Spatiotemporal expression of chondroitin 6-sulfotransferase (C6ST) in regeneration of crush-injured sciatic nerves of adult rats

Abstract

We observed 6-fold increase in water-soluble 6-sulfated chondroitin isoforms in post-crush sciatic nerves and hypothesized that this was due to upregulated expression of chondroitin 6-sulfotransferase (C6ST) in response to crush injury. To address this in adult rats, we cloned a cDNA of rat C6ST (rC6ST), based on published sequences of the mouse and human homologue. Sequence analysis of the newly cloned cDNA revealed an open reading frame of 1425 nucleotides encoding a protein of 474 amino acids, bearing high homology to the mouse, human and chick counterparts. Transient transfections of rC6ST in COS-7 cells produced enzyme activity that catalyzed transfer of sulfate to C-6 of GalNAc of polymer chondroitin. In the crush-injured sciatic nerve, the increase in rC6ST transcript was found to peak by 14-d post-crush, in phase with that of the sulfated chondroitin isoforms in a parallel study. In situ hybridization located elevated rC6ST transcripts in GFAP-positive Schwann cells and ED-1 positive macrophages. The results suggest that the upregulated expression of C6ST contributes to chondroitin isoform products that fine-tune the microenvironment for axonal regrowth in the crushed sciatic nerve. (SPON: The Hong Kong Society of Neuroscience). Supported by HKU7249/01M