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Accumulation of pro-apolipoprotein A-II in mouse senile amyloid fibrils
1Department of Senescence Biology, Chest Disease Research Institute, Kyoto University, Sakyo-ku, Kyoto 606, Japan.
Abstract:
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.
Insights
A newly identified precursor form of Apolipoprotein A-II (pro-apoA-II) is deposited in amyloid fibrils, playing a crucial role in initiating mouse senile amyloidosis.
Area of Science:
- Biochemistry
- Molecular Biology
- Pathology
Background:
- Serum high-density lipoprotein contains Apolipoprotein A-II (apoA-II), a major apoprotein.
- ApoA-II is deposited as amyloid fibrils (AApoAII) in murine senile amyloidosis.
Purpose of the Study:
- To identify and characterize the amyloid protein deposited in old mouse liver.
- To investigate the role of precursor forms of apoA-II in amyloidosis.
Main Methods:
- Protein purification from old mouse liver.
- N-terminal sequencing and Mass Spectrometry (MS) analysis.
- Antiserum preparation for amyloid deposition staining.
Main Results:
- A more basic amyloid protein, intact pro-apoA-II (9319 Da), was identified and purified.
- Pro-apoA-II constituted 14.1% of the amyloid-fibril fraction in severe amyloidosis livers.
- Pro-apoA-II abundance in amyloid fibrils was significantly higher than in serum, suggesting a key role in amyloid initiation.
Conclusions:
- Pro-apoA-II is a significant component of AApoAII amyloid deposits in mice.
- The higher concentration of pro-apoA-II in amyloid fibrils compared to serum indicates its critical role in the initiation of mouse senile amyloidosis.
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