptor-like 1 ［J］.J Immunol，2001，166(3)：1448-1451.
［4］HUANG H C，JIANG Z F.Accumulated amyloid-beta peptide and hyperphosphorylated tau protein：relationship and links in Alzheimer’s disease ［J］. J Alzheimers Dis，2009，16 (1)：15-27.
［5］ANDREASEN N，BLENNOW K.CSF biomarkers for mild cognitive impairment and early Alzheimer’s disease ［J］. Clin Neurol Neurosurg，2005，107(3)：165-173.
［6］ARISPE N，DOH M.Plasma membrane cholesterol controls the cytotoxicity of Alzheimer’s disease Aβ(1-40) and (1-42) peptides ［J］.FASEB J，2002，16(12):1526-1536.
［7］CHROMY B A，NOWAK R J，LAMBERT M P，et al.Self-assembly of Abeta(1-42) into globular neurotoxins ［J］.Biochemistry，2003，42(44)：12749-12760.
［8］POWERS J M，LIU Y，HAIR L S，et al.Concomitant Creutzfeldt-Jakob and Alzheimer diseases ［J］.Acta Neuropathol，1991，83(1)：95-98.
［9］HAINFELLNER J A，WANSCHITZ J，JELLINGER K，et al.Coexistence of Alzheimer-type neuropathology in Creutzfeldt-Jakob disease ［J］.Acta Neuropathol，1998，96(2):116-122.
［10］VOIGTLÄNDER T，KLÖPPEL S，BIRNER P，et al.Marked increase of neuronal prion protein immunoreactivity in Alzheimer's disease and human prion diseases ［J］.Acta Neuropathol，2001，101(5)：417-423.
［11］CISSE M，MUCKE L.Alzheimer’s disease：A prion protein connection ［J］.Nature，2009，457 (7233)：1090-1091.
［12］VEERHUIS R，BOSHUIZEN R S，FAMILIAN A.Amyloid associated proteins in Alzheimer's and prion disease ［J］.Curr Drug Targets CNS Neurol Disord，2005，4(3)：235-248.
［13］LAURÉN J，GIMBEL D A，NYGAARD H B，et al.Cellular prion protein mediates impairment of synaptic plasticity by amyloid-β oligomers ［J］.Nature，2009，457 (7233)：1128-1132.
［14］TSUCHIYA K，YAGISHITA S，IKEDA K，et al.Coexistence of CJD and Alzheimer's disease：An autopsy case showing typical clinical features of CJD ［J］.Neuropathology，2004，24(1)：46-55.
［15］FERRER I，BLANCO R，CARMONA M，et al.Prion protein expression in senile plaques in Alzheimer’s disease ［J］.Acta Neuropathol，2001，101 (1)：49-56.
［16］BLASI E，BARLUZZI R，BOCCHINI V，et al.Immortalization of murine microglial cells by a v-raf/v-myc carrying retrovirus ［J］.J Neuroimmunol，1990，27(2-3):229-237.
［17］PRAT E，BARON P，MEDA L，et al.The human astrocytoma cell line U373MG produces monocyte chemotactic protein (MCP)-1 upon stimulation with β-amyloid protein ［J］.Neurosci Lett，2000，283(3)：177-180.
［18］CIESIELSKI-TRESKA J，GRANT N J，ULRICH G，et al.Fibrillar prion peptide (106-126) and scrapie prion protein hamper phagocytosis in microglia ［J］.Glia，2004，46(2)：101-115.
［19］ROTA E，BELLONE G，ROCCA P，et al.Increased intrathecal TGF-β1，but not IL-12，IFN-γ and IL-10 levels in Alzheimer’s disease patients ［J］.Neurol Sci，2006，27(1)：33-39.
［20］STINE W B Jr，DAHLGREN K N，KRAFFT G A，et al.In vitro characterization of conditions for amyloid-β peptide oligomerization and fibrillogenesis ［J］.J Biol Chem，2003，278(13)：11612-11622.
［21］BAMBERGER M E，HARRIS M E，MCDONALD D R，et al.A cell surface receptor complex for fibrillar β-amyloid mediates microglial activation ［J］.J Neurosci，2003，23(7)：2665-2674.
［22］BURDICK D，SOREGHAN B，KWON M，et al.Assembly and aggregation properties of synthetic Alzheimer’s A4/β amyloid peptide analogs ［J］.J Biol Chem，1992，267(1)：546-554.
［23］DUNZENDORFER S，KASER A，MEIERHOFER C，et al.Dendritic cell migration in different micropore filter assays ［J］.Immunol Lett，2000，71(1)：5-11.
［24］KANEIDER N C，KASER A，DUNZENDORFER S，et al.Sphingosine kinase-dependent migration of immature dendritic cells in response to neurotoxic prion protein fragment ［J］.J Virol，2003，77(9)：5535-5539.
［25］KALLITHRAKA S，BAKKER J，CLIFFORD M N，et al.Correlations between saliva protein composition and some T-I parameters of astringency ［J］. Food Qual Prefer，2001，12(2)：145-152.
［26］YANG L F，ZHOU X M，YANG J M，et al.Aspirin inhibits cytotoxicity of prion peptide PrP106-126 to neuronal cells associated with microglia activation in vitro ［J］.J Neuroimmunol，2008，199(1-2)：10-17.
［27］BRANDENBURG L O，LUCIUS R，TAMEH ABOLFAZL A，et al.Internalization and signal transduction of PrP_106-126 in neuronal cells ［J］.Ann Anat，2009，191 (5)：459-468.
［28］BATE C，VEERHUIS R，EIKELENBOOM P，et al.Microglia kill amyloid-β1-42 damaged neurons by a CD14-dependent process ［J］.Neuroreport，2004，15(9)：1427-1430.
［29］WANG Z F，WEI Z L，LI X M，et al.P1-241 Aβ1-42 can kill murine N2A neuroblastoma cells at nanomolar concentration ［J］.Neurobiol Aging，2004，25(S2)：S165-S171.
［30］SUN Y X，CRISBY M，LINDGREN S，et al.Pravastatin inhibits pro-inflammatory effects of Alzheimer’s peptide Aβ1-42 in glioma cell culture in vitro ［J］.Pharmacol Res，2003，47(2)：119-126.
［31］KREUTZBERG G W.Microglia：a sensor for pathological events in the CNS ［J］.Trends Neurosci，1996，19(8)：312-318.

