Sulfated glycosaminoglycans (GAG) in the developing mouse brain. Quantitative aspects on the metabolism of total and individual sulfated GAG in vivo.
Sulfated glycosaminoglycans (GAG) in the developing mouse brain. Quantitative aspects on the metabolism of total and individual sulfated GAG in vivo.
复制标题
发育中的小鼠大脑中的硫酸化糖胺聚糖（GAG）。
DOI：
10.1016/0012-1606(87)90248-x
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发表时间：
1987
影响因子：
2.7
通讯作者：
U. Wiesmann
中科院分区：
文献类型：
--
作者：
T. Burkart;U. Wiesmann
通过用[35S]硫酸盐标记并在[35S]硫酸盐注射后24小时开始追踪，对发育中的小鼠大脑和小脑中总糖胺聚糖（GAG）以及硫酸软骨素（A+C）、硫酸皮肤素和硫酸乙酰肝素的硫酸化和脱硫进行定量。在发育中的大脑和小脑中，总硫酸化 GAG 的生物合成率在出生后不久（2 天）最高，此后急剧下降，并在 14 天后达到平台。硫酸软骨素和硫酸乙酰肝素的生物合成活性在14天内急剧下降，并在之后保持恒定水平。相比之下，硫酸皮肤素的生物合成速率增加长达 14 天。总硫酸化 GAG 以及硫酸软骨素、硫酸乙酰肝素和硫酸皮肤素的生物降解率与出生后 2 周内相应的生物合成率密切相关。总硫酸化 GAG 和单个硫酸化 GAG 均表现出较高的降解率，导致半衰期为数小时至 1·1·2 天。因此，硫酸化 GAG 过量合成，实际净含量似乎在很大程度上受到溶酶体降解的共同调节。在两个大脑部分中，观察到硫酸化 GAG 含量与总 GAG 含量成比例增加，从出生时的 40% 增加到 28 天时的 90%。由于在发育过程中，硫酸乙酰肝素和硫酸皮肤素除了硫酸软骨素减少外，还表现出其每日净合成量相对增加，因此证明了与 GAG 连接的硫酸根基团在发育过程中的增加。这种导致微环境变化的分子分化可能具有很高的功能意义。
Sulfation and desulfation of total glycosaminoglycans (GAG) as well as of chondroitin sulfates (A+ C), dermatan sulfate, and heparan sulfate were quantified in the developing cerebrum and cerebellum of mice by labeling with [35 S] sulfate combined with chases started 24 hr after [35 S] sulfate injection. In both the developing cerebrum and cerebellum, the rate of biosynthesis of total sulfated GAG was highest shortly after birth (2 days), decreased sharply thereafter, and reached a plateau after 14 days. The biosynthetic activities of chondroitin sulfates and heparan sulfate decreased sharply up to 14 days and retained constant levels afterward. By contrast, the rates of biosynthesis of dermatan sulfate increased up to 14 days. The biodegradation rates of total sulfated GAG as well as of chondroitin sulfates, heparan sulfate, and dermatan sulfate were strongly correlated with the corresponding rates of biosynthesis during the first 2 postnatal weeks. Total and individual sulfated GAG showed high degradation rates resulting in half-life times of a few hours up to 1 1 2 days. Thus sulfated GAG are synthesized in excess and the actual net content seems to be co-regulated to a high degree by lysosomal degradation. In both brain parts, a proportional increase of the sulfated GAG content vs the total GAG content from 40% at birth to 90% at 28 days was observed. Since during development heparan sulfate and dermatan sulfate manifested a relative increase in their daily net synthesis besides a decrease of chondroitin sulfates, a developmental increase of the sulfate groups linked to GAG is evidenced. This molecular differentiation resulting in microenvironmental changes may be of high functional significance.