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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
2
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pubmed:dateCreated |
1995-2-24
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pubmed:abstractText |
The amyloid beta protein (A beta) of Alzheimer disease (AD) is derived from the proteolytic processing of the amyloid precursor proteins (APP), which are considered type I transmembrane proteins. Production of A beta from a transmembrane precursor predicts a proteolytic cleavage within the lipid bilayer, a site relatively inaccessible to proteases. Here we show that incubation of a membrane fraction of PC12 cells at 37 degrees C results in the solubilization of an APP species which migrates on SDS-PAGE as full-length APP. The release of this full-length APP was pH-dependent with a peak of activity of pH 9.0. At this pH about 19% of the membrane APP was released from the active subcellular fraction. Under the same conditions other transmembrane proteins remained insoluble. Very little APP was solubilized at 4 degrees C. APP solubilization was specifically inhibited by the serine protease inhibitors aprotinin and pefabloc. Other protease inhibitors, including leupeptin and alpha 1-antitrypsin, had no effect. Several metal cations, including Ca++ and Zn++, also inhibited release of soluble full-length APP. Low levels of full-length APP were also detected in both the soluble fraction of PC12 cell extracts and in the media of PC12 cell cultures. These data suggest the involvement of a serine protease in the solubilization of membrane, full-length APP. The release of this APP could provide a soluble substrate for the proteolytic enzymes involved in the production of A beta.
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pubmed:grant |
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/4-(2-aminoethyl)benzenesulfonylfluor...,
http://linkedlifedata.com/resource/pubmed/chemical/Amyloid,
http://linkedlifedata.com/resource/pubmed/chemical/Aprotinin,
http://linkedlifedata.com/resource/pubmed/chemical/Calcium,
http://linkedlifedata.com/resource/pubmed/chemical/Culture Media, Conditioned,
http://linkedlifedata.com/resource/pubmed/chemical/Neoplasm Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Nerve Tissue Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Prions,
http://linkedlifedata.com/resource/pubmed/chemical/Protease Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Precursors,
http://linkedlifedata.com/resource/pubmed/chemical/Serine Endopeptidases,
http://linkedlifedata.com/resource/pubmed/chemical/Sulfones,
http://linkedlifedata.com/resource/pubmed/chemical/Zinc
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pubmed:status |
MEDLINE
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pubmed:month |
Oct
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pubmed:issn |
0360-4012
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
1
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pubmed:volume |
39
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
211-8
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pubmed:dateRevised |
2007-11-14
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pubmed:meshHeading |
pubmed-meshheading:7530778-Amyloid,
pubmed-meshheading:7530778-Animals,
pubmed-meshheading:7530778-Aprotinin,
pubmed-meshheading:7530778-Calcium,
pubmed-meshheading:7530778-Cell Membrane,
pubmed-meshheading:7530778-Culture Media, Conditioned,
pubmed-meshheading:7530778-Hydrogen-Ion Concentration,
pubmed-meshheading:7530778-Neoplasm Proteins,
pubmed-meshheading:7530778-Nerve Tissue Proteins,
pubmed-meshheading:7530778-PC12 Cells,
pubmed-meshheading:7530778-Prions,
pubmed-meshheading:7530778-Protease Inhibitors,
pubmed-meshheading:7530778-Protein Precursors,
pubmed-meshheading:7530778-Rats,
pubmed-meshheading:7530778-Serine Endopeptidases,
pubmed-meshheading:7530778-Solubility,
pubmed-meshheading:7530778-Sulfones,
pubmed-meshheading:7530778-Temperature,
pubmed-meshheading:7530778-Zinc
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pubmed:year |
1994
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pubmed:articleTitle |
Solubilization of full-length amyloid precursor proteins from PC12 cell membranes.
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pubmed:affiliation |
Mount Sinai School of Medicine, Department of Psychiatry, New York, New York.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.
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