title: Presenilin 1 cleavage is a universal event in human organs.
abstract: A panel of antibodies raised against various regions of human presenilin 1(PS1)--the amino-terminal domain, the domain between the transmembrane domains 1 and 2, the cleavage-site, loop domains, or carboxyl-terminal domain--was prepared to analyze PS1 in human tissues. We observed the predominance of two fragments (28-kDa NH2 and 18-kDa COOH fragments) in various tissues, including cerebral cortices. In addition to these two fragments, we found a previously unidentified amino-terminal fragment of PS1 with Mr 14 kDa in the lungs, spleen, pancreas, and testes. Using a sensitive ELISA for PS1, we measured the amount of PS1 species in tissues and found high contents of PS1 fragment in the testes. Our data show that common and unique processing pathways of PS1 occur in a tissue-dependent manner. It is likely that cleavage at the loop structure of PS1 to produce a functional form is a common event in human organs.
authors.affiliation: Department of Molecular Biology, Tokyo Institute of Psychiatry, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Okochi
authors.forename: N
authors.initials: N
authors.lastname: Sahara
authors.forename: F
authors.initials: F
authors.lastname: Kametani
authors.forename: M
authors.initials: M
authors.lastname: Usami
authors.forename: T
authors.initials: T
authors.lastname: Arai
authors.forename: K
authors.initials: K
authors.lastname: Tanaka
authors.forename: K
authors.initials: K
authors.lastname: Ishii
authors.forename: A
authors.initials: A
authors.lastname: Yamamoto
authors.forename: H
authors.initials: H
authors.lastname: Mori
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism*; D000595:Amino Acid Sequence; D000911:Antibodies, Monoclonal / Q000276:immunology; D000918:Antibody Specificity; D015153:Blotting, Western; D001921:Brain / Q000254:growth & development*; D001923:Brain Chemistry / Q000502:physiology*; D002460:Cell Line; D002540:Cerebral Cortex / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D008565:Membrane Proteins / Q000378:metabolism*; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000378:metabolism; D011233:Precipitin Tests; D053764:Presenilin-1
chemical_list: D000911:Antibodies, Monoclonal; D008565:Membrane Proteins; C508853:PSEN1 protein, human; D010446:Peptide Fragments; D053764:Presenilin-1