Department of Biochemistry and Nutrition, Central Food Technological Research Institute, Mysore, Karnataka, India.
Glycobiology. 2011 Jul;21(7):960-72. doi: 10.1093/glycob/cwr029. Epub 2011 Mar 15.
Chondroitin sulfate (CS)/dermatan sulfate (DS) is a group of sulfated polymers, which play an essential role in various biological phenomena. In the kidney, they are present in small but significant amounts. Studies on their structure-function relationship in the kidney and their changes during diabetic conditions have not been rigorously looked into, which is the focus of this paper. The CS/DS content decreased significantly (14%) during diabetic conditions. This was accompanied by a decrease in the CS/heparan sulfate ratio. Disaccharide composition analysis revealed fine structural changes especially with respect to the E unit [glucuronic acid β1-3 N-acetyl d-galactosamine (4,6-O-sulfate)] and the degree of sulfation. The mRNA expression levels of major enzymes involved in the synthesis of the "E"-disaccharide unit showed a decrease during diabetes. The changes in CS/DS had implications on ligand-binding properties when tested in vitro for binding to major extracellular matrix (ECM) components such as type IV collagen, laminin and fibronectin. Thus, this study provides insights into the structure-function relationship of CS/DS in the kidney during diabetes and alterations of which could aggravate conditions such as diabetic nephropathy by virtue of them being a part of ECM components.
硫酸软骨素(CS)/硫酸皮肤素(DS)是一组硫酸化聚合物,在各种生物现象中起着重要作用。在肾脏中,它们的含量虽然很小,但却具有重要意义。关于它们在肾脏中的结构-功能关系及其在糖尿病状态下的变化的研究尚未得到严格的研究,这是本文的重点。在糖尿病状态下,CS/DS 的含量显著下降(14%)。这伴随着 CS/硫酸乙酰肝素比的下降。二糖组成分析显示出精细的结构变化,特别是关于 E 单元[葡萄糖醛酸β1-3 N-乙酰半乳糖胺(4,6-O-硫酸)]和硫酸化程度。主要参与“E”二糖单元合成的酶的 mRNA 表达水平在糖尿病期间下降。CS/DS 的变化在体外测试时对配体结合特性有影响,例如与主要细胞外基质(ECM)成分如 IV 型胶原、层粘连蛋白和纤维连接蛋白的结合。因此,这项研究深入了解了糖尿病期间肾脏中 CS/DS 的结构-功能关系,其变化可能通过成为 ECM 成分的一部分而加重糖尿病肾病等疾病的状况。