Expression of the APC tumor suppressor protein in oligodendroglia

Bhat, Ratan V.; Axt, Karen J.; Fosnaugh, Jennifer S.; Smith, Kelly J.; Johnson, Karen A.; Hill, David E.; Kinzler, Kenneth W.; Baraban, Jay M.

doi:10.1002/(sici)1098-1136(199606)17:2<169::aid-glia8>3.0.co;2-y

Cited by 234 publications

(116 citation statements)

References 30 publications

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“…The antibodies applied were antiadenomatous polyposis coli (APC; monoclonal mouse anti-recombinant APC, clone CC-1, diluted 1:50, Merck) for oligodendrocytes [8], anti-CD3 (polyclonal rabbit antihuman, diluted 1:1,000, Dako, Hamburg, Germany) for T lymphocytes, anti-CD45R/B220 (monoclonal rat antimouse biotinylated, clone RA3-6B2, diluted 1:1,000, BD Biosciences Pharmingen, Erembodegem, Belgium) for B lymphocytes, anti-CD107b (monoclonal rat anti-mouse biotinylated, clone M3/84, diluted 1:400, Serotec, Oxford, UK) for microglia/macrophages [1,34,65], anti-GFAP (polyclonal rabbit anti-cow, diluted 1:1,000, Dako) for astrocytes, anti-MBP (polyclonal rabbit anti-human, diluted 1:800, Chemicon Europe, Hofheim/Taunus, Germany) for myelin, and anti-TMEV (polyclonal rabbit anti-TMEV capsid protein VP1, diluted 1:2,000 [36]). In MMP-or mock-injected animals, the number of CD107b-, CD3-, CD45R-, APC-, and GFAP-positive cells per CCP was counted.…”

Section: Histology Immunohistology and Immunofluorescencementioning

confidence: 99%

Matrix metalloproteinase-12 deficiency ameliorates the clinical course and demyelination in Theiler’s murine encephalomyelitis

Hansmann¹,

Herder²,

Kalkuhl

et al. 2012

Acta Neuropathol

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Matrix metalloproteinases (MMPs) are a family of extracellular proteases involved in the pathogenesis of demyelinating diseases like multiple sclerosis (MS). The aim of the present study was to investigate whether MMPs induce direct myelin degradation, leukocyte infiltration, disruption of the blood-brain barrier (BBB), and/or extracellular matrix remodeling in the pathogenesis of Theiler's murine encephalomyelitis (TME), a virus-induced model of MS. During the demyelinating phase of TME, the highest transcriptional upregulation was detected for Mmp12, followed by Mmp3. Mmp12 (-/-) mice showed reduced demyelination, macrophage infiltration, and motor deficits compared with wild-type- and Mmp3 knock-out mice. However, BBB remained unaltered, and the amount of extracellular matrix deposition was similar in knock-out mice and wild-type mice. Furthermore, stereotaxic injection of activated MMP-3, -9, and -12 into the caudal cerebellar peduncle of adult mice induced a focally extensive primary demyelination prior to infiltration of inflammatory cells, as well as a reduction in the number of oligodendrocytes and a leakage of BBB. All these results demonstrate that MMP-12 plays an essential role in the pathogenesis of TME, most likely due to its primary myelin- or oligodendrocyte-toxic potential and its role in macrophage extravasation, whereas there was no sign of BBB damage or alterations to extracellular matrix remodeling/deposition. Thus, interrupting the MMP-12 cascade may be a relevant therapeutic approach for preventing chronic progressive demyelination.

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Section: Histology Immunohistology and Immunofluorescencementioning

confidence: 99%

Matrix metalloproteinase-12 deficiency ameliorates the clinical course and demyelination in Theiler’s murine encephalomyelitis

Hansmann¹,

Herder²,

Kalkuhl

et al. 2012

Acta Neuropathol

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“…On the contrary, those markers that do selectively label cells of the oligodendrocyte lineage in situ are often of limited use, because they preferentially label the cytoplasmic soma region or the cell nucleus but cannot delineate the structure of the entire oligodendrocyte lineage cell or its particular developmental stage. This is exemplified by both the widely used CC1-antibody (Bhat et al 1996) and the Olig-and Sox-families of transcription factors, both of which are essential for oligodendrocyte development, maturation and maintenance (Ligon et al 2006;Wegner and Stolt 2005). Therefore, additional versatile markers that allow for the recognition of defined OPC lineage stages would aid a better understanding of the oligodendrogenesis in the developing and adult CNS.…”

