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Decline in Arylsulfatase B and Increase in Chondroitin 4-Sulfotransferase Combine to Increase Chondroitin 4-Sulfate in Traumatic Brain Injury

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posted on 28.01.2016, 00:00 by S. Bhattacharyya, X. Zhang, L. Feferman, D. Johnson, FC Tortella, M. Guizzetti, JK Tobacman
In an established rat model of penetrating ballistic-like brain injury (PBBI), arylsulfatase B (ARSB; N-acetylgalactosamine 4-sulfatase) activity was significantly reduced at the ipsilateral site of injury, but unaffected at the contralateral site or in sham controls. In addition, the ARSB substrate chondroitin 4-sulfate (C4S) and total sulfated glycosaminoglycans increased. The mRNA expression of chondroitin 4-sulfotransferase 1 (C4ST1; CHST11) and the sulfotransferase activity rose at the ipsilateral site of injury (PBBI-I), indicating contributions from both increased production and reduced degradation to the accumulation of C4S. In cultured, fetal rat astrocytes, following scratch injury, the ARSB activity declined and the nuclear hypoxia inducible factor (HIF)-1α increased significantly. In contrast, sulfotransferase activity and chondroitin 4-sulfotransferase expression increased following astrocyte exposure to TGF-β1, but not following scratch. These different pathways by which C4S increased in the cell preparations were both evident in the response to injury in the PBBI-I model. Hence, findings support effects of injury due to mechanical disruption inhibiting ARSB and to chemical mediation by TGF-β1 increasing CHST11 expression and sulfotransferase activity. The increase in C4S following TBI is due to contributions from impaired degradation and enhanced synthesis of C4S which combine in the pathogenesis of the glial scar.

Funding

This work was supported by the NIH CTSA ULI RR029879 (to JKT), by NIH/NIAAA AA021876 (to MG), and by VHA I01BX001819 (to MG).

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Publisher Statement

This is the pre-peer reviewed version of the following article: Bhattacharyya, S., Zhang, X. L., Feferman, L., Johnson, D., Tortella, F. C., Guizzetti, M. and Tobacman, J. K. Decline in arylsulfatase B and Increase in chondroitin 4-sulfotransferase combine to increase chondroitin 4-sulfate in traumatic brain injury. Journal of Neurochemistry. 2015. 134(4): 728-739. DOI: 10.1111/jnc.13156, which has been published in final form at http://onlinelibrary.wiley.com/doi/10.1111/jnc.13156/abstract.

Publisher

Wiley Periodicals Inc.

issn

0022-3042

Issue date

01/01/2015

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