title: In vitro amyloidogenic peptides of galectin-7: possible mechanism of amyloidogenesis of primary localized cutaneous amyloidosis.
abstract: Pathogenesis of primary localized cutaneous amyloidosis (PLCA) is unclear, but pathogenic relationship to keratinocyte apoptosis has been implicated. We have previously identified galectin-7, actin, and cytokeratins as the major constituents of PLCA. Determination of the amyloidogenetic potential of these proteins by thioflavin T (ThT) method demonstrated that galectin-7 molecule incubated at pH 2.0 was capable of binding to the dye, but failed to form amyloid fibrils. When a series of galectin-7 fragments containing β-strand peptides were prepared to compare their amyloidogenesis, Ser(31)-Gln(67) and Arg(120)-Phe(136) were aggregated to form amyloid fibrils at pH 2.0. The rates of aggregation of Ser(31)-Gln(67) and Arg(120)-Phe(136) were dose-dependent with maximal ThT levels after 3 and 48 h, respectively. Their synthetic analogs, Phe(33)-Lys(65) and Leu(121)-Arg(134), which are both putative tryptic peptides, showed comparable amyloidogenesis. The addition of sonicated fibrous form of Ser(31)-Gln(67) or Phe(33)-Lys(65) to monomeric Ser(31)-Gln(67) or Phe(33)-Lys(65) solution, respectively, resulted in an increased rate of aggregation and extension of amyloid fibrils. Amyloidogenic potentials of Ser(31)-Gln(67) and Phe(33)-Lys(65) were inhibited by actin and cytokeratin fragments, whereas those of Arg(120)-Phe(136) and Leu(121)-Arg(134) were enhanced in the presence of Gly(84)-Arg(113), a putative tryptic peptide of galectin-7. Degraded fragments of the galectin-7 molecule produced by limited trypsin digestion, formed amyloid fibrils after incubation at pH 2.0. These results suggest that the tryptic peptides of galectin-7 released at neutral pH, may lead to amyloid fibril formation of PLCA in the intracellular acidified conditions during keratinocyte apoptosis via regulation by the galectin-7 peptide as well as actin and cytokeratins.
authors.affiliation: From the Department of Dermatology, National Defense Medical College, 3-2 Namiki, Tokorozawa, Saitama 359-8513, Japan and drde998@ndmc.ac.jp.
authors.forename: Koji
authors.initials: K
authors.lastname: Ono
authors.affiliation: From the Department of Dermatology, National Defense Medical College, 3-2 Namiki, Tokorozawa, Saitama 359-8513, Japan and.
authors.forename: Eita
authors.initials: E
authors.lastname: Fujimoto
authors.affiliation: From the Department of Dermatology, National Defense Medical College, 3-2 Namiki, Tokorozawa, Saitama 359-8513, Japan and.
authors.forename: Norihiro
authors.initials: N
authors.lastname: Fujimoto
authors.affiliation: From the Department of Dermatology, National Defense Medical College, 3-2 Namiki, Tokorozawa, Saitama 359-8513, Japan and.
authors.forename: Minoru
authors.initials: M
authors.lastname: Akiyama
authors.affiliation: From the Department of Dermatology, National Defense Medical College, 3-2 Namiki, Tokorozawa, Saitama 359-8513, Japan and.
authors.forename: Takahiro
authors.initials: T
authors.lastname: Satoh
authors.affiliation: Research Reactor Institute, Kyoto University, Kumatori, Sennan, Osaka 590-0494, Japan.
authors.forename: Hiroki
authors.initials: H
authors.lastname: Maeda
authors.affiliation: Research Reactor Institute, Kyoto University, Kumatori, Sennan, Osaka 590-0494, Japan.
authors.forename: Noriko
authors.initials: N
authors.lastname: Fujii
authors.affiliation: From the Department of Dermatology, National Defense Medical College, 3-2 Namiki, Tokorozawa, Saitama 359-8513, Japan and.
authors.forename: Shingo
authors.initials: S
authors.lastname: Tajima
mesh_terms: D000199:Actins / Q000378:metabolism; D000595:Amino Acid Sequence; D000682:Amyloid / Q000378:metabolism*; D028226:Amyloidosis, Familial / Q000378:metabolism*; D017209:Apoptosis; D037161:Galectins / Q000378:metabolism*; D006801:Humans; D015603:Keratinocytes / Q000378:metabolism; D007633:Keratins / Q000378:metabolism; D008969:Molecular Sequence Data; D010455:Peptides / Q000378:metabolism*; D017433:Protein Structure, Secondary; D011994:Recombinant Proteins / Q000378:metabolism; D012873:Skin Diseases, Genetic / Q000378:metabolism*; D014357:Trypsin / Q000378:metabolism
chemical_list: D000199:Actins; D000682:Amyloid; D037161:Galectins; C092525:LGALS7 protein, human; D010455:Peptides; D011994:Recombinant Proteins; D007633:Keratins; D014357:Trypsin
keywords: Actin; Amyloid; Apoptosis; Galectin; Keratin; Keratinocyte; β-strand