Involvement of formyl-peptide-receptor-like-1 and phospholipase D in the internalization and signal transduction of amyloid beta 1-42 in glial cells
Brandenburg, LO; Konrad, M; Wruck, C; Koch, T; Pufe, T; Lucius, R
HERO ID
1071013
Reference Type
Journal Article
Year
2008
Language
English
PMID
| HERO ID | 1071013 |
|---|---|
| In Press | No |
| Year | 2008 |
| Title | Involvement of formyl-peptide-receptor-like-1 and phospholipase D in the internalization and signal transduction of amyloid beta 1-42 in glial cells |
| Authors | Brandenburg, LO; Konrad, M; Wruck, C; Koch, T; Pufe, T; Lucius, R |
| Journal | Neuroscience |
| Volume | 156 |
| Issue | 2 |
| Page Numbers | 266-276 |
| Abstract | Recent studies suggest that the formyl-peptide-receptor-like-1 (FPRL1) plays an essential role in the inflammatory responses of host defense mechanisms and neurodegenerative disorders such as Alzheimer's disease (AD). We therefore analyzed whether amyloid beta1-42 (Abeta1-42) 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 Abeta1-42 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 Abeta1-42-induced activation of FPRL1. We were able to show that Abeta1-42 is rapidly internalized via FPRL1 in astrocytes and microglia. PLD was additionally activated by Abeta1-42 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 Abeta1-42-induced endocytosis and FPRL1 receptor signaling. |
| Doi | 10.1016/j.neuroscience.2008.07.042 |
| Pmid | 18723082 |
| Is Certified Translation | No |
| Dupe Override | No |
| Is Public | Yes |
| Language Text | English |
| Is Qa | No |