Accumulation of pro-apolipoprotein A-II in mouse senile amyloid fibrils.
Apolipoprotein A-II (apoA-II), the major apoprotein of serum high-density lipoprotein, is deposited as amyloid fibrils (AApoAII) in murine senile amyloidosis. We have identified and purified a more basic amyloid protein from old-mouse liver. N-terminal sequencing of the protein revealed that the pro-segment of five amino acid residues (Ala-Leu-Val-Lys-Arg) extended from the N-terminal glutamine residue of mature apoA-II protein. MS analysis revealed the deposit of intact pro-apoA-II protein (molecular mass 9319 Da). Antiserum was prepared for staining of the AApoAII amyloid deposition. The relative abundance of pro-apoA-II to mature apoA-II in the amyloid-fibril fraction isolated from livers of mice with severe amyloidosis was 14.1%. The similar abundance of pro-apoA-II in the amyloid fibril fraction from the spleen (16.3%) suggested that deposited pro-apoA-II originated from the blood. The concentration of pro-apoA-II was much lower in the serum (1.5% of mature apoA-II) than in the amyloid-fibril fraction. There was no difference in the content of pro-apoA-II between the amyloidogenetic R1.P1-Apoa2c and amyloid-resistant SAMR1 strains at the age of 3 months. The abundance of pro-apoA-II in the amyloid-fibril fraction compared with the serum suggested that it plays a key role in the initialization of mouse senile amyloidosis.
Higuchi
K
K
Department of Senescence Biology, Chest Disease Research Institute, Kyoto University, Sakyo-ku, Kyoto 606, Japan.
Kogishi
K
K
Wang
J
J
Xia
C
C
Chiba
T
T
Matsushita
T
T
Hosokawa
M
M
D000595:Amino Acid Sequence; D000682:Amyloid / Q000378:metabolism*; D000686:Amyloidosis / Q000378:metabolism*; D000818:Animals; D016633:Apolipoprotein A-II / Q000737:chemistry / Q000378:metabolism*; D005260:Female; D007120:Immunochemistry; D013058:Mass Spectrometry; D051379:Mice; D008969:Molecular Sequence Data; D011498:Protein Precursors / Q000737:chemistry / Q000378:metabolism*
D000682:Amyloid; D016633:Apolipoprotein A-II; D011498:Protein Precursors