Involvement of insulin-degrading enzyme in insulin- and atrial natriuretic peptide-sensitive internalization of amyloid-β peptide in mouse brain capillary endothelial cells

Autor: Tetsuya Terasaki, Yuki Katsukura, Miho Funaki, Sho Murata, Masanori Tachikawa, Shingo Ito, Sumio Ohtsuki, Hiroya Suzuki
Rok vydání: 2013
Předmět:
Male
medicine.medical_specialty
Time Factors
medicine.drug_class
medicine.medical_treatment
media_common.quotation_subject
Peptide
Biology
Blood–brain barrier
Insulysin
chemistry.chemical_compound
Mice
Atrial natriuretic peptide
Internal medicine
medicine
Insulin-degrading enzyme
Natriuretic peptide
Animals
Insulin
RNA
Small Interfering
Internalization
Cells
Cultured
media_common
chemistry.chemical_classification
Amyloid beta-Peptides
Dose-Response Relationship
Drug
General Neuroscience
Phosphoramidon
Brain
Endothelial Cells
General Medicine
Peptide Fragments
Mice
Inbred C57BL
Psychiatry and Mental health
Clinical Psychology
medicine.anatomical_structure
Endocrinology
chemistry
Gene Expression Regulation
Blood-Brain Barrier
Geriatrics and Gerontology
Receptors
Atrial Natriuretic Factor
Atrial Natriuretic Factor
Zdroj: Journal of Alzheimer's disease : JAD. 38(1)
ISSN: 1875-8908
Popis: Cerebral clearance of amyloid-β peptide (Aβ), which is implicated in Alzheimer's disease, involves elimination across the blood-brain barrier (BBB), and we previously showed that an insulin-sensitive process is involved in the case of Aβ1-40. The purpose of this study was to clarify the molecular mechanism of the insulin-sensitive Aβ1-40 elimination across mouse BBB. An in vivo cerebral microinjection study demonstrated that [125I]hAβ1-40 elimination from mouse brain was inhibited by human natriuretic peptide (hANP), and [125I]hANP elimination was inhibited by hAβ1-40, suggesting that hAβ1-40 and hANP share a common elimination process. Internalization of [125I]hAβ1-40 into cultured mouse brain capillary endothelial cells (TM-BBB4) was significantly inhibited by either insulin, hANP, other natriuretic peptides or insulin-degrading enzyme (IDE) inhibitors, but was not inhibited by phosphoramidon or thiorphan. Although we have reported the involvement of natriuretic peptide receptor C (Npr-C) in hANP internalization, cells stably expressing Npr-C internalized [125I]hANP but not [125I]hAβ1-40, suggesting that there is no direct interaction between Npr-C and hAβ1-40. IDE was detected in plasma membrane of TM-BBB4 cells, and internalization of [125I]hAβ1-40 by TM-BBB4 cells was reduced by IDE-targeted siRNAs. We conclude that elimination of hAβ1-40 from mouse brain across the BBB involves an insulin- and ANP-sensitive process, mediated by IDE expressed in brain capillary endothelial cells.
Databáze: OpenAIRE
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