Suppression of amyloid‐β secretion from neurons by cis ‐9, trans ‐11‐octadecadienoic acid, an isomer of conjugated linoleic acid
| Autor: | Shoichi Kinoshita, Taisuke Tomita, Yoshitake Sano, Junken Aoki, Takaomi C. Saido, Kazunori Kikuchi, Yuriko Sobu, Shunji Natori, Kuniyuki Kano, Toshiharu Suzuki, Hidenori Taru, Hiroto Komano, Saori Hata, Haruka Saito, Takashi Saito |
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| Rok vydání: | 2021 |
| Předmět: |
Male
Endosome Conjugated linoleic acid Endosomes Cleavage (embryo) Biochemistry Presenilin Linoleic Acid Amyloid beta-Protein Precursor Mice Cellular and Molecular Neuroscience chemistry.chemical_compound Phosphatidylcholine mental disorders Animals Aspartic Acid Endopeptidases Linoleic Acids Conjugated Secretion Cells Cultured Neurons chemistry.chemical_classification Amyloid beta-Peptides integumentary system food and beverages Colocalization Immunohistochemistry Cell biology Mice Inbred C57BL Enzyme chemistry Dietary Supplements Phosphatidylcholines lipids (amino acids peptides and proteins) Amyloid Precursor Protein Secretases |
| Zdroj: | Journal of Neurochemistry. 159:603-617 |
| ISSN: | 1471-4159 0022-3042 |
| Popis: | Two common conjugated linoleic acids (LAs), cis-9, trans-11 CLA (c9,t11 CLA) and trans-10, cis-12 CLA (t10,c12 CLA), exert various biological activities. However, the effect of CLA on the generation of neurotoxic amyloid-β (Aβ) protein remains unclear. We found that c9,t11 CLA significantly suppressed the generation of Aβ in mouse neurons. CLA treatment did not affect the level of β-site APP-cleaving enzyme 1 (BACE1), a component of active γ-secretase complex presenilin 1 amino-terminal fragment, or Aβ protein precursor (APP) in cultured neurons. BACE1 and γ-secretase activities were not directly affected by c9,t11 CLA. Localization of BACE1 and APP in early endosomes increased in neurons treated with c9,t11 CLA; concomitantly, the localization of both proteins was reduced in late endosomes, the predominant site of APP cleavage by BACE1. The level of CLA-containing phosphatidylcholine (CLA-PC) increased dramatically in neurons incubated with CLA. Incorporation of phospholipids containing c9,t11 CLA, but not t10,c12 CLA, into the membrane may affect the localization of some membrane-associated proteins in intracellular membrane compartments. Thus, in neurons treated with c9,t11 CLA, reduced colocalization of APP with BACE1 in late endosomes may decrease APP cleavage by BACE1 and subsequent Aβ generation. Our findings suggest that the accumulation of c9,t11 CLA-PC/LPC in neuronal membranes suppresses the production of neurotoxic Aβ in neurons. |
| Databáze: | OpenAIRE |
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