Gressner A M, Vasel A
Mech Ageing Dev. 1985 Sep;31(3):307-27. doi: 10.1016/0047-6374(85)90097-1.
The synthesis of sulfated proteoglycans in late fetal (19th to 22nd day of intrauterine life), early postnatal, and adult liver tissue as well as in hepatocytes and their distribution in plasma membranes were studied. Overall proteoglycan production is enhanced two-fold in fetal as compared with adult liver tissue. In contrast to slices from adult liver, in which the synthesis of heparan [35S]-sulfate comprises more than 80% and chondroitin sulfate less than 5% of total glycosaminoglycans, chondroitin [35S]sulfate is the major type of glycosaminoglycans synthesized in fetal liver representing about 50% of total sulfated glycosaminoglycans. Thus, the synthesis of chondroitin sulfate is elevated nearly 30-fold in fetal liver as compared with the adult counterpart. Immediately after birth chondroitin sulfate formation decreases rapidly reaching adult levels between the 10th and 15th day of postnatal life. The production of heparan sulfate is almost unchanged during perinatal liver development due to a relatively low fractional synthesis of heparan [35S]sulfate in fetal liver. Hepatocytes were identified as the cell type responsible for elevated chondroitin sulfate production in fetal liver. Erythroblasts, which synthesize chondroitin sulfate, contribute less than 10% to total glycosaminoglycan synthesis in embryonic liver. Plasma membranes of adult liver contain exclusively heparan sulfate whereas in neonatal liver cell membranes 25% of labeled glycosaminoglycans is represented by chondroitin sulfate, a fraction which decreases rapidly after birth. In parallel to the postnatal shut down of chondroitin sulfate synthesis the activity of the UDPxylose:coreprotein xylosyltransferase (EC. 2.4.2.26) decreases from 4.8 +/- 0.5 dpm/h per microgram protein to 0.3 +/- 0.1 dpm/h per microgram protein suggesting a regulatory function of the enzyme for proteochondroitin sulfate synthesis in developing liver. The formation of both heparan sulfate and chondroitin sulfate is dependent on functioning protein synthesis, which indicates, together with double labeling experiments using [3H]serine and [14C]glucosamine as isotopic precursors, their synthesis as proteoglycans. The positive correlation (r = 0.949) between the incorporation of [3H]thymidine into DNA and chondroitin [35S]sulfate production supports the assumption of a cell growth promoting activity of chondroitin sulfate and points to a significant role of the glycosaminoglycan in the process of cellular proliferation and tissue differentiation.
研究了胎儿后期（子宫内生活的第19至22天）、出生早期及成年肝脏组织中硫酸化蛋白聚糖的合成情况，以及在肝细胞中的合成情况及其在质膜中的分布。与成年肝脏组织相比，胎儿肝脏组织中蛋白聚糖的总体产量提高了两倍。与成年肝脏切片不同，成年肝脏切片中硫酸乙酰肝素[35S] - 硫酸盐的合成占总糖胺聚糖的80%以上，硫酸软骨素不到5%，而硫酸软骨素[35S] - 硫酸盐是胎儿肝脏中合成的主要糖胺聚糖类型，约占总硫酸化糖胺聚糖的50%。因此，与成年肝脏相比，胎儿肝脏中硫酸软骨素的合成增加了近30倍。出生后，硫酸软骨素的形成迅速减少，在出生后第10至15天达到成年水平。由于胎儿肝脏中硫酸乙酰肝素[35S] - 硫酸盐的合成分数相对较低，硫酸乙酰肝素的产量在围产期肝脏发育过程中几乎没有变化。肝细胞被确定为胎儿肝脏中硫酸软骨素产量升高的细胞类型。合成硫酸软骨素的成红细胞对胚胎肝脏中总糖胺聚糖合成的贡献不到10%。成年肝脏的质膜仅含有硫酸乙酰肝素，而在新生儿肝脏细胞膜中，25%的标记糖胺聚糖由硫酸软骨素代表，这一比例在出生后迅速下降。与出生后硫酸软骨素合成的停止同时，UDP - 木糖：核心蛋白木糖基转移酶（EC. 2.4.2.26）的活性从每微克蛋白质4.8 +/- 0.5 dpm/h降至每微克蛋白质0.3 +/- 0.1 dpm/h，这表明该酶对发育中的肝脏中蛋白硫酸软骨素的合成具有调节作用。硫酸乙酰肝素和硫酸软骨素的形成均依赖于正常的蛋白质合成，这与使用[3H]丝氨酸和[14C]葡萄糖胺作为同位素前体的双重标记实验一起表明它们作为蛋白聚糖的合成。[3H]胸苷掺入DNA与硫酸软骨素[35S] - 硫酸盐产量之间的正相关（r = 0.949）支持了硫酸软骨素具有促进细胞生长活性的假设，并表明这种糖胺聚糖在细胞增殖和组织分化过程中起重要作用。
