Brevican isoforms associate with neural membranes

Seidenbecher, Constanze I.; Smalla, Karl‐Heinz; Fischer, Nora; Gundelfinger, Eckart D.; Kreutz, Michael R.

doi:10.1046/j.1471-4159.2002.01183.x

Cited by 49 publications

(43 citation statements)

References 40 publications

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“…7 We show that in human glioblastomas and, to a lesser extent, in normal human brain brevican as well as the proteases responsible for its degradation are produced. This explains that part of the extracellular brevican is degraded, the lower amounts in normal brain even more.…”

Section: Discussionmentioning

confidence: 79%

“…HEK293 cells stably transfected with brevican vector pRC-CMV/359H, eukaryotic selection marker G418/neomycin, 7 were cultivated in DMEM with 10% FCS and 600 lg/ml G418/neomycin (Calbiochem, San Diego, CA). The human monocyte cell line THP-1, human dermal fibroblasts and human immortalized chondrocytes were obtained and cultivated as described.…”

Section: Cell Culture and Tissue Samplesmentioning

confidence: 99%

“…Tissue homogenates (aliquots with equal protein contents) were boiled and reduced in 50-200 ll SDS-PAGE sample buffer, proteins separated in NuPAGE pre-cast gel (NP0321, NuPAGE 4-12% Bis-Tris Gel, Invitrogen) or by 10% standard SDS-PAGE, transferred onto a polyvinylidene difluoride (PVDF) membranes that were blocked and incubated with anti-ADAMTS4 or 5 (C-terminal domains, rabbit polyclonal antibodies 1:250; Chemicon, Temecula, CA) or anti-brevican 7 (1:5,000) followed (after washings) by horseradish peroxidase-labeled anti-rabbit IgG (1:30,000; DAKO, Glostrup, Denmark). Bound antibody was visualized by enhanced chemiluminescence (ECL system; Amersham).…”

Section: Western Blotsmentioning

confidence: 99%

“…At 0 hr, 1 hr and 24 hr, 20 ll aliquots were withdrawn, boiled and reduced, separated by SDS-PAGE and Western blot obtained as above that were probed with anti-brevican (guinea pig or rabbit polyclonal antibodies, 1:20). 7 …”

Section: Analysis Of Brevican Degradationmentioning

confidence: 99%

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Matrix‐degrading proteases ADAMTS4 and ADAMTS5 (disintegrins and metalloproteinases with thrombospondin motifs 4 and 5) are expressed in human glioblastomas

Held‐Feindt

Paredes

Blömer

et al. 2005

Intl Journal of Cancer

128

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Brain tumors, in particular glioblastomas, have a high morbidity and mortality, mainly due to their invasive nature. A prerequisite for this invasiveness is cell migration based on increased expression of proteases digesting the extracellular matrix. Brevican, an important extracellular proteoglycan that is upregulated in glioblastomas, can be degraded by certain proteases. We demonstrate that in human glioblastomas secretory proteases like ADAMTS4 and ADAMTS5 (aggrecanases 1 and 2; ADAMTS 5 a disintegrin and metalloproteinase with thrombospondin motifs) are expressed on the mRNA and protein levels in considerable amounts. Realtime RT-PCR shows a higher levels of ADAMTS4 and 5 expressions in glioblastomas in situ, compared to cultured human glioblastoma cells. The upregulation of these proteases in vivo by cytokines may explain this difference. In vitro, transforming growth factor-b induces ADAMTS4, but less ADAMTS5, and interleukin1b ADAMTS5, but not ADAMTS4. As demonstrated by immunohistochemistry and confocal microscopy in situ, ADAMTS5 expression is confined to proliferating glioblastoma cells of surgical tumor sections and with lower intensity to astroglial cells in normal brain sections, as opposed to brevican. In vitro, glioblastoma-derived ADAMTS5 degrades recombinant human brevican to several smaller fragments. Our results show that ADAMTS4 and 5 are upregulated on proliferating glioblastoma cells and these proteases may contribute to their invasive potential. ' 2005 Wiley-Liss, Inc.Key words: glioblastoma; invasion; proteases; extracellular matrix; degradation; cytokines High-grade glial tumors (anaplastic astrocytoma and glioblastoma multiforme) are the most frequent brain tumors in adults. 1,2 Despite multimodal therapeutic efforts, the mean survival time is only 9-12 months for glioblastoma multiforme (WHO Grade IV) and 2 years for anaplastic astrocytoma (WHO Grade III). The ability of individual tumor cells to infiltrate brain tissue is the primary reason for this poor prognosis. Individual tumor cells (''guerrilla cells'') can migrate more than 4.0-7.0 cm from the gross tumor into the surrounding normal brain tissue. 3 In part, the migratory and invasive behavior is a consequence of tumor cell interaction with specific components of the extracellular matrix (ECM). Brain ECM components include laminin, collagen IV, tenascin, fibronectin and proteoglycans. 4 The glycosaminoglycan hyaluronic acid (HA) plays a central role in cellular proliferation, differentiation and migration, and may be a key element in tumor spreading. 5 BEHAB (brain enriched hyaluronan binding)/brevican is a recently identified HA binding protein that belongs to the lectican family. 6-9 BEHAB/brevican expression is developmentally regulated in the central nervous system, in particular during periods of glial cell proliferation and migration. 9 Accordingly, BEHAB/brevican is upregulated in the vast majority of surgical glioblastomas, 9-11 and expression levels and proteolytic cleavage of BEHAB/brevican seem to correlate with tumo...

