Age-associated decreases in the messenger ribonucleic acid level and the rate of synthesis of apolipoprotein A-II in murine senile amyloidosis.
Age-associated decreases in the messenger ribonucleic acid level and the rate of synthesis of apolipoprotein A-II in murine senile amyloidosis.
复制标题
小鼠老年淀粉样变性中信使核糖核酸水平和载脂蛋白 A-II 合成率与年龄相关的下降。
DOI：
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发表时间：
1994
期刊：
影响因子：
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通讯作者：
K. Higuchi
中科院分区：
文献类型：
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作者：
K. Kitagawa;H. Naiki;T. Takeda;K. Higuchi
背景
载脂蛋白A-II（apoA-II）是血清高密度脂蛋白的载脂蛋白，是小鼠老年淀粉样蛋白原纤维的血清前体。在近交系小鼠中发现了三种类型的apoA-II蛋白变体（A、B和C型）。我们报道了在加速衰老的小鼠倾向（SAM-P/1）小鼠中，血清apoA-II的浓度随着年龄的增长而降低和加速清除，SAM-P/1小鼠是一种严重的老年系统性淀粉样变性和C型apoA-II的高发病率品系。
实验设计
在SAM-P/1和SAM-R/1中研究了肝脏mRNA水平和apoA-II合成速率的变化，后者的淀粉样变性和B型apoA-II发生率较低。
结果
在2月龄时，两种品系的肝脏apoA-II mRNA水平相同。然而，在SAM-P/1 4个月后，我们观察到apoA-II mRNA水平显着的年龄相关性下降，14个月时的水平约为2个月时的50%。另一方面，在SAM-R/1中，17月龄时的水平仍为2月龄时水平的77.4%。没有年龄相关的apoA-I，另一个主要的载脂蛋白的高密度脂蛋白的mRNA水平的下降，观察到在任何菌株。观察到ApoE mRNA水平的轻微年龄相关性降低和apoB mRNA水平的年龄相关性变化，两种菌株的特征相同。随着年龄的增长，SAM-P/1大鼠肝脏apoA-Ⅱ蛋白合成率显著下降，SAM-R/1大鼠肝脏apoA-Ⅱ蛋白合成率略有下降。在mRNA水平和apoA-II合成速率之间观察到的平行变化表明，apoA-II合成速率的降低反映了与年龄相关的mRNA水平的降低。
结论
这些结果表明，血清apoA-II蛋白浓度随年龄增长而下降，可能是由于其mRNA水平下降所致。
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.