Section: Introductionmentioning

confidence: 99%

Novel conserved oligodendrocyte surface epitope identified by monoclonal antibody 4860

et al. 2009

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Oligodendrocytes are the myelinating cells of the central nervous system. They differentiate from oligodendrocyte precursor cells through several intermediate states that can be followed by characteristic morphological changes and the expression of marker molecules. However, most oligodendrocyte lineage markers demarcate either the precursor or the differentiated oligodendrocyte in restricted subcellular compartments. Here, we describe a novel marker of the oligodendrocyte lineage recognised by the monoclonal antibody clone 4860. It selectively labels the surfaces of differentiated oligodendrocytes in culture and clearly differs from other oligodendrocyte markers. Importantly, the 4860 epitope highlights developing white matter tracts in rodent and avian brains and thus represents a useful and conserved feature. The 4860 epitope is not associated with protein backbones as revealed by the related 487/L5 antibody. Furthermore, the epitope disappears upon lipid extraction from cryosections or inhibition of sphingolipid synthesis in cultured oligodendrocytes. Thus, we conclude that mAb 4860 represents a novel lipid-based oligodendrocyte marker.

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“…APC was primarily expressed in oligodendrocytes in control rat brains, as demonstrated in this study. Our observation was consistent with previous studies which reported that high APC mRNA and protein levels were expressed in oligodendrocytes of the normal adult rat [9,10], and after spinal cord injuries [24,25]. However, during the time course of KAinduced neuronal degeneration, APC was specifically expressed in non-oligodendroglia.…”

Section: Discussionmentioning

confidence: 99%

“…2a, e). These cells resembled oligodendrocytes because of their small size and distribution, as demonstrated by previous studies in the normal brain [10]. We performed APC immunohistochemistry for the rat brain treated with Na Phenytoin alone, and obtained a similar staining pattern to the normal brain (data not shown).…”

Section: Immunohistochemistrymentioning

confidence: 99%

“…Recent studies have demonstrated that high APC levels were expressed during the development of the rat central nervous system [9], and persisted in the adult rat brain [10]. Especially, the expression of APC in oligodendrocytes is possible that APC mutation contribute to regulation of the transition from proliferating precursor to quiescent oligodendrocyte [10].…”

Section: Introductionmentioning

confidence: 96%

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Expression of Adenomatous Polyposis Coli Protein in Reactive Astrocytes in Hippocampus of Kainic Acid-Induced Rat

et al. 2009

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The adenomatous polyposis coli gene (APC) was initially identified through its link to colon cancer. It is associated with the regulation of cell cycle progression, survival, and differentiation of normal tissues. Recent studies have demonstrated that APC is also expressed in the adult brain at high levels. However, its role in glial cells under pathological progression remains unclear. In this study, we evaluated the expression of APC and its association with beta-catenin signaling pathway, following the induction of an excitotoxic lesion by kainic acid (KA) injection, which cause pyramidal cell degeneration. APC was predominantly present in oligodendrocytes in the normal brain, but was specifically associated with activated astrocytes in the KA-treated brain. Our quantitative analysis revealed that APC significantly increased from 1 day post lesion (PI), reached peak values at 3 days PI, and decreased thereafter. The phospho-GSK3beta levels also showed similar spatiotemporal patterns while beta-catenin expression was reduced at 1 and then increasingly returned to normal levels at 3, 7 days PI. For the first time, our data demonstrate the injury-induced astrocytic changes in the levels of APC, GSK3beta, and beta-catenin in vivo, which may actively be participate in cell adhesion and in the signaling pathway regulating cell survivals during brain insults.

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Expression of the APC tumor suppressor protein in oligodendroglia

Cited by 234 publications

References 30 publications

Matrix metalloproteinase-12 deficiency ameliorates the clinical course and demyelination in Theiler’s murine encephalomyelitis

Matrix metalloproteinase-12 deficiency ameliorates the clinical course and demyelination in Theiler’s murine encephalomyelitis

Novel conserved oligodendrocyte surface epitope identified by monoclonal antibody 4860

Expression of Adenomatous Polyposis Coli Protein in Reactive Astrocytes in Hippocampus of Kainic Acid-Induced Rat

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