Hypoxia Reduces Arylsulfatase B Activity in Human Bronchial and Colonic Epithelial Cells and Arylsulfatase B Expression Modifies HIF‐1alpha

The enzyme arylsulfatase B (ARSB; N‐acetylgalactosamine‐4‐sulfatase), which removes 4‐sulfate groups from the non‐reducing end of chondroitin‐4‐sulfate, is present at the cell membrane, as well as in lysosomes. Sulfatase activity requires modification of a critical cysteine residue at the active site. When primary human bronchial or colonic epithelial cells were exposed to a 5% oxygen environment, ARSB activity declined to ~59% and ~70% of the baseline value in one hour, without changes in steroid sulfatase, galactose‐6‐sulfatase, or arylsulfatase A activity. HIF‐1alpha increased by ~50% and ~33% from baseline values. ARSB silencing in a normal oxygen environment was associated with increases in HIF‐1alpha of ~61% and ~81%, and ARSB overexpression led to declines in HIF‐1alpha of ~37% and ~54%, respectively. Hypoxia resulted in significant increases in the sulfated glycosaminoglycan content in the bronchial and colonic epithelial cells. Also, cellular protein‐SH content was reduced by either ARSB silencing or by hypoxia. All results were statistically significant (p<0.01 or p<0.001, unpaired t‐test). The combination of ARSB silencing and hypoxia produced no further increase in HIF‐1alpha. These study findings indicate that some of the intracellular effects of oxygen may occur through an ARSB‐mediated pathway that regulates sulfate metabolism and associated oxidation‐reduction reactions.