The Alzheimer Amyloid Precursor Proteoglycan (Appican) Is Present in Brain and Is Produced by Astrocytes but Not by Neurons in Primary Neural Cultures

Shioi, Junichi; Pangalos, Menelas N.; Ripellino, James A.; Vassilacopoulou, Dido; Mytilineou, Catherine; Margolis, Richard U.; Robakis, Nikolaos K.

doi:10.1074/jbc.270.20.11839

Cited by 61 publications

(40 citation statements)

References 42 publications

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“…47). APP, but not the APLP2, sequence was found in the core protein of our appican preparations from C6 cells following chondroitinase digestion (1).…”

Section: Resultsmentioning

confidence: 98%

“…In this context, it is noteworthy that the secreted form of appican contains a Kunitz type serine protease inhibitor sequence (1,4). An undefined rat mast cell tryptase (67) has been reported to be a target for the Kunitz type serine protease inhibitor-containing APP.…”

Section: Discussionmentioning

confidence: 99%

“…Our study shows that CS-E is expressed in glioma C6 cells. Astrocytes are the only producers of appican among other brain cells (5) and are related to C6 cells. Therefore, we suggest that astrocytes also produce CS-E-containing appican.…”

Section: Discussionmentioning

confidence: 99%

“…Materials-Appican was purified essentially as described in our previous report (1). Briefly, rat C6 glioma cells transfected with the L-APP cDNA (6) were grown in Dulbecco's modified Eagle's medium with supplements.…”

Section: Methodsmentioning

confidence: 99%

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Appican, the Proteoglycan Form of the Amyloid Precursor Protein, Contains Chondroitin Sulfate E in the Repeating Disaccharide Region and 4-O-Sulfated Galactose in the Linkage Region

Tsuchida

Shioi²,

Yamada³

et al. 2001

Journal of Biological Chemistry

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Chondroitin sulfate (CS)-D and CS-E, which are characterized by oversulfated disaccharide units, have been shown to regulate neuronal adhesion, cell migration, and neurite outgrowth. CS proteoglycans (CSPGs) consist of a core protein to which one or more CS chains are attached via a serine residue. Although several brain CSPGs, including mouse DSD-1-PG/phosphacan, have been found to contain the oversulfated D disaccharide motif, no brain CSPG has been reported to contain the oversulfated E motif. Here we analyzed the CS chain of appican, the CSPG form of the Alzheimer's amyloid precursor protein. Appican is expressed almost exclusively by astrocytes and has been reported to have brain-and astrocyte-specific functions including stimulation of both neural cell adhesion and neurite outgrowth. The present findings show that the CS chain of appican has a molecular mass of 25-50 kDa. This chain contains a significant fraction (14.3%) of the oversulfated E motif GlcUA␤1-3GalNAc(4,6-O-disulfate). The rest of the chain consists of GlcUA␤1-3GalNAc(4-O-sulfate) (81.2%) and minor fractions of GlcUA␤1-3GalNAc and GlcUA␤1-3GalNAc(6-O-sulfate). We also show that the CS chain of appican contains in its linkage region the 4-O-sulfated Gal structure. Thus, appican is the first example of a specific brain CSPG that contains the E disaccharide unit in its sugar backbone and the 4-O-sulfated Gal residue in its linkage region. The presence of the E unit is consistent with and may explain the neurotrophic activities of appican.

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“…47). APP, but not the APLP2, sequence was found in the core protein of our appican preparations from C6 cells following chondroitinase digestion (1).…”

Section: Resultsmentioning

confidence: 98%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

See 2 more Smart Citations

Appican, the Proteoglycan Form of the Amyloid Precursor Protein, Contains Chondroitin Sulfate E in the Repeating Disaccharide Region and 4-O-Sulfated Galactose in the Linkage Region

Tsuchida

Shioi²,

Yamada³

et al. 2001

Journal of Biological Chemistry

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“…The in vitro calcification of primary mouse (20,21), human (22,23) and bovine (4,(24)(25)(26) VSMCs are commonly utilised models of vascular calcification. Cells derived from transgenic mouse models with vascular calcification phenotypes are also frequently studied (7,18,27).…”

Section: Introductionmentioning

confidence: 99%

MOVAS-1 cell line: A new in vitro model of vascular calcification

Mackenzie

Zhu²,

Longley³

et al. 2011

Int J Mol Med

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Abstract. Vascular calcification has severe clinical consequences in a number of diseases, including diabetes, atherosclerosis and end-stage renal disease. The in vitro calcification of primary mouse, human and bovine vascular smooth muscle cells (VSMCs) is commonly employed to examine the mechanisms of vascular calcification. However, to date, no published studies have utilised a murine cell line to investigate this process. In the present study, we aimed to determine whether the mouse VSMC line MOVAS-1 can calcify in vitro. We established that the calcification of MOVAS-1 cells can be induced in the presence of calcifying medium (containing β-glycerophosphate and ascorbic acid), as detected by Alizarin Red and von Kossa staining, and quantification of calcium deposition and alkaline phosphatase activity. We also showed that the time course of MOVAS-1 calcification is comparable to that of the primary murine aortic VSMCs, establishing the MOVAS-1 cells as a feasible and relevant model. Significant increases in the mRNA expression profile of key genes associated with vascular calcification (Ocn, Akp2 and PiT-1) were observed in MOVAS-1 cells cultured under calcifying conditions, with similar changes in expression in murine aortic VSMCs. Furthermore, a significant reduction in calcification was observed in MOVAS-1 cells following treatment with levamisole and etidronate, known inhibitors of calcification. In conclusion, we demonstrated that the MOVAS-1 line is a reliable, convenient and economical system in which to investigate vascular calcification in vitro, and will make a useful contribution to increasing our understanding of this pathological process.

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Identification and neuron specific expression of the S182/presenilin I protein in human and rodent brains

Elder

Tezapsidis

Carter

et al. 1996

J of Neuroscience Research

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The Alzheimer Amyloid Precursor Proteoglycan (Appican) Is Present in Brain and Is Produced by Astrocytes but Not by Neurons in Primary Neural Cultures

Cited by 61 publications

References 42 publications

Appican, the Proteoglycan Form of the Amyloid Precursor Protein, Contains Chondroitin Sulfate E in the Repeating Disaccharide Region and 4-O-Sulfated Galactose in the Linkage Region

Appican, the Proteoglycan Form of the Amyloid Precursor Protein, Contains Chondroitin Sulfate E in the Repeating Disaccharide Region and 4-O-Sulfated Galactose in the Linkage Region

MOVAS-1 cell line: A new in vitro model of vascular calcification

Identification and neuron specific expression of the S182/presenilin I protein in human and rodent brains

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