[1]	ZHANG Tian-liang，WU Run，YANG Run-xia，WEI Jiao，WAN Xue-rui，LIU Xia，LIU Lei，ZHANG Xiao-li. Clone of Chicken Prion-like Doppel Gene and the Analysis of Its Interrelation with PrP^C [J]. ACTA VETERINARIA ET ZOOTECHNICA SINICA, 2015, 46(8): 1425-1431.
[2]	SONG Zhi-qi，ZHAO Wen-jie，YANG Li-feng,WANG Yun-sheng,ZHU Ting,CHENG Guang-yu,ZHOU Xiang-mei,ZHAO De-ming . Overexpression of BAT3 Alleviates Prion Protein Fragment PrP106-126-Induced Neuronal Apoptosis [J]. ACTA VETERINARIA ET ZOOTECHNICA SINICA, 2015, 46(5): 841-848.
[3]	WU Xiao-dong，ZOU Yan-li，LIU Yu-tian，LI Jin-ming，ZHANG Yong-qiang，LIU Shan，WANG Zhi-liang. Pathogenic Characteristics of Mouse-adapted Scrapie Strain RML Propagated in N2a Cell Line [J]. ACTA VETERINARIA ET ZOOTECHNICA SINICA, 2015, 46(2): 257-263.
[4]	YUAN Fang-zhong，GENG Mei-ying，ZHAO De-ming. The Damage Mechanism of Neuroblastoma Cells Mitochondria in the Presence of PrP106-126 Peptide [J]. ACTA VETERINARIA ET ZOOTECHNICA SINICA, 2014, 45(9): 1526-1530.

PrP^106-126 and Aβ_1-42 Peptides Induce Simultaneously BV-2 Microglia Chemotaxis and Proliferation

PDF (PC)

Knowledge

Abstract

Cite this article

share this article

References

Related Articles 4

Recommended Articles

Metrics

Comments

PrP106-126 and Aβ1-42 Peptides Induce Simultaneously BV-2 Microglia Chemotaxis and Proliferation

PDF (PC)

Knowledge

Abstract

Cite this article

share this article

References

Related Articles 4

Recommended Articles

Metrics

Comments

PrP^106-126 and Aβ_1-42 Peptides Induce Simultaneously BV-2 Microglia Chemotaxis and Proliferation