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10.1074/jbc.M114.592998

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suck abstract from ncbi


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pmid25172508
      J+Biol+Chem 2014 ; 289 (42 ): 29195-207
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  • In vitro amyloidogenic peptides of galectin-7: possible mechanism of amyloidogenesis of primary localized cutaneous amyloidosis #MMPMID25172508
  • Ono K ; Fujimoto E ; Fujimoto N ; Akiyama M ; Satoh T ; Maeda H ; Fujii N ; Tajima S
  • J Biol Chem 2014[Oct]; 289 (42 ): 29195-207 PMID25172508 show ga
  • 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 ?-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.
  • |Actins/metabolism [MESH]
  • |Amino Acid Sequence [MESH]
  • |Amyloid/*metabolism [MESH]
  • |Amyloidosis, Familial/*metabolism [MESH]
  • |Apoptosis [MESH]
  • |Galectins/*metabolism [MESH]
  • |Humans [MESH]
  • |Keratinocytes/metabolism [MESH]
  • |Keratins/metabolism [MESH]
  • |Molecular Sequence Data [MESH]
  • |Peptides/*metabolism [MESH]
  • |Protein Structure, Secondary [MESH]
  • |Recombinant Proteins/metabolism [MESH]
  • |Skin Diseases, Genetic/*metabolism [MESH]


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