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Section: Discussionmentioning

confidence: 79%

Section: Cell Culture and Tissue Samplesmentioning

confidence: 99%

Section: Western Blotsmentioning

confidence: 99%

Section: Analysis Of Brevican Degradationmentioning

confidence: 99%

See 2 more Smart Citations

Matrix‐degrading proteases ADAMTS4 and ADAMTS5 (disintegrins and metalloproteinases with thrombospondin motifs 4 and 5) are expressed in human glioblastomas

Held‐Feindt

Paredes

Blömer

et al. 2005

Intl Journal of Cancer

128

View full text Add to dashboard Cite

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“…Protein preparation and Western blotting were essentially performed as described previously (Seidenbecher et al, 2002), with minor modifications. Briefly, human brain tissue from the hippocampus (including dentate gyrus and CA1 and CA3 regions) and from the striatum was homogenized in TBS containing 1% Triton X-100 and a protease inhibitor cocktail (Complete; Boehringer Mannheim, Mannheim, Germany).…”

Section: Methodsmentioning

confidence: 99%

The Dopaminergic Midbrain Participates in Human Episodic Memory Formation: Evidence from Genetic Imaging

et al. 2006

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Recent data from animal studies raise the possibility that dopaminergic neuromodulation promotes the encoding of novel stimuli. We investigated a possible role for the dopaminergic midbrain in human episodic memory by measuring how polymorphisms in dopamine clearance pathways affect encoding-related brain activity (functional magnetic resonance imaging) in an episodic memory task. In 51 young, healthy adults, successful episodic encoding was associated with activation of the substantia nigra. This midbrain activation was modulated by a functional variable number of tandem repeat (VNTR) polymorphism in the dopamine transporter (DAT1) gene. Despite no differences in memory performance between genotype groups, carriers of the (low expressing) 9-repeat allele of the DAT1 VNTR showed relatively higher midbrain activation when compared with subjects homozygous for the 10-repeat allele, who express DAT1 at higher levels. The catechol-O-methyl transferase (COMT) Val108/158Met polymorphism, which is known to modulate enzyme activity, affected encoding-related activity in the right prefrontal cortex (PFC) and in occipital brain regions but not in the midbrain. Moreover, subjects homozygous for the (low activity) Met allele showed stronger functional coupling between the PFC and the hippocampus during encoding. Our finding that genetic variations in the dopamine clearance pathways affect encoding-related activation patterns in midbrain and PFC provides strong support for a role of dopaminergic neuromodulation in human episodic memory formation. It also supports the hypothesis of anatomically and functionally distinct roles for DAT1 and COMT in dopamine metabolism, with DAT1 modulating rapid, phasic midbrain activity and COMT being particularly involved in prefrontal dopamine clearance.

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Activity‐dependent formation and functions of chondroitin sulfate‐rich extracellular matrix of perineuronal nets

Dityatev

Brückner

Dityateva

et al. 2007

Developmental Neurobiology

324

307

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Extracellular matrix molecules--including chondroitin sulfate proteoglycans, hyaluronan, and tenascin-R--are enriched in perineuronal nets (PNs) associated with subsets of neurons in the brain and spinal cord. In the present study, we show that similar cell type-dependent extracellular matrix aggregates are formed in dissociated cell cultures prepared from early postnatal mouse hippocampus. Starting from the 5th day in culture, accumulations of lattice-like extracellular structures labeled with Wisteria floribunda agglutinin were detected at the cell surface of parvalbumin-expressing interneurons, which developed after 2-3 weeks into conspicuous PNs localized around synaptic contacts at somata and proximal dendrites, as well as around axon initial segments. Physiological recording and intracellular labeling of PN-expressing neurons revealed that these are large fast-spiking interneurons with morphological characteristics of basket cells. To study mechanisms of activity-dependent formation of PNs, we performed pharmacological analysis and found that blockade of action potentials, transmitter release, Ca2+ permeable AMPA subtype of glutamate receptors or L-type Ca2+ voltage-gated channels strongly decreased the extracellular accumulation of PN components in cultured neurons. Thus, we suggest that Ca2+ influx via AMPA receptors and L-type channels is necessary for activity-dependent formation of PNs. To study functions of chondroitin sulfate-rich PNs, we treated cultures with chondroitinase ABC that resulted in a prominent reduction of several major PN components. Removal of PNs did not affect the number and distribution of perisomatic GABAergic contacts but increased the excitability of interneurons in cultures, implicating the extracellular matrix of PNs in regulation of interneuronal activity.

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Brevican isoforms associate with neural membranes

Cited by 49 publications

References 40 publications

Matrix‐degrading proteases ADAMTS4 and ADAMTS5 (disintegrins and metalloproteinases with thrombospondin motifs 4 and 5) are expressed in human glioblastomas

Matrix‐degrading proteases ADAMTS4 and ADAMTS5 (disintegrins and metalloproteinases with thrombospondin motifs 4 and 5) are expressed in human glioblastomas

The Dopaminergic Midbrain Participates in Human Episodic Memory Formation: Evidence from Genetic Imaging

Activity‐dependent formation and functions of chondroitin sulfate‐rich extracellular matrix of perineuronal nets

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