title: Altered production and proteolytic processing of brevican by transforming growth factor beta in cultured astrocytes.
abstract: Brevican, a proteoglycan of the lectican family, inhibits neurite outgrowth and may also stabilize synapses. Little is known about its expression or function in vitro. This study seeks to determine whether a brevican-containing matrix is present in neural cultures, and if so, how the production of brevican may be modulated. To accomplish this, the content of brevican and its proteolytic fragments were measured in primary cultures of neurons, astrocytes and microglia after treatment with cytokines. These experiments revealed that astrocytes and neurons express several isoforms of brevican, whereas microglia do not produce this proteoglycan. Cleavage fragments of brevican were found primarily in neuronal and astrocyte culture medium. ADAMTS4 (a disintegrin and metalloproteinase with thrombospondin motifs), a protease that selectively cleaves lecticans, was detected in cultures of neurons, astrocytes and microglia. When astrocytes were challenged with various cytokines, it was found that treatment with transforming growth factor beta (TGFbeta) resulted in a marked increase in intact brevican in the culture medium that was accompanied by a trend for a decrease in ADAMTS-generated fragments of brevican and apparent ADAMTS activity. Thus, TGFbeta may play a role in neuronal plasticity through its regulation of brevican and the activity of the ADAMTSs.
authors.affiliation: University of South Florida College of Medicine, Department of Pharmacology and Therapeutics, Tampa, Florida, USA.
authors.forename: Michelle G
authors.initials: MG
authors.lastname: Hamel
authors.forename: Joanne
authors.initials: J
authors.lastname: Mayer
authors.forename: Paul E
authors.initials: PE
authors.lastname: Gottschall
mesh_terms: D051722:ADAM Proteins; D000071121:ADAMTS4 Protein; D000818:Animals; D000831:Animals, Newborn; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism*; D001921:Brain / Q000254:growth & development / Q000378:metabolism; D058581:Brevican; D002352:Carrier Proteins / Q000187:drug effects / Q000378:metabolism*; D002450:Cell Communication / Q000187:drug effects / Q000502:physiology; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D011508:Chondroitin Sulfate Proteoglycans; D018920:Coculture Techniques; D005109:Extracellular Matrix / Q000187:drug effects / Q000378:metabolism*; D037181:Lectins, C-Type; D017628:Microglia / Q000187:drug effects / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000187:drug effects / Q000378:metabolism*; D016501:Neurites / Q000187:drug effects / Q000378:metabolism*; D009473:Neuronal Plasticity / Q000187:drug effects / Q000502:physiology; D010446:Peptide Fragments / Q000378:metabolism; D010447:Peptide Hydrolases / Q000378:metabolism; D011348:Procollagen N-Endopeptidase / Q000378:metabolism; D020033:Protein Isoforms / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D016212:Transforming Growth Factor beta / Q000378:metabolism* / Q000494:pharmacology; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology
chemical_list: D058581:Brevican; D002352:Carrier Proteins; D011508:Chondroitin Sulfate Proteoglycans; D037181:Lectins, C-Type; D009419:Nerve Tissue Proteins; D010446:Peptide Fragments; D020033:Protein Isoforms; D016212:Transforming Growth Factor beta; D010447:Peptide Hydrolases; D051722:ADAM Proteins; D011348:Procollagen N-Endopeptidase; D000071121:ADAMTS4 Protein