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Defining the Role of Arylsulfatase B (N‐Acetylgalactosamine 4‐Sulfatase) in Cellular Metabolism
Author(s) -
Bhattacharyya Sumit,
Feferman Leo,
Tobacman Joanne
Publication year - 2015
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.29.1_supplement.725.16
Subject(s) - biochemistry , chemistry , biology , microbiology and biotechnology
Arylsulfatase B (ARSB; N‐acetylgalactosamine 4‐sulfatase) is the lysosomal and membrane enzyme that removes 4‐sulfate groups from the non‐reducing end of chondroitin 4‐sulfate and dermatan sulfate, and thereby regulates their degradation. Studies have demonstrated decline in ARSB in patients with cystic fibrosis and in malignant human mammary, prostate, and colonic epithelial tissues. Several molecules, including Interleukin‐8, high molecular weight kininogen, BMP4, and galectin‐3, bind preferentially to more or less sulfated C4S, affecting cell‐cell and cell‐extracellular matrix interactions. Previously, we reported that hypoxia reduced ARSB activity and that decline in ARSB replicated the effects of hypoxia on the expression of 84 genes in a hypoxia gene array. Both hypoxia and silencing ARSB decreased the ratios of reduced glutathione to GSSG and of cellular sulfhydryls to sulfides. Recent experiments in ARSB‐deficient mice and human epithelial cells following ARSB silencing have shown: increased serum lactate, increased 2,3‐DPG, increased extracellular acidfication, reduced oxygen consumption rate, reduced mitochondrial membrane potential, disruption of inner and outer mitochondrial membranes by electron microscopy, and increased NADPH to NADP and NADH to NAD ratios. These findings suggest profound effects of decline in ARSB on cellular metabolism and oxidation‐reduction reactions. Sulfate reduction is utilized in protists, plants, and algae for energy production. Impairment of sulfate reduction due to unavailability of sulfate due to ARSB deficiency may help to explain the occurrence of aerobic glycolysis in human cells.