Mass spectrometric and computational analysis of cytokine-induced alterations in the astrocyte secretome

Sarah Dunn Keene, Todd M. Greco, Loannis Parastatidis, Seon Hwa Lee, Ethan G. Hughes, Rita J. Balice-Gordon, David W. Speicher, Harry Ischiropoulos

Research output: Contribution to journalArticle

52 Citations (Scopus)

Abstract

The roles of astrocytes in the CNS have been expanding beyond the long held view of providing passive, supportive functions. Recent evidence has identified roles in neuronal development, extracellular matrix maintenance, and response to inflammatory challenges. Therefore, insights into astrocyte secretion are critically important for understanding physiological responses and pathological mechanisms in CNS diseases. Primary astrocyte cultures were treated with inflammatory cytokines for either a short (1 day) or sustained (7 days) exposure. Increased interleukin-6 secretion, nitric oxide production, cyclooxygenase-2 activation, and nerve growth factor (NGF) secretion confirmed the astrocytic response to cytokine treatment. MS/MS analysis, computational prediction algorithms, and functional classification were used to compare the astrocyte protein secretome from control and cytokine-exposed cultures. In total, 169 secreted proteins were identified, including both classically and nonconventionally secreted proteins that comprised components of the extracellular matrix and enzymes involved in processing of glycoproteins and glycosaminoglycans. Twelve proteins were detected exclusively in the secretome from cytokine-treated astrocytes, including matrix metalloproteinase-3 (MMP-3) and members of the chemokine ligand family. This compilation of secreted proteins provides a framework for identifying factors that influence the biochemical environment of the nervous system, regulate development, construct extracellular matrices, and coordinate the nervous system response to inflammation.

Original languageEnglish
Pages (from-to)768-782
Number of pages15
JournalProteomics
Volume9
Issue number3
DOIs
Publication statusPublished - 2009 Feb 1
Externally publishedYes

Keywords

  • Astrocytes
  • Comparative proteomics
  • Cytokines
  • Development
  • Protein secretion

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology

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  • Cite this

    Keene, S. D., Greco, T. M., Parastatidis, L., Lee, S. H., Hughes, E. G., Balice-Gordon, R. J., Speicher, D. W., & Ischiropoulos, H. (2009). Mass spectrometric and computational analysis of cytokine-induced alterations in the astrocyte secretome. Proteomics, 9(3), 768-782. https://doi.org/10.1002/pmic.200800385