Thermodynamic study of transthyretin association (wild‐type and senile forms) with heparan sulfate proteoglycan: pH effect and implication of the reactive histidine residue

The tetramer destabilization of transthyretin into monomers and its fibrillation are phenomena leading to amyloid deposition. Heparan sulfate proteoglycan (HSPG) has been found in all amyloid deposits. A chromatographic approach was developed to compare binding parameters between wild‐type transthyretin (wtTTR) and an amyloidogenic transthyretin (sTTR). Results showed a greater affinity of sTTR for HSPG at pH 7.4 compared with wtTTR owing to the monomeric form of sTTR. Analysis of the thermodynamic parameters showed that van der Waals interactions were involved at the complex interface for both transthyretin forms. For sTTR, results from the plot representing the number of protons exchanged vs pH showed that the binding mechanism was pH‐dependent with a critical value at a pH 6.5. This observation was due to the protonation of a histidine residue as an imidazolium cation, which was not accessible when TTR was in its tetrameric structure. At pH >6.5, dehydration at the binding interface and several contacts between nonpolar groups of sTTR and HSPG were also coupled to binding for an optimal hydrogen‐bond network. At pH <6.5, the protonation of the His residue from sTTR monomer when pH decreased broke the hydrogen‐bond network, leading to its destabilization and thus producing slight conformational changes in the sTTR monomer structure. Copyright © 2014 John Wiley & Sons, Ltd.     

液体发酵云芝蛋白多糖的分离及其鉴定

放射诱变筛选出的高产云芝菌种用液体发酵法培养的菌丝体和发酵液经热水提取、乙醇沉淀、１万分子量截面超滤得到淡黄灰色粉末状云芝图丝体蛋白多糖和橙灰色状的发酵液蛋白多糖，菌丝体和发酵液蛋白多糖的糖含量，蛋白质含量分别为６２．４％、２３．５％，与４３．８％、２７．１％。与日本商品云芝蛋白多糖（ＰＳ－Ｄ（相比较，发酵云芝菌丝体蛋白多糖在红外、紫外吸收，物理常数、单糖和氨基酸的组成上是一致，后者在纯度上则高于     

Toward a Constitutive Law of Cartilage: A Polymer Physics Perspective

To describe load bearing and lubrication of cartilage requires treating its collagen network and proteoglycan (PG) phases separately in a constitutive law of the tissue. We propose a framework for developing such an empirical constitutive law that treats the cartilage extracellular matrix (ECM) as a composite medium, with a PG phase that exerts a swelling pressure, and a collagen network phase that restrains it. We compare and contrast this model to a biomechanical constitutive law that aggregates the collagen and PG phases into a single “solid-like” elastic tissue matrix, and show that aggregation obscures essential differences in the physical-chemical properties of the collagen and PG constituents as well as their distinct biological roles within cartilage's ECM. We also relate moduli in the aggregate constitutive model to quantities measured in an osmotic stress titration experiment.     

尿激酶型纤溶酶原激活物对关节软骨蛋白多糖的影响

观察尿激酶型纤溶酶原激活物（urokinase-type plasminogen activator,uPA）对关节软骨基质中蛋白多糖的影响.实验选择健康新西兰大白兔42只并随机分为实验组和对照组,实验组24只,对照组18只;实验组在右膝关节内注射uPA 0.4μg/0.2mL,对照组注射等容量的生理盐水,注射后在4周、8周、12周分批处死取兔软骨提取测定葡糖氨基聚糖（glycosaminoglycan,GAG）含量.结果显示,在不同时期,GAG的总含量均减少,这些改变随时间的延长而渐不明显.由此可知,尿激酶型纤溶酶原激活物能降解关节软骨蛋白多糖,进而导致关节软骨的破坏.