Accumulation of pro-apolipoprotein A-II in mouse senile amyloid fibrils

K Higuchi1, K Kogishi, J Wang

  • 1Department of Senescence Biology, Chest Disease Research Institute, Kyoto University, Sakyo-ku, Kyoto 606, Japan.

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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