Arylsulfatase B regulates interaction of chondroitin-4-sulfate and kininogen in renal epithelial cells
Arylsulfatase B regulates interaction of chondroitin-4-sulfate and kininogen in renal epithelial cells
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DOI：
10.1016/j.bbadis.2010.01.014
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发表时间：
2010-05-01
影响因子：
6.2
通讯作者：
Tobacman, Joanne K.
中科院分区：
文献类型：
--
作者：
Bhattacharyya, Sumit;Kotlo, Kumar;Tobacman, Joanne K.
芳基硫酸酯酶B（N-乙酰半乳糖胺4-硫酸酯酶; AS B; ARSB）可从4-硫酸软骨素（C4 S; CSA）和硫酸皮肤素的非还原端去除4-硫酸酯基团，其细胞效应超出了与溶酶体贮积病粘多糖沉积症VI相关的效应。以前，与正常细胞相比，在囊性纤维化患者和组织培养中的恶性人乳腺上皮细胞系中报告了ASB活性降低。ASB沉默和过度表达与MCF-7细胞中syndecan-1和核心蛋白聚糖表达的改变以及人支气管上皮细胞中IL-8分泌的改变相关。在这份报告中，我们提出的作用，ASB在调节的激肽原缓激肽轴由于其对软骨素-4-硫酸化和相互作用的C4S与激肽原。在正常大鼠肾上皮细胞中，ASB在组织培养中的沉默或过表达改变了用过的培养基和细胞裂解物中总硫酸化糖胺聚糖（sGAG）、C4S、激肽原和缓激肽的含量。用软骨素酶ABC处理培养的细胞也增加了缓激肽分泌到用过的培养基中，并减少了C4S相关的激肽原。当ASB过表达时，与C4S相关的细胞激肽原下降，表明软骨素-4-硫酸化在调节激肽原-C4S相互作用中起重要作用。这些结果表明，ASB，由于其对软骨素-4-硫酸化的影响，可能会影响激肽原-缓激肽轴，从而可能会影响血压，因为ASB的活性受到几种离子，包括氯离子和磷酸盐，ASB的活动可能提供了盐的反应性和缓激肽相关的血压调节机制之间的联系。由爱思唯尔公司出版
The enzyme arylsulfatase B (N-acetylgalactosamine 4-sulfatase; ASB; ARSB), which removes 4-sulfate groups from the nonreducing end of chondroitin-4-sulfate (C4S;CSA) and dermatan sulfate, has cellular effects, beyond those associated with the lysosomal storage disease mucopolysaccharidosis VI. Previously, reduced ASB activity was reported in cystic fibrosis patients and in malignant human mammary epithelial cell lines in tissue culture compared to normal cells. ASB silencing and overexpression were associated with alterations in syndecan-1 and decorin expression in MCF-7 cells and in IL-8 secretion in human bronchial epithelial cells. In this report, we present the role of ASB in the regulation of the kininogen-bradykinin axis owing to its effect on chondroitin-4-sulfation and the interaction of C4S with kininogen. Silencing or overexpression of ASB in normal rat kidney epithelial cells in tissue culture modified the content of total sulfated glycosaminoglycans (sGAGs), C4S, kininogen, and bradykinin in spent media and cell lysates. Treatment of the cultured cells with chondroitinase ABC also increased the secretion of bradykinin into the spent media and reduced the C4S-associated kininogen. When ASB was overexpressed, the cellular kininogen that associated with C4S declined, suggesting a vital role for chondroitin-4-sulfation in regulating the kininogen-C4S interaction. These findings suggest that ASB, owing to its effect on chondroitin-4-sulfation, may impact on the kininogen-bradykinin axis and, thereby, may influence blood pressure.Because ASB activity is influenced by several ions, including chloride and phosphate, ASB activity may provide a link between salt responsiveness and the bradykinin-associated mechanism of blood pressure regulation. Published by Elsevier B.V.