期刊
NEUROSCIENCE
卷 156, 期 2, 页码 266-276出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.neuroscience.2008.07.042
关键词
glial cell; amyloid beta 1-42; formyl peptide receptor; FPRL1; phospholipase d; endocytosis
资金
- Hensel Foundation (University of Kiel, Germany)
Recent studies suggest that the formyl-peptide-receptor-like-1 (FPRL1) plays an essential role in the inflammatory responses of host defense mechanisms and neuro-degenerative disorders such as Alzheimer's disease (AD). We therefore analyzed whether amyloid beta 1-42 (A beta 1-42) increased the activity of phospholipase D (PLD) via FPRL1, which is an enzyme involved in the secretion, endocytosis and receptor signaling. PLD activity was determined using a transphosphatidylation assay. The internalization of A beta 1-42 via FPRL1 was visualized using fluorescence microscopy and quantified by ELISA (Enzyme Linked Immunosorbent Assay). Determining receptor activity by extracellular-signal regulated kinases 1/2 (ERK1/2) phosphorylation and cAMP level measurement verified the A beta 1-42-induced activation of FPRL1. We were able to show that A beta 1-42 is rapidly internalized via FPRL1 in astrocytes and microglia. PLD was additionally activated by A beta 1-42 and via FPRL1 in rat glial cells. Furthermore, the ERK1/2 phosphorylation by FPRL1 agonists was dependent on the PLD product phosphatidic acid (PA). Together, these data suggest that PLD plays an important role in the regulation of A beta 1-42-induced endocytosis and FPRL1 receptor signaling. Published by Elsevier Ltd on behalf of IBRO.
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