小鼠体内循环单链DNA清除的动力学及机制
Kinetics and mechanisms for removal of circulating single-stranded DNA in mice.
作者信息
Emlen W, Mannik M
出版信息
J Exp Med. 1978 Mar 1;147(3):684-99. doi: 10.1084/jem.147.3.684.
Abstract
Clearance of exogenous ssDNA from circulation was rapid and occurred primarily through the liver. With higher doses of single-stranded DNA (ssDNA), both liver uptake and whole blood clearance approached a maximum, enabling larger amounts of ssDNA to persist in the circulation. The large molecular weight material (precipitable ssDNA) which remained in circulation was rapidly cleaved to 20,000-30,000 mol wt fragments by endonucleases, at least some of which could be demonstrated in plasma in vitro. Mononucleotide breakdown products appeared rapidly in circulation with no lag phase, suggesting that exonuclease activity was not dependent upon prior phagocytosis. Since no exonuclease activity could be demonstrated in plasma in vitro, it was postulated that breakdown of ssDNA by exonucleases occurs on the surface of hepatocytes of Kupffer cells.
摘要
外源性单链DNA从循环系统中的清除速度很快，主要通过肝脏进行。使用较高剂量的单链DNA（ssDNA）时，肝脏摄取和全血清除率均接近最大值，使得大量的ssDNA能够在循环系统中持续存在。循环中残留的大分子物质（可沉淀的ssDNA）被核酸内切酶迅速切割成20,000 - 30,000分子量的片段，其中至少一些片段在体外血浆中可以检测到。单核苷酸分解产物在循环中迅速出现，没有延迟期，这表明外切核酸酶活性不依赖于先前的吞噬作用。由于在体外血浆中未检测到外切核酸酶活性，因此推测外切核酸酶对ssDNA的分解发生在库普弗细胞的肝细胞表面。
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