Insulin promotes amyloid precursor protein metabolism in an Alzheimer's disease cell model
Objective To investigate how insulin affects the metabolism of amyloid precursor protein (APP) in a cell model of Alzheimer's disease (AD). Methods Human neuroblastoma SH-SY5Y cells and the nonneural cell lines HEK293 and 2EB2 were treated with different concentrations of insulin for 48 h, and...
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Editorial Office of Journal of Third Military Medical University
2020-06-01
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Series: | Di-san junyi daxue xuebao |
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Online Access: | http://aammt.tmmu.edu.cn/Upload/rhtml/202001195.htm |
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zho |
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DOAJ |
author |
HU Rong WANG Dan LOU Dandan LI Tingyu ZHOU Weihui SONG Weihong |
spellingShingle |
HU Rong WANG Dan LOU Dandan LI Tingyu ZHOU Weihui SONG Weihong Insulin promotes amyloid precursor protein metabolism in an Alzheimer's disease cell model Di-san junyi daxue xuebao alzheimer's disease insulin amyloid precursor protein β-amyloid akt/gsk3β |
author_facet |
HU Rong WANG Dan LOU Dandan LI Tingyu ZHOU Weihui SONG Weihong |
author_sort |
HU Rong |
title |
Insulin promotes amyloid precursor protein metabolism in an Alzheimer's disease cell model |
title_short |
Insulin promotes amyloid precursor protein metabolism in an Alzheimer's disease cell model |
title_full |
Insulin promotes amyloid precursor protein metabolism in an Alzheimer's disease cell model |
title_fullStr |
Insulin promotes amyloid precursor protein metabolism in an Alzheimer's disease cell model |
title_full_unstemmed |
Insulin promotes amyloid precursor protein metabolism in an Alzheimer's disease cell model |
title_sort |
insulin promotes amyloid precursor protein metabolism in an alzheimer's disease cell model |
publisher |
Editorial Office of Journal of Third Military Medical University |
series |
Di-san junyi daxue xuebao |
issn |
1000-5404 |
publishDate |
2020-06-01 |
description |
Objective To investigate how insulin affects the metabolism of amyloid precursor protein (APP) in a cell model of Alzheimer's disease (AD). Methods Human neuroblastoma SH-SY5Y cells and the nonneural cell lines HEK293 and 2EB2 were treated with different concentrations of insulin for 48 h, and the changes in cell viability were evaluated with CCK-8 assay. The expression levels of APP, C-terminal fragment of APP (CTF), β-site APP cleaving enzyme 1 (BACE1), the α-secretase ADAM10 (a disintegrin and metalloproteinase 10) and γ-secretase presenilin 1 (PS1) in the cells were detected using Western blotting. ELISA was used to determine the cellular expression levels of Aβ40 and Aβ42. The key signaling pathways mediated by insulin were screened using a protein chip. The effect of insulin on protein phosphorylation levels of AKT and GSK3β pathways was examined by detecting p-AKT and p-GSK3β expression in the cells with Western blotting. Results Treatment with insulin below 10 μmol/L did not obviously affect the viability of the cells (P>0.05). Western blotting showed that treatment with 1.00 and 10.00 μmol/L insulin significantly increased the protein expression of APP and CTF (P < 0.05) and also the expression of BACE1, a key enzyme for APP metabolism (P < 0.05). The results of ELISA demonstrated that the expression level of Aβ42 increased significantly in the cells following treatment with 1.00 and 10.00 μmol/L insulin (P < 0.05). The protein microarray data identified GSK3β as a potential target of insulin. Western blot analysis showed that the expression of p-AKT and p-GSK3β proteins was down-regulated following insulin treatment, but the differences were not statistically significant (P>0.05). Conclusion Insulin promotes the metabolism of APP into CTF and Aβ42, which play certain rolesin pathogenesis of AD. |
topic |
alzheimer's disease insulin amyloid precursor protein β-amyloid akt/gsk3β |
url |
http://aammt.tmmu.edu.cn/Upload/rhtml/202001195.htm |
work_keys_str_mv |
AT hurong insulinpromotesamyloidprecursorproteinmetabolisminanalzheimersdiseasecellmodel AT wangdan insulinpromotesamyloidprecursorproteinmetabolisminanalzheimersdiseasecellmodel AT loudandan insulinpromotesamyloidprecursorproteinmetabolisminanalzheimersdiseasecellmodel AT litingyu insulinpromotesamyloidprecursorproteinmetabolisminanalzheimersdiseasecellmodel AT zhouweihui insulinpromotesamyloidprecursorproteinmetabolisminanalzheimersdiseasecellmodel AT songweihong insulinpromotesamyloidprecursorproteinmetabolisminanalzheimersdiseasecellmodel |
