MARKED LONGEVITY OF HUMAN LUNG PARENCHYMAL ELASTIC FIBERS DEDUCED FROM PREVALENCE OF D-ASPARTATE AND NUCLEAR-WEAPONS RELATED RADIOCARBON
MARKED LONGEVITY OF HUMAN LUNG PARENCHYMAL ELASTIC FIBERS DEDUCED FROM PREVALENCE OF D-ASPARTATE AND NUCLEAR-WEAPONS RELATED RADIOCARBON
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DOI：
10.1172/jci115204
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发表时间：
1991-05-01
影响因子：
15.9
通讯作者：
CAMPBELL, EJ
中科院分区：
文献类型：
--
作者：
SHAPIRO, SD;ENDICOTT, SK;CAMPBELL, EJ
肺实质的正常结构和功能依赖于弹性纤维。无定形弹性蛋白在体外具有生物化学稳定性，可为肺实质提供代谢稳定的结构框架。为了测试弹性蛋白在正常人肺实质中的代谢稳定性，我们(A)通过测量天冬氨酸外消旋来估计自蛋白质合成以来所经过的时间，以及(B)通过测量与核武器相关的C-14的流行率来模拟弹性蛋白的周转。用新工艺从正常肺组织中分离纯化弹性蛋白，用气相色谱和加速器-质谱仪分别测定D-天冬氨酸和C-14的含量。D-天冬氨酸随年龄呈线性增加；K(Asp)(1.76×10(-3)yr-1)与先前在非常稳定的人体组织中发现的相似，表明肺实质弹性蛋白的年龄与受试者的年龄一致。放射性碳的流行数据也与弹性蛋白超常的代谢稳定性一致；计算出的弹性蛋白的平均碳滞留时间为74年(95%可信限，40-174年)。这些结果表明，“老化肺”的空隙扩大特征与肺实质弹性蛋白的新合成无关。本研究首次对人体细胞外基质成分的周转进行了组织特异性评估，并强调了弹性蛋白对维持正常肺结构的潜在重要性。最重要的是，本工作为直接评估肺(尤其是肺气肿)、血管组织和皮肤疾病的细胞外基质损伤和修复的策略提供了基础。
Normal structure and function of the lung parenchyma depend upon elastic fibers. Amorphous elastin is biochemically stable in vitro, and may provide a metabolically stable structural framework for the lung parenchyma. To test the metabolic stability of elastin in the normal human lung parenchyma, we have (a) estimated the time elapsed since the synthesis of the protein through measurement of aspartic acid racemization and (b) modeled the elastin turnover through measurement of the prevalence of nuclear weapons-related C-14. Elastin purified by a new technique from normal lung parenchyma was hydrolyzed; then the prevalences of D-aspartate and C-14 were measured by gas chromatography and accelerator-mass spectrometry, respectively. D-aspartate increased linearly with age; K(asp) (1.76 x 10(-3)yr-1) was similar to that previously found for extraordinarily stable human tissues, indicating that the age of lung parenchymal elastin corresponded with the age of the subject. Radiocarbon prevalence data also were consistent with extraordinary metabolic stability of elastin; the calculated mean carbon residence time in elastin was 74 yr (95% confidence limits, 40-174 yr). These results indicate that airspace enlargement characteristic of "aging lung" is not associated with appreciable new synthesis of lung parenchymal elastin. The present study provides the first tissue-specific evaluation of turnover of an extracellular matrix component in humans and underscores the potential importance of elastin for maintenance of normal lung structure. Most importantly, the present work provides a foundation for strategies to directly evaluate extracellular matrix injury and repair in diseases of lung (especially pulmonary emphysema), vascular tissue, and skin.