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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.