DHA attenuates Aβ-induced necroptosis through the RIPK1/RIPK3 signaling pathway in THP-1 monocytes
| Autor: | Tianming Lü, Zhenlin Mao, Wenyi Xie, Shiqi Yuan, Jiafa Zhang, Huan Li, Yuanyuan Wang, Weibing Xie, Canhong Yang, Zibo cai |
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| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
MAPK/ERK pathway Docosahexaenoic Acids Cell Survival THP-1 Cells p38 mitogen-activated protein kinases Necroptosis Apoptosis RM1-950 Neuroprotection Monocytes 03 medical and health sciences RIPK1 0302 clinical medicine medicine Docosahexaenoic acid (DHA) Humans Pharmacology Neurons Amyloid beta-Peptides CD11b Antigen Chemistry Monocyte Cell Differentiation General Medicine MAPK Peptide Fragments Cell biology 030104 developmental biology medicine.anatomical_structure Neuroprotective Agents Docosahexaenoic acid 030220 oncology & carcinogenesis Receptor-Interacting Protein Serine-Threonine Kinases Cytokines lipids (amino acids peptides and proteins) Aβ25-35 Therapeutics. Pharmacology Signal transduction Inflammation Mediators Alzheimer’s disease Signal Transduction |
| Zdroj: | Biomedicine & Pharmacotherapy, Vol 126, Iss, Pp 110102-(2020) |
| ISSN: | 1950-6007 |
| Popis: | Monocytes play a crucial role in Alzheimer's disease (AD), and docosahexaenoic acid (DHA) has a neuroprotective effect for many neurodegenerative diseases. However, mechanisms that regulate monocyte and Aβ protein interaction in AD and the effects of DHA on monocytes in the context of AD are not fully understood. The experiments were designed to further explore possible mechanisms of interaction between monocytes and Aβ plaques. Another objective of this study was to investigate a potential mechanism for Aβ-induced necroptosis involving the activation of MAPK and NF-kB signaling pathways in human THP-1 monocytes, as well as how these pathways might be modulated by DHA. Our findings indicate that Aβ25-35 has a "Hormesis" effect on cell viability and necroptosis in THP-1 cells, and Aβ25-35 influences THP-1 cells differentiation as analyzed by flow cytometry. Pretreatment of THP-1 monocytes with DHA effectively inhibited Aβ-induced activation and markedly suppressed protein expression of necroptosis (RIPK1, RIPK3, MLKL) and pro-inflammatory cytokines (TNF-α, IL-1β, IL-6). Moreover, our findings indicate that Aβ25-35 activated the ERK1/2 and p38 signaling pathways, but not NF-κB/p65 signaling, while pre-treatment with DHA followed by Aβ25-35 treatment suppressed only ERK1/2 signaling. Further study revealed that the expression level of RIPK3 is reduced much more during coadministration with DHA and necrostatin-1 (NEC-1) than administration alone with either of them, indicating that DHA may have additional targets. Meanwhile, this finding indicates that DHA can prevent Aβ-induced necroptosis of THP-1 cells via the RIPK1/RIPK3 signaling pathway. Our results also indicate that DHA treatment restored migration of THP-1 monocytes induced by Aβ25-35, and DHA treatment could be a promising new therapy for AD management. |
| Databáze: | OpenAIRE |
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