MCP-1-Induced Migration of NT2 Neuroprogenitor Cells Involving APP Signaling

    Authors

    E. G. Vrotsos;K. Sugaya

    Comments

    Authors: contact us about adding a copy of your work at STARS@ucf.edu

    Abbreviated Journal Title

    Cell. Mol. Neurobiol.

    Keywords

    MCP-1; APP; Migration; Chemoattractant; NT2; Neuroprogenitor cells; AMYLOID PRECURSOR PROTEIN; MONOCYTE CHEMOATTRACTANT PROTEIN-1; EXPERIMENTAL BRAIN-INJURY; NEURAL STEM-CELLS; TRANSDUCTION PATHWAYS; CHEMOKINE RECEPTORS; HUMAN NEURONS; NERVOUS-SYSTEM; ADULT BRAIN; MOUSE-BRAIN; Cell Biology; Neurosciences

    Abstract

    Neuroprogenitor cells are an important resource because of their great potential to replace damaged cells in the brain caused by trauma and disease. Studies have shown that when neuroprogenitor cells are transplanted into the brain they migrate towards damaged areas, suggesting that these areas express factors that recruit migrating cells. Generally, after neuronal injury, there is a neuroinflammatory response that results in increased chemokine production. In this present study, we demonstrate that monocyte chemoattractant protein-1 (MCP-1) significantly induces the migration of NT2 neuroprogenitor cells. Activation of intracellular cyclic adenosine monophosphate or protein kinase C with forskolin and phorbol 12-myristate 13-acetate, respectively, was able to completely abolish the MCP-1-induced migration. Contrarily, neither extracellular signal-regulated kinase nor p38 mitogen-activated protein kinase was required for NT2 cells to respond to MCP-1. Previously, we showed that amyloid precursor protein (APP) activity increases MCP-1 expression in NT2 cells. We now demonstrate that NT2 cells expressing APP can induce migration of other neuroprogenitor cells. Utilizing a MCP-1 neutralizing antibody, we discovered that APP-induced migration was not caused solely by increased MCP-1 production. Interestingly, APP-increased expression of several C-C chemokines: MCP-1, regulated upon activation, normal T-cell expressed, and secreted (RANTES), and macrophage inflammatory protein alpha (MIP-1 alpha). This demonstrates the unique role APP has in regulating chemokine production, which directly affects cell migration. Taken together, these data provides greater detail of the chemotactic factors and intracellular signaling that direct neuroprogenitor cell migration, allowing for better understanding of cell migration during transplantation.

    Journal Title

    Cellular and Molecular Neurobiology

    Volume

    29

    Issue/Number

    3

    Publication Date

    1-1-2009

    Document Type

    Article

    Language

    English

    First Page

    373

    Last Page

    381

    WOS Identifier

    WOS:000265575300009

    ISSN

    0272-4340

    Share

    COinS