Extra-Lysosomal Localization of Arylsulfatase B in Human Colonic Epithelium

Abstract

SummaryThe enzyme arylsulfatase B (N-acetylgalactosamine-4-sulfatase; ARSB; ASB) removes 4-sulfate groups from the sulfated glycosaminoglycans (sGAG) chondroitin-4-sulfate (C4S) and dermatan sulfate (DS). Inborn deficiency of ARSB leads to the lysosomal storage disease mucopolysaccharidosis VI, characterized by accumulation of sGAG in vital organs, disruption of normal physiological processes, severe morbidity, and premature death. Recent published work demonstrated extra-lysosomal localization with nuclear and cell membrane ARSB observed in bronchial and colonic epithelial cells, cerebrovascular cells, and hepatic cells. In this report, the authors present ARSB immunostaining in a colonic microarray and show differences in distribution, intensity, and pattern of ARSB staining among normal colon, adenomas, and adenocarcinomas. Distinctive, intense luminal membrane staining was present in the normal epithelial cells but reduced in the malignancies and less in the grade 3 than in the grade 1 adenocarcinomas. In the normal cores, a distinctive pattern of intense cytoplasmic positivity at the luminal surface was followed by reduced staining deeper in the crypts. ARSB enzymatic activity was significantly greater in normal than in malignant tissue. These study findings affirm extra-lysosomal localization of ARSB and suggest that altered ARSB immunostaining and reduced activity may be useful indicators of malignant transformation in human colonic tissue. (J Histochem Cytochem 59:328-335, 2011)

Increased Expression of Colonic Wnt9A through Sp1-mediated Transcriptional Effects involving Arylsulfatase B, Chondroitin 4-Sulfate, and Galectin-3

“…However, the current study findings demonstrate that a transcriptional mechanism leading to increased expression of Wnt9A and attributable to carrageenan-induced decline in ARSB activity, contributes to the carcinogenic potential of carrageenan in human colonic epithelium. Previously, decline in ARSB was demonstrated in malignant colonic tissues and in metastatic colonic epithelial cells (30,31).…”

Differential effects of estrogen exposure on arylsulfatase B, galactose-6-sulfatase, and steroid sulfatase in rat prostate development

“…Antibody specific to native C4S (4D1, Abnova, Littleton, CO) was added to lysates in tubes at a concentration of 1 µg/mg of tissue protein, and tubes were rotated overnight in a shaker at 4°C. Next, 100 µl of pre-washed Protein L-Agarose (SCBT, Santa Cruz, CA) was added to each tube, tubes were incubated overnight at 4°C, and the Protein L-Agarose treated beads were washed three times with PBS containing Protease Inhibitor Cocktail, as previously [2, 4]. The precipitate was eluted with dye-free elution buffer and subjected to sulfated GAG assay.…”

Hypoxia Reduces Arylsulfatase B Activity and Silencing Arylsulfatase B Replicates and Mediates the Effects of Hypoxia

“…Our recent reports have indicated that ARSB activity is reduced in malignant colonic and mammary epithelial cells [1], [3], [22], [23] and in uncorrected cystic fibrosis bronchial epithelial cells [24]. Decline in ARSB activity has lead to reduced IL-8 secretion and increased IL-8 sequestration by bronchial epithelial cells [6] and increased cell-based kininogen and reduced bradykinin secretion by normal rat kidney epithelial cells [4].…”

“…In addition to lysosomal localization, ARSB is also present in the cell membrane of epithelial and endothelial cells [1]–[6]. The sulfatase enzymes are a family of enzymes that each have highly specified chemical function, and ARSB removes the 4-sulfate group from N-acetylgalactosamine-4-sulfate at the non-reducing end of C4S and DS, and thereby can regulate the degradation of these sulfated glycosaminoglycans (GAGs) [7]–[9].…”