[Show abstract][Hide abstract] ABSTRACT: N-acetylgalactosamine-4-sulfatase (Arylsulfatase B; ARSB) is the enzyme that removes sulfate groups from the N-acetylgalactosamine-4-sulfate residue at the non-reducing end of chondroitin-4-sulfate (C4S) and dermatan sulfate (DS). Previous studies demonstrated reduction in cell-bound high molecular weight kininogen in normal rat kidney (NRK) epithelial cells when chondroitin-4-sulfate content was reduced following overexpression of ARSB activity, and chondroitinase ABC produced similar decline in cell-bound kininogen. Reduction in the cell-bound kininogen was associated with increase in secreted bradykinin. In this report, we extend the in vitro findings to in vivo models, and present findings in Dahl salt-sensitive (SS) rats exposed to high (SSH) and low salt (SSL) diets. In the renal tissue of the SSH rats, ARSB activity was significantly less than in the SSL rats, and chondroitin-4-sulfate and total sulfated glycosaminoglycan content were significantly greater. Disaccharide analysis confirmed marked increase in C4S disaccharides in the renal tissue of the SSH rats. In contrast, unsulfated, hyaluronan-derived disaccharides were increased in the rats on the low salt diet. In the SSH rats, with lower ARSB activity and higher C4S levels, cell-bound, high-molecular weight kininogen was greater and urinary bradykinin was lower. ARSB activity in renal tissue and NRK cells declined when exogenous chloride concentration was increased in vitro. The impact of high chloride exposure in vivo on ARSB, chondroitin-4-sulfation, and C4S-kininogen binding provides a mechanism that links dietary salt intake with bradykinin secretion and may be a factor in blood pressure regulation.
[Show abstract][Hide abstract] ABSTRACT: Arylsulfatase B (N-acetylgalactosamine-4-sulfatase; ARSB) removes 4-sulfate groups from chondroitin-4-sulfate (C4S) and dermatan sulfate and is required for their degradation. In human prostate stromal and epithelial cells, when ARSB was silenced, C4S, versican and versican promoter activity increased, and the galectin-3 that co-immunoprecipitated with C4S declined. Galectin-3 silencing inhibited the ARSB-silencing-induced increases in versican and versican promoter due to effects on the AP-1-binding site in the versican promoter. These findings demonstrate for the first time the transcriptional mechanism whereby ARSB can regulate expression of an extracellular matrix proteoglycan with C4S attachments. In addition, following ARSB silencing, C4S that co-immunoprecipitated with versican increased, whereas co-immunoprecipitated EGFR declined, total EGFR increased and exogenous EGF-induced cell proliferation increased, suggesting profound effects of ARSB on vital cell processes.Oncogene advance online publication, 18 November 2013; doi:10.1038/onc.2013.483.
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