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

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Title: Hypoxia Reduces Arylsulfatase B Activity and Silencing Arylsulfatase B Replicates and Mediates the Effects of Hypoxia
Author(s): Bhattacharyya, Sumit; Tobacman, Joanne K.
Subject(s): Hypoxia Arylsulfatase B
Abstract: This report presents evidence of 1) a role for arylsulfatase B (ARSB; N-acetylgalactosamine-4-sulfatase) in mediating intracellular oxygen signaling; 2) replication between the effects of ARSB silencing and hypoxia on sulfated glycosaminoglycan content, cellular redox status, and expression of hypoxia-associated genes; and 3) a mechanism whereby changes in chondroitin-4-sulfation that follow either hypoxia or ARSB silencing can induce transcriptional changes through galectin-3. ARSB removes 4-sulfate groups from the non-reducing end of chondroitin-4-sulfate and dermatan sulfate and is required for their degradation. For activity, ARSB requires modification of a critical cysteine residue by the formylglycine generating enzyme and by molecular oxygen. When primary human bronchial and human colonic epithelial cells were exposed to 10% O261 h, ARSB activity declined by ,41% and ,30% from baseline, as nuclear hypoxia inducible factor (HIF)-1a increased by ,53% and ,37%. When ARSB was silenced, nuclear HIF-1a increased by ,81% and ,61% from baseline, and mRNA expression increased to 3.73 (60.34) times baseline. Inversely, ARSB overexpression reduced nuclear HIF-1a by ,37% and ,54% from baseline in the epithelial cells. Hypoxia, like ARSB silencing, significantly increased the total cellular sulfated glycosaminoglycans and chondroitin-4-sulfate (C4S) content. Both hypoxia and ARSB silencing had similar effects on the cellular redox status and on mRNA expression of hypoxia-associated genes. Transcriptional effects of both ARSB silencing and hypoxia may be mediated by reduction in galectin-3 binding to more highly sulfated C4S, since the galectin-3 that co-immunoprecipitated with C4S declined and the nuclear galectin-3 increased following ARSB knockdown and hypoxia.
Issue Date: 2012
Publisher: Public Library of Science
Citation Info: Bhattacharyya, S. & Tobacman, J. K. 2012. Hypoxia reduces arylsulfatase B activity and silencing arylsulfatase B replicates and mediates the effects of hypoxia. PLoS One, 7(3): e33250. doi:10.1371/journal.pone.0033250
Type: Article
Description: This is a copy of an article published in PLoS ONE by the Public Library of Science. This is an open-access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication. doi:10.1371/journal.pone.0033250
URI: http://hdl.handle.net/10027/8780
ISSN: 1932-6203
Sponsor: The sources of funding were VA Merit Review and Clinical and Translational Science Award (CTSA) UL1 RR029879. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Date Available in INDIGO: 2012-11-15
2012-11-15
 

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