Amyloid β-protein precursor (APP) of cultured cells: Secretory and non-secretory forms of APP

Kametani, Fuyuki; Haga, Shukoh; Tanaka, Kunihito; Ishii, Tsuyoshi

doi:10.1016/0022-510x(90)90097-7

Cited by 17 publications

(6 citation statements)

References 31 publications

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“…A secretory role for APP is supported by several in vitro studies in which culture media from neuroblastoma or other cell types contain large APP fragments (Kametani et al, 1990;Oltersdorf et al, 1989;van Nostrand et al, 1989;Weidemann et al, 1989). A role as a cell surface receptor or cell adhesion molecule is not supported by our observed APP localization.…”

Section: Immunoelectron Microscopymentioning

confidence: 99%

“…Despite the wealth of information that has been accumulated regarding the nucleic acid biochemistry of the APP gene, the function of the product proteins remains a mystery. It has been suggested that they are receptors (Kang et al, 1987), growth factors (Whitson et al, 1989), protease inhibitors (Oltersdorf et al, 1989), or cell adhesion molecules (Schubert et al, 1989;Shivers et al, 1988;Kametani et al, 1990). The levels of expression of various APP mRNAs and metabolism of their products in Alzheimer and normal brain are still uncertain.…”

Section: Introductionmentioning

confidence: 99%

“…These segments correspond to residues 18-38 (T97), residues 527-540 (R36), residues 597-620 (1-24 of BAP) (R17), and residues 681-695 (R37) of the Kang et al (1987) APP695 sequence. Data have already been presented on the synthesis of R17, R36, and R37, the preparation of antibodies to them, the proteins recognized in extracts of cell cultures (Kametani et al, 1990) or unfixed brain tissue (Ishii et al, 1989a,b;Kametani et al, 1989), along with preliminary evidence of their immunohistochemical localization in cryostat cut fresh tissue (Ishii et al, 1989a,b). In this report, we describe further immu-…”

Section: Introductionmentioning

confidence: 99%

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Immunohistochemical localization of beta‐amyloid precursor protein sequences in Alzheimer and normal brain tissue by light and electron microscopy

McGeer

Akiyama

Kawamata

et al. 1992

J of Neuroscience Research

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Immunohistochemical staining with antibodies directed against four segments of the amyloid precursor protein (APP) was studied by light and electron microscopy in normal and Alzheimer (AD) brain tissue. The segments according to the Kang et al. sequence were: 18-38 (T97); 527-540 (R36); 597-620 (1-24 of beta-amyloid protein [BAP], R17); and 681-695 (R37) (Kang et al. [1987]: Nature 325:733-736). The antibodies recognized full length APP in Western blots of extracts of APP transfected cells. They stained cytoplasmic granules in some pyramidal neurons in normal appearing tissue from control and AD cases. In AD affected tissue, the antibodies to amino terminal sections of APP stained tangled neurons and neuropil threads, and intensely stained dystrophic neurites in senile plaques. By electron microscopy, this staining was localized to abnormal filaments. The antibody to the carboxy terminal segment failed to stain neurofibrillary tangles or neuropil threads; it did stain some neurites with globular swellings. It also stained globular and elongated deposits in senile plaque areas. The antibody against the BAP intensely stained extracellular material in senile plaques and diffuse deposits. By electron microscopy, the antibodies all stained intramicroglial deposits. Some of the extracellular and intracellular BAP-positive deposits were fibrillary. Communication between intramicroglial and extracellular fibrils was detected in plaque areas. These data suggest the following sequence of events. APP is normally concentrated in intraneuronal granules. In AD, it accumulates in damaged neuronal fibers. The amino terminal portion binds to abnormal neurofilaments. Major fragments of APP are phagocytosed and processed by microglia with the BAP portion being preserved. The preserved BAP is then extruded and accumulates in extracellular tissue.

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Section: Immunoelectron Microscopymentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Immunohistochemical localization of beta‐amyloid precursor protein sequences in Alzheimer and normal brain tissue by light and electron microscopy

McGeer

Akiyama

Kawamata

et al. 1992

J of Neuroscience Research

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“…These results were obtained by using nonneuronal cells. In addition, APP has been found to be processed differently among a host of cell lines (Kametani et al, 1990). The mechanisms of APP processing in neuronal cells remain unknown.…”

Section: Yankner Etmentioning

confidence: 99%

Increased Expression of β‐Amyloid Protein Precursor and Microtubule‐Associated Protein τ During the Differentiation of Murine Embryonal Carcinoma Cells

Fukuchi

Deeb

Kamino

et al. 1992

Journal of Neurochemistry

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Expression of the genes encoding the beta/A4 amyloid protein precursor (APP) and microtubule-associated protein tau was studied in an embryonal carcinoma cell line (P19) that differentiates in vitro into cholinergic neurons after treatment with retinoic acid. Expression of APP increased 34- (mRNA) and 50-fold (protein) during neuronal differentiation; APP-695 accounted for most of this increase. These remarkable increases in APP expression coincided with a proliferation of neuronal processes and with an increase in content of tau mRNA. Moreover, subsequent decreases in the levels of APP and tau mRNA coincided with the onset of the degeneration of the neuronal processes. Immunocytochemical staining suggested that greater than 85% of the P19-derived neurons are cholinergic and that APP is present in the neuronal processes and cell bodies. These results suggest that APP may play an important role in construction of neuronal networks and neuronal differentiation and also indicate that this embryonal carcinoma cell line provides an ideal model system to investigate biological functions of APP and the roles of APP and tau protein in development of Alzheimer's disease in cholinergic neurons.

