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Cited by 20Alzheimer's disease research and treatmentsCell Adhesion Molecules ResearchNeuroinflammation and Neurodegeneration Mechanisms

αν and β1 Integrins Mediate Aβ-Induced Neurotoxicity in Hippocampal Neurons via the FAK Signaling Pathway

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Han, Hai-Yan, Zhang, Jin-Ping, Ji, Su-Qiong, Liang, Qi-Ming, Kang, Hui-Cong, Tang, Rong-Hua, Zhu, Sui-Qiang, Xue, Zheng·2013·PLoS ONE
DOI 10.1371/journal.pone.0064839PMC PMC3670848
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Abstract

αν and β1 integrins mediate Aβ-induced neurotoxicity in primary hippocampal neurons. We treated hippocampal neurons with 2.5 µg/mL 17E6 and 5 µg/mL ab58524, which are specific αν and β1 integrin antagonists, respectively, for 42 h prior to 10 µM Aβ treatment. Next, we employed small interfering RNA (siRNA) to silence focal adhesion kinase (FAK), a downstream target gene of integrins. The siRNAs were designed with a target sequence, an MOI of 10 and the addition of 5 µg/mL polybrene. Under these conditions, the neurons were transfected and the apoptosis of different cell types was detected. Moreover, we used real-time PCR and Western blotting analyses to detect the expression of FAK and ρFAK genes in different cell types and investigated the underlying mechanism and signal pathway by which αν and β1 integrins mediate Aβ-induced neurotoxicity in hippocampal neurons. An MTT assay showed that both 17E6 and ab58524 significantly increased cell viability compared with the Aβ-treated neurons (P<0.01 and P<0.05, respectively). However, this protective effect was markedly attenuated after transfection with silencing FAK (siFAK). Moreover, TUNEL immunostaining and flow cytometry indicated that both 17E6 and ab58524 significantly protected hippocampal neurons against apoptosis induced by Aβ (P<0.05) compared with the Aβ-treated cells. However, this protective effect was reversed with siFAK treatment. Both the gene and protein expression of FAK increased after Aβ treatment. Interestingly, as the gene and protein levels of FAK decreased, the ρFAK protein expression markedly increased. Furthermore, both the gene and protein expression of FAK and ρFAK were significantly diminished. Thus, we concluded that both αν and β1 integrins interfered with Aβ-induced neurotoxicity in hippocampal neurons and that this mechanism partially contributes to the activation of the Integrin-FAK signaling pathway.

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Cited by

Sorted by citations

Authors
Han, H.-Y., Zhang, J.-P., Ji, S.-Q., Liang, Q.-M., Kang, H.-C., Tang, R.-H., Zhu, S.-Q., & Xue, Z.
Affiliations
Tongji Hospital (CN)
Corresponding author
Xue, Zheng
ORCID
Xue, Zheng
Venue
PLoS ONE
Publisher
Public Library of Science (PLoS)
Published
2013-06-03
Volume
8
Issue
6
Pages
e64839
ISSN
1932-6203 (ISSN-L)
DOI
10.1371/journal.pone.0064839
PMC
PMC3670848
OpenAlex
W1987777832
Cited by
20
References
3
Citations by year
2025: 2 · 2024: 1 · 2022: 2 · 2021: 1 · 2020: 1 · 2019: 2 · 2018: 5 · 2016: 1 · 2014: 4 · 2013: 1
FWCI
1.24
Type
journal article
Language
en
Open access
Licence
Locations
  • PLoS ONE (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, other-oa)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • Figshare (submittedVersion, cc-by)
Topics
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Health Sciences › Medicine › Immunology and Allergy › Cell Adhesion Molecules Research
  • Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
Keywords
ITGAV, beta1 integrin, amyloid-beta, hippocampal neurons, focal adhesion kinase, apoptosis, integrin antagonists, Alzheimer's disease
MeSH terms
Animals, Cell Survival, Flow Cytometry, Gene Expression Regulation, Hippocampus, Microtubule-Associated Proteins, Neurons, Neurotoxins, Phosphorylation, Transfection, Signal Transduction, Lentivirus, Amyloid beta-Peptides, Apoptosis, Neuroprotective Agents, Integrin beta1, In Situ Nick-End Labeling, RNA, Small Interfering, Integrin alphaV, Rats, Focal Adhesion Protein-Tyrosine Kinases

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