Opposing roles of ERK, p38 MAP kinases in FGF2-induced astroglial process extension

Department of Pathology, University of Virginia Health System, PO Box 800904, Charlottesville, VA 22908, USA.
Molecular and Cellular Neuroscience (Impact Factor: 3.84). 05/2005; 28(4):779-90. DOI: 10.1016/j.mcn.2004.12.010
Source: PubMed


The stellate processes of astroglial cells undergo extensive remodeling in response to neural injury. Little is known about intracellular signaling mechanisms controlling process extension. We tested roles for the ERK and p38 MAP kinase pathways in a simplified culture model. FGF2-induced process extension was preceded by a strong and transient phosphorylation of ERK, and a modest activation of p38 MAP kinase, which exhibited significant basal activity. Phosphorylated ERK was found predominantly in the cytoplasm, whereas activated p38 MAP kinase was nuclear. Process extension was completely blocked by the specific MEK inhibitor U0126. Conversely, inhibition of the p38 MAP kinase pathway with SB202190 stimulated spontaneous process growth and greatly potentiated FGF2-induced process extension. The p38 inhibitor effect was reproduced with an adenovirus expressing dominant-negative p38 MAP kinase. Selective pharmacological blockade of MAP kinase pathways may enable modulation of the astroglial response to injury so as to promote neural regeneration.

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    • "Several growth factors have shown to trigger MAPKs in different cell models [27], [28], [29], [30], [37], [71], [72], [73], [74]. IGF-1 promoted phosphorylation of p38, ERK1/2 and JNKs, through which to induce expression of osterix in human mesenchymal stem cells [37]. "
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    PLoS ONE 08/2012; 7(8):e43383. DOI:10.1371/journal.pone.0043383 · 3.23 Impact Factor
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    • "Measuring cell dendricity was performed as previously described [54]. "
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    PLoS ONE 08/2012; 7(8):e41523. DOI:10.1371/journal.pone.0041523 · 3.23 Impact Factor
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    • "Actin dynamics and cell morphology have been shown to be regulated by several factors, including mitogen-activated protein kinases (MAPKs). For instance, the MEK inhibitor, U0126, blocks stellate process extension of fibroblast growth factor 2 (FGF2)-treated astroglia in vitro, while inhibition of the p38 MAPK pathway by SB202190 facilitate stellate process growth and extension of the same cells (Heffron and Mandell, 2005). The p38 MAPK cascade regulates actin polymerization in platelet-derived growth factor-induced cytoskeleton remodeling of aortic smooth muscle cells (Pichon et al., 2004). "
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    ABSTRACT: Cultured cortical primary astroglia treated with zinc died while rapidly detached from culture plates, a distinct part of zinc-treated astroglia. In the present study, we investigated the mechanism underlying the rapid change in the morphologic integrity of zinc-treated astroglia. Among the early cellular events occurring in zinc-treated astroglia, strong activation of p38 MAPK and JNK was evident. Although inhibitors of p38 (SB203580 and SB202190) or JNK (SP600125) did not protect zinc-insulted astroglia from cell death, the p38 inhibitors, but not the JNK inhibitor, suppressed actin filament and cell morphology disruption. The Ca(2+) ionophore, A23187, also suppressed actin filament and cell morphology disruption, but not cell death, of zinc-insulted astroglia. However, A23187 did not inhibit p38 MAPK activation in zinc-treated astroglia. Together these results suggest that zinc influx in astroglia results in rapid loss of the morphologic integrity via mechanisms regulated by p38 kinase and/or Ca(2+) signaling.
    03/2011; 20(1):45-53. DOI:10.5607/en.2011.20.1.45
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