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1721442717499654144 |
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doaj-efbe3a3e7b9546c881c2ab80dc875f9f2021-05-13T07:40:04ZzhoEditorial Office of Journal of Third Military Medical UniversityDi-san junyi daxue xuebao1000-54042020-06-0142121201120810.16016/j.1000-5404.202001195Insulin promotes amyloid precursor protein metabolism in an Alzheimer's disease cell model HU Rong0WANG Dan1LOU Dandan2LI Tingyu3ZHOU Weihui4SONG Weihong5Institute of Pediatrics, Key Laboratory of Child Development and Disorders of Ministry of Education, Chongqing International Science and Technology Cooperation Base for Child Development and Critical Disorders, Chongqing Key Laboratory of Pediatrics, Children's Hospital of Chongqing Medical University, Chongqing, 400014, China Institute of Pediatrics, Key Laboratory of Child Development and Disorders of Ministry of Education, Chongqing International Science and Technology Cooperation Base for Child Development and Critical Disorders, Chongqing Key Laboratory of Pediatrics, Children's Hospital of Chongqing Medical University, Chongqing, 400014, China Institute of Pediatrics, Key Laboratory of Child Development and Disorders of Ministry of Education, Chongqing International Science and Technology Cooperation Base for Child Development and Critical Disorders, Chongqing Key Laboratory of Pediatrics, Children's Hospital of Chongqing Medical University, Chongqing, 400014, China Institute of Pediatrics, Key Laboratory of Child Development and Disorders of Ministry of Education, Chongqing International Science and Technology Cooperation Base for Child Development and Critical Disorders, Chongqing Key Laboratory of Pediatrics, Children's Hospital of Chongqing Medical University, Chongqing, 400014, China Institute of Pediatrics, Key Laboratory of Child Development and Disorders of Ministry of Education, Chongqing International Science and Technology Cooperation Base for Child Development and Critical Disorders, Chongqing Key Laboratory of Pediatrics, Children's Hospital of Chongqing Medical University, Chongqing, 400014, China Institute of Pediatrics, Key Laboratory of Child Development and Disorders of Ministry of Education, Chongqing International Science and Technology Cooperation Base for Child Development and Critical Disorders, Chongqing Key Laboratory of Pediatrics, Children's Hospital of Chongqing Medical University, Chongqing, 400014, China Objective To investigate how insulin affects the metabolism of amyloid precursor protein (APP) in a cell model of Alzheimer's disease (AD). Methods Human neuroblastoma SH-SY5Y cells and the nonneural cell lines HEK293 and 2EB2 were treated with different concentrations of insulin for 48 h, and the changes in cell viability were evaluated with CCK-8 assay. The expression levels of APP, C-terminal fragment of APP (CTF), β-site APP cleaving enzyme 1 (BACE1), the α-secretase ADAM10 (a disintegrin and metalloproteinase 10) and γ-secretase presenilin 1 (PS1) in the cells were detected using Western blotting. ELISA was used to determine the cellular expression levels of Aβ40 and Aβ42. The key signaling pathways mediated by insulin were screened using a protein chip. The effect of insulin on protein phosphorylation levels of AKT and GSK3β pathways was examined by detecting p-AKT and p-GSK3β expression in the cells with Western blotting. Results Treatment with insulin below 10 μmol/L did not obviously affect the viability of the cells (P>0.05). Western blotting showed that treatment with 1.00 and 10.00 μmol/L insulin significantly increased the protein expression of APP and CTF (P < 0.05) and also the expression of BACE1, a key enzyme for APP metabolism (P < 0.05). The results of ELISA demonstrated that the expression level of Aβ42 increased significantly in the cells following treatment with 1.00 and 10.00 μmol/L insulin (P < 0.05). The protein microarray data identified GSK3β as a potential target of insulin. Western blot analysis showed that the expression of p-AKT and p-GSK3β proteins was down-regulated following insulin treatment, but the differences were not statistically significant (P>0.05). Conclusion Insulin promotes the metabolism of APP into CTF and Aβ42, which play certain rolesin pathogenesis of AD.http://aammt.tmmu.edu.cn/Upload/rhtml/202001195.htmalzheimer's diseaseinsulinamyloid precursor proteinβ-amyloidakt/gsk3β |