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“…Cos-1 cells were cultured in Dulbecco's medium with foetal calf serum that had been deactivated by heating to 56°C.EA.hy926 (Waxman et al, 1994), Bul7 (Kametani et al, 1990), and C6 (Amberger et a!., 1994) cells were grown in supplemented Dulbecco's modified Eagle's medium. D384 cells (Balmforth et al, 1986) were maintained in a 1:1 culture medium of F-l0/Dulbecco's modified Eagle's medium.…”

Section: Culture Of Cell Linesmentioning

confidence: 99%

Expression of Endothelin‐Converting Enzyme in Both Neuroblastoma and Glial Cell Lines and Its Localization in Rat Hippocampus

Barnes

Walkden

Wilkinson

et al. 1997

Journal of Neurochemistry

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Endothelin-converting enzyme is a phosphoramidon-sensitive metalloprotease that cleaves big endothelin to the potent vasoconstrictor peptide, endothelin. The converting enzyme is expressed in endothelial cells in a variety of tissues and in some secretory cells. In the present study, phosphoramidon-sensitive endothelinconverting enzyme activity has been demonstrated by radioimmunoassay in the neuroblastoma cell line, SH-SY5Y, and in Bu17 and 06 glioma lines. The identity of the activity was confirmed by immunoblotting, revealing a polypeptide of '-~12OkDa in each of these lines, in D384 glioma cells, and in primary astrocytes. Immunofluorescence revealed the cell-surface location of endothelinconverting enzyme in the neuronal and glial cell lines and in primary astrocytes. Pretreatment of SH-SY5Y and Bul 7 cells with phosphoramidon resulted in an apparent concentration of the enzyme protein in an intracellular compartment. Immunoperoxidase-staining of rat brain sections located this metalloprotease to the pyramidal cells of the hippocampus. Endothelin-converting enzyme-i was revealed by in situ hybridisation in the neuronal and glial cell lines. Key Words: Endothelins-Metalloprotease-Neutral endopeptidase-Endothelin-converting enzyme-Phosphoramidon. J. Neurochem. 68, 570-577 (1997).The endothelin (El) peptide family was identified originally in endothelial cells (Yanagisawa et al., 1988), where they are synthesised from larger precur.-sor proteins, the preproendothelins (Masaki and Yanagisawa, 1992). The three isoforms, ET-1, ET-2, and ET-3, are also found in nonvascular tissues (Inoue et al., 1989). In the brain, the presence of ET-l and ET-3 has been demonstrated in endothelial, glial, and neuronal cells (MacCumber et al., 1990;Ehrenreich et al., 1991;Fuxe et al., 1991;Giaid et al., 1991), where they may have important roles as neuropeptides, and in the regulation of cerebral blood flow and astrocytic function (Barone et al., 1995). ETs also act as morphogens, for example, in the development of tissues derived from the neural crest (Baynash et al., 1994;Kurihara et al., 1994;Puffenberger et al., 1994).The generation of ETs from the intermediate big ET (Yanagisawa et al., 1988) involves a unique proteolytic processing event, catalysed by a phosphoramidonsensitive El-converting enzyme (ECE) (Opgenorth et al., 1992;Turner and Murphy, 1996). Iwo phosphoramidon-sensitive ECEs have been cloned, ECE-I (Ikura et al., 1994;Schmidt et al., 1994;Shimada et al., 1994Shimada et al., , 1995aXu et al., 1994) and ECE-2 (Emoto and Yanagisawa, 1995). ECE-1 is expressed more abundantly in all the tissues examined to date. ECE-1 and ECE-2 show an overall identity of 59% and are distinguished principally by their sensitivity to phosphoramidon, their pH optimum, and probably their subcellular localization (Emoto and Yanagisawa, 1995). Additional isoforms of ECE-1 (ECE-la and ECE-1/3), which differ only in their N-terminal tails generated by alternative splicing, have been detected in several species (Shimada et al., 1995b...

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Amyloid β-protein precursor (APP) of cultured cells: Secretory and non-secretory forms of APP

Cited by 17 publications

References 31 publications

Immunohistochemical localization of beta‐amyloid precursor protein sequences in Alzheimer and normal brain tissue by light and electron microscopy

Immunohistochemical localization of beta‐amyloid precursor protein sequences in Alzheimer and normal brain tissue by light and electron microscopy

Increased Expression of β‐Amyloid Protein Precursor and Microtubule‐Associated Protein τ During the Differentiation of Murine Embryonal Carcinoma Cells

Expression of Endothelin‐Converting Enzyme in Both Neuroblastoma and Glial Cell Lines and Its Localization in Rat Hippocampus

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