Lysophosphatidic acid receptor activation affects the C13NJ microglia cell line proteome leading to alterations in glycolysis,motility, and cytoskeletal architecture |
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Authors: | Eva Bernhart Manfred Kollroser Gerald Rechberger Helga Reicher Akos Heinemann Petra Schratl Seth Hallström Andrea Wintersperger Christoph Nusshold Trevor DeVaney Klaus Zorn‐Pauly Roland Malli Wolfgang Graier Ernst Malle Wolfgang Sattler |
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Affiliation: | 1. Institute of Molecular Biology and Biochemistry, Medical University of Graz, Austria;2. Institute of Forensic Medicine, Medical University of Graz, Austria;3. Institute of Molecular Biosciences, Karl‐Franzens University, Graz, Austria;4. Institute of Experimental and Clinical Pharmacology, Medical University of Graz, Austria;5. Institute of Physiological Chemistry, Medical University of Graz, Austria;6. Institute of Biophysics, Medical University of Graz, Austria |
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Abstract: | Microglia, the immunocompetent cells of the CNS, are rapidly activated in response to injury and microglia migration towards and homing at damaged tissue plays a key role in CNS regeneration. Lysophosphatidic acid (LPA) is involved in signaling events evoking microglia responses through cognate G protein‐coupled receptors. Here we show that human immortalized C13NJ microglia express LPA receptor subtypes LPA1, LPA2, and LPA3 on mRNA and protein level. LPA activation of C13NJ cells induced Rho and extracellular signal‐regulated kinase activation and enhanced cellular ATP production. In addition, LPA induced process retraction, cell spreading, led to pronounced changes of the actin cytoskeleton and reduced cell motility, which could be reversed by inhibition of Rho activity. To get an indication about LPA‐induced global alterations in protein expression patterns a 2‐D DIGE/LC‐ESI‐MS proteomic approach was applied. On the proteome level the most prominent changes in response to LPA were observed for glycolytic enzymes and proteins regulating cell motility and/or cytoskeletal dynamics. The present findings suggest that naturally occurring LPA is a potent regulator of microglia biology. This might be of particular relevance in the pathophysiological context of neurodegenerative disorders where LPA concentrations can be significantly elevated in the CNS. |
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Keywords: | 2‐D DIGE Cell biology Lipids Migration MS Rho |
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