Stone P J, Lucey E C, Snider G L, Franzblau C
Department of Biochemistry, Boston University School of Medicine, Massachusetts 02118, USA.
Proc Soc Exp Biol Med. 1997 May;215(1):94-101. doi: 10.3181/00379727-215-44118.
Desmosine (DES) and isodesmosine (IDES) concentration in the urine can be used as a noninvasive method of assessing degradation of mature elastin in normal and pathologic states. The present study was undertaken to determine the distribution of elastin among organs and tissues of normal hamsters, and to determine the turnover rates of two elastin-containing organs (lung, thoracic aorta) as a reflection of their contributions to DES and IDES excretion in the urine. Hamsters were metabolically labeled at 5 days of age with 14C-lysine and studied at 1.5, 4.5, 8, and 12 months of age. The aorta DES + IDES-associated radioactivity did not change significantly over the age span of 1.5-12 months. Lung DES + IDES-associated radioactivity decreased with a half-life of 420 days. Measurement of DES + IDES pools in other tissues, with relatively low concentrations of elastin, was carried out by the isotope dilution technique. At 12 months of age, the head and paws pool, skin, skeletal muscle, gastrointestinal tract, heart-liver-kidney-spleen pool, lungs, and thoracic aorta represented 37%, 28%, 13%, 11%, 6%, 4%, and 1%, respectively, of total body DES + IDES. The organs with the highest DES + IDES-specific radioactivity at 12 months were heart-liver-kidney-spleen, lung, and gastrointestinal tract, with 310, 217, and 217 dpm/nmol, respectively. Skin had the lowest specific radioactivity, with 90 dpm/nmol. The specific radioactivity of DES + IDES in urine was 62 dpm/nmol at 12 months, down from 251 dpm/nmol at 1.5 months. These data clearly indicate that non-lung tissues contain a high proportion of the total body DES + IDES and suggest that pathology in these other pools of DES + IDES could result in significant elevation of urinary DES + IDES. Nevertheless, the relatively high specific radioactivity of DES + IDES in lung elastin as compared with urine makes monitoring labeled urinary DES + IDES in this animal model a sensitive tool for assessing elastin degradation in experimental lung disease.
尿中异锁链素(DES)和异异锁链素(IDES)的浓度可作为一种非侵入性方法,用于评估正常和病理状态下成熟弹性蛋白的降解情况。本研究旨在确定正常仓鼠各器官和组织中弹性蛋白的分布,并确定两个含弹性蛋白器官(肺、胸主动脉)的周转率,以反映它们对尿中DES和IDES排泄的贡献。仓鼠在5日龄时用14C-赖氨酸进行代谢标记,并在1.5、4.5、8和12月龄时进行研究。在1.5至12个月的年龄跨度内,主动脉中与DES + IDES相关的放射性没有显著变化。肺中与DES + IDES相关的放射性以420天的半衰期下降。通过同位素稀释技术对其他弹性蛋白浓度相对较低的组织中的DES + IDES池进行了测量。在12月龄时,头部和爪子池、皮肤、骨骼肌、胃肠道、心-肝-肾-脾池、肺和胸主动脉分别占全身DES + IDES的37%、28%、13%、11%、6%、4%和1%。12个月时,DES + IDES比放射性最高的器官是心-肝-肾-脾、肺和胃肠道,分别为310、217和217 dpm/nmol。皮肤的比放射性最低,为90 dpm/nmol。12个月时尿中DES + IDES的比放射性为62 dpm/nmol,低于1.5个月时的251 dpm/nmol。这些数据清楚地表明,非肺组织在全身DES + IDES中占很大比例,并表明这些其他DES + IDES池的病变可能导致尿中DES + IDES显著升高。然而,与尿液相比,肺弹性蛋白中DES + IDES的比放射性相对较高,这使得在该动物模型中监测标记的尿中DES + IDES成为评估实验性肺病中弹性蛋白降解的敏感工具。