Uptake of Aβ by OATPs might be a new pathophysiological mechanism of Alzheimer disease
Abstract Background The accumulation of neurotoxic amyloid-beta (Aβ) in the brain is a characteristic of Alzheimer's disease (AD), at the same time, it is possible alterations of liver function could affect brain Aβ levels through changes in blood Aβ concentration. Over the last decade, a numbe...
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| Format: | Article |
| Language: | English |
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BMC
2021-09-01
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| Series: | BMC Neuroscience |
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| Online Access: | https://doi.org/10.1186/s12868-021-00658-9 |
| _version_ | 1818729176332500992 |
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| author | Jinhua Wen Menghua Zhao Wenxiong Sun Xiaohua Cheng Luyi Yu Duanwen Cao Pu Li |
| author_facet | Jinhua Wen Menghua Zhao Wenxiong Sun Xiaohua Cheng Luyi Yu Duanwen Cao Pu Li |
| author_sort | Jinhua Wen |
| collection | DOAJ |
| description | Abstract Background The accumulation of neurotoxic amyloid-beta (Aβ) in the brain is a characteristic of Alzheimer's disease (AD), at the same time, it is possible alterations of liver function could affect brain Aβ levels through changes in blood Aβ concentration. Over the last decade, a number of reports have shown that P-glycoprotein (encoded by ABC1B1) actively mediates the efflux transport of Aβ peptides. However, the mechanism by which Aβ peptides enter the cells is not clear. In the preliminary study, we found that the protein expression of organic anion transporting Polypeptide 1a4 (OATP1B1) in the liver tissue of mice with AD was significantly higher than that in the normal mice. In contrast, the protein expression of Oatp1a4 in the brain significantly decreased in mice with AD. OATP1B1, an important drug transporter might be related to the pathophysiology of AD. Results In this study, we established an OATP1B1-GFP-HEK293T cell model to confirm the OATP1B1 mediated transport of Aβ1-42. Compared to the control group of GFP-HEK293Tcells, the uptake of Aβ1-42 protein in the OATP1B1-GFP-HEK293T group increased significantly with the increase in concentration of Aβ1-42, and also increased significantly with an increase in the duration of incubation. Similar results were observed in the flow cytometry experiment, and the uptake of Aβ1-42in HEK293T-OATP1B1 cells was almost twice that in the control group. These results indicate that OATPs may act as an important “carrier” for the transport of Aβ1-42 from the blood to the tissues, including liver and brain. Conclusions This is a novel and interesting finding and OATP1B1 can be investigated as a new treatment target for AD. |
| first_indexed | 2024-12-17T22:41:43Z |
| format | Article |
| id | doaj.art-610482a3d2864118b750b8cde8b4d428 |
| institution | Directory Open Access Journal |
| issn | 1471-2202 |
| language | English |
| last_indexed | 2024-12-17T22:41:43Z |
| publishDate | 2021-09-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Neuroscience |
| spelling | doaj.art-610482a3d2864118b750b8cde8b4d4282022-12-21T21:29:54ZengBMCBMC Neuroscience1471-22022021-09-012211910.1186/s12868-021-00658-9Uptake of Aβ by OATPs might be a new pathophysiological mechanism of Alzheimer diseaseJinhua Wen0Menghua Zhao1Wenxiong Sun2Xiaohua Cheng3Luyi Yu4Duanwen Cao5Pu Li6Departmentof GCP/Psychosomatic Medicine, The First Affiliated Hospital of Nanchang UniversitySchool of Pharmacy, Nanchang UniversityDepartmentof GCP/Psychosomatic Medicine, The First Affiliated Hospital of Nanchang UniversityDepartmentof GCP/Psychosomatic Medicine, The First Affiliated Hospital of Nanchang UniversityDepartmentof GCP/Psychosomatic Medicine, The First Affiliated Hospital of Nanchang UniversityDepartmentof GCP/Psychosomatic Medicine, The First Affiliated Hospital of Nanchang UniversityDepartmentof GCP/Psychosomatic Medicine, The First Affiliated Hospital of Nanchang UniversityAbstract Background The accumulation of neurotoxic amyloid-beta (Aβ) in the brain is a characteristic of Alzheimer's disease (AD), at the same time, it is possible alterations of liver function could affect brain Aβ levels through changes in blood Aβ concentration. Over the last decade, a number of reports have shown that P-glycoprotein (encoded by ABC1B1) actively mediates the efflux transport of Aβ peptides. However, the mechanism by which Aβ peptides enter the cells is not clear. In the preliminary study, we found that the protein expression of organic anion transporting Polypeptide 1a4 (OATP1B1) in the liver tissue of mice with AD was significantly higher than that in the normal mice. In contrast, the protein expression of Oatp1a4 in the brain significantly decreased in mice with AD. OATP1B1, an important drug transporter might be related to the pathophysiology of AD. Results In this study, we established an OATP1B1-GFP-HEK293T cell model to confirm the OATP1B1 mediated transport of Aβ1-42. Compared to the control group of GFP-HEK293Tcells, the uptake of Aβ1-42 protein in the OATP1B1-GFP-HEK293T group increased significantly with the increase in concentration of Aβ1-42, and also increased significantly with an increase in the duration of incubation. Similar results were observed in the flow cytometry experiment, and the uptake of Aβ1-42in HEK293T-OATP1B1 cells was almost twice that in the control group. These results indicate that OATPs may act as an important “carrier” for the transport of Aβ1-42 from the blood to the tissues, including liver and brain. Conclusions This is a novel and interesting finding and OATP1B1 can be investigated as a new treatment target for AD.https://doi.org/10.1186/s12868-021-00658-9OATPsAlzheimer diseaseBeta-amyloid |
| spellingShingle | Jinhua Wen Menghua Zhao Wenxiong Sun Xiaohua Cheng Luyi Yu Duanwen Cao Pu Li Uptake of Aβ by OATPs might be a new pathophysiological mechanism of Alzheimer disease BMC Neuroscience OATPs Alzheimer disease Beta-amyloid |
| title | Uptake of Aβ by OATPs might be a new pathophysiological mechanism of Alzheimer disease |
| title_full | Uptake of Aβ by OATPs might be a new pathophysiological mechanism of Alzheimer disease |
| title_fullStr | Uptake of Aβ by OATPs might be a new pathophysiological mechanism of Alzheimer disease |
| title_full_unstemmed | Uptake of Aβ by OATPs might be a new pathophysiological mechanism of Alzheimer disease |
| title_short | Uptake of Aβ by OATPs might be a new pathophysiological mechanism of Alzheimer disease |
| title_sort | uptake of aβ by oatps might be a new pathophysiological mechanism of alzheimer disease |
| topic | OATPs Alzheimer disease Beta-amyloid |
| url | https://doi.org/10.1186/s12868-021-00658-9 |
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