Background: Apolipoprotein A-II (apoA-II), an apoprotein of serum high density lipoprotein, is the serum precursor of murine senile amyloid protein fibril. Three types of apoA-II protein variants (type A, B, and C) were found among inbred strains of mice. We reported the decreased concentration and the accelerated clearance of serum apoA-II with advancing age in the senescence-accelerated mouse-prone (SAM-P/1) mice, a strain with a high incidence of severe senile systemic amyloidosis and type C apoA-II.
Experimental design: Age-related changes in hepatic mRNA levels and rates of synthesis of apoA-II were investigated in SAM-P/1 and SAM-R/1, the latter of which has a low incidence of amyloidosis and type B apoA-II.
Results: At age 2 months, both strains had the same levels of hepatic apoA-II mRNA. However, in SAM-P/1 after age 4 months, we observed a remarkable age-associated decrease in apoA-II mRNA levels and the level at age 14 months was about 50% of that seen at age 2 months. On the other hand, in SAM-R/1, the level at age 17 months was still 77.4% of the level at age 2 months. No age-related decrease in mRNA levels of apoA-I, another major apolipoprotein of high density lipoprotein, was observed in either strain. Slight age-associated decreases in ApoE mRNA levels and age-associated changes in apoB mRNA levels were observed, with the same profiles for both strains. The rates of hepatic synthesis of apoA-II protein decreased significantly in SAM-P/1 and decreased slightly in SAM-R/1, with advancing age. The parallel changes observed between mRNA levels and rates of synthesis of apoA-II indicate that decrease in the rate of apoA-II synthesis reflects age-associated decreases in mRNA levels.
Conclusions: These findings suggest that the decreased concentration of serum apoA-II protein with advancing age may be caused by a decrease in the level of its mRNA.