Biosynthesis of collagen crosslinks. II. In vivo labelling and stability of lung collagen in rats.
Biosynthesis of collagen crosslinks. II. In vivo labelling and stability of lung collagen in rats.
复制标题
胶原交联的生物合成。
DOI：
10.1016/s0304-4165(89)80032-7
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发表时间：
1989
期刊：
影响因子：
--
通讯作者：
Reiser,KM
中科院分区：
文献类型：
--
作者：
Last,JA;Summers,P;Reiser,KM
在肺发育的几个关键时间点：第11天（肺泡增生）、第26天（平衡生长开始）、第42天（平衡生长结束）和第100天（存在成年肺结构），通过单次腹腔注射[3H]赖氨酸在体内标记大鼠肺胶原。测定了标记的羟基赖氨酸和双官能、希夫碱衍生的交联羟基赖氨酸氨基亮氨酸（HLNL）和二羟基赖氨酸氨基亮氨酸（DHLNL）的沉积速率。我们还测量了这些动物的三功能成熟交联羟基吡啶（OHP）的总肺含量。虽然在注射标记前体的不同时间，标记胶原[3H]羟赖氨酸的相对积累率相差约6倍，但在所研究的所有肺发育阶段，胶原交联的定量和定性模式非常相似。此外，根据标记交联的存在，肺胶原蛋白池很少或没有分解；无论注射放射性前体的大鼠年龄如何，肺DHLNL含量的变化完全可以通过其成熟到OHP来解释。我们得出的结论是，大鼠肺中成熟的交联胶原蛋白，这是一个必要的细胞外池，并没有以可测量的速度降解。因此，其他研究表明，使用不同方法在全动物肺中新合成的胶原蛋白的分解率明显较高，这可能不能反映肺总胶原蛋白的代谢命运，而可能表明正常肺胶原蛋白的降解主要或完全发生在细胞内。
Rat lung collagen was labelled in vivo by a single intraperitoneal injection of [3H]lysine at several key timepoints in lung development: days 11 (alveolar proliferation), 26 (start of equilibrated growth), 42 (end of equilibrated growth), and 100 (adult lung structure present). The rates of deposition of labelled hydroxylysine and the difunctional, Schiff base-derived crosslinks hydroxylysinonorleucine (HLNL) and dihydroxylysinonorleucine (DHLNL) were quantified. We also measured total lung content of the trifunctional, mature crosslink hydroxypyridinium (OHP) in these same animals. While the relative rates of accumulation of labelled collagen [3H]hydroxylysine differed by a factor of about 6 at the different times of injection of labelled precursor, quantitative and qualitative patterns of collagen crosslinking were very similar at all of the lung developmental stages studied. Furthermore, there was little or no breakdown of the lung collagen pool as defined by the presence of labelled crosslinks; changes in lung DHLNL content could be completely accounted for by its maturation to OHP, regardless of the age of the rats when injected with the radioactive precursor. We conclude that mature, crosslinked collagen in the lungs of rats, which is obligatorily an extracellular pool, is not being degraded at a measurable rate. Therefore, studies of others that have shown apparent high rates of breakdown of newly synthesized collagen in lungs of whole animals using different methods are probably not reflective of the metabolic fate of total lung collagen, and may indicate that degradation of normal lung collagen occurs predominantly or exclusively intracellularly.