Disease relevance of CHST1

• The incidence of GST1 0 in 41 liver biopsy samples from patients suffering from various liver diseases was investigated using polyacrylamide gel isoelectric focusing [1].
• Dot blot analysis has shown that human C4ST is strongly expressed in colorectal adenocarcinoma and peripheral blood leukocytes, whereas strong expression of human chondroitin 6-sulfotransferase (C6ST) is observed in aorta and testis [2].
• We studied genetic polymorphisms in the glutathione-S-transferase-1 (GST-1) gene region and the interleukin-1beta (IL-1beta) promoter region in patients with Parkinson's disease (PD, n = 361), as well as controls (n = 257) [3].
• Macular corneal dystrophy (MCD) is an autosomal recessive disease characterized by corneal opacities and caused by mutations in a carbohydrate sulfotransferase gene, known as CHST6 [4].
• It was expressed in Escherichia coli as a fusion with human glutathione S-transferase (hGST) and was confirmed by Western blotting analysis [5].

High impact information on CHST1

• Recently, three related sulfotransferases (keratan sulfate galactose-6-sulfotransferase [KSGal6ST], high endothelial cell N-acetylglucosamine-6-sulfotransferase [GlcNAc6ST], and human GlcNAc6ST) were cloned, which can generate Gal-6-sulfate and GlcNAc-6-sulfate in GlyCAM-1 [6].
• The increased production of ethylene during carnation petal senescence regulates the transcription of the GST1 gene encoding a subunit of glutathione-S-transferase [7].
• An ethylene-responsive enhancer element is involved in the senescence-related expression of the carnation glutathione-S-transferase (GST1) gene [7].
• Deletion analysis of the 5' flanking sequences of GST1 identified a single positive regulatory element of 197 bp between -667 and -470 necessary for ethylene-responsive expression [7].
• Disruption of the N-capping motif of helix 9 in hGST A1-1 alters the conformational dynamics of the C-terminal region and, consequently, the features of the H-site to which hydrophobic substrates (e.g. 1-chloro-2,4-dinitrobenzene (CDNB)) and nonsubstrates (e.g. 8-anilino-1-naphthalene sulfonate (ANS)) bind [8].

Chemical compound and disease context of CHST1

• The human glutathione S-transferases: a case-control study of the incidence of the GST1 0 phenotype in patients with adenocarcinoma [9].

Biological context of CHST1

• Increased CHST1 or CHST2 expression by a cell line expressing low-level L-selectin ligand activity during in vitro flow chamber assays increased rolling leukocyte numbers, reduced rolling velocities, and enhanced leukocyte rolling under higher shear stresses [10].
• In the present study, we screened DNA from 48 healthy Japanese volunteers for SNPs at the CHST1 and CHST3 gene loci, by means of direct sequencing combined with a polymerase chain reaction method for amplifying genomic DNA, and characterized 77 SNPs and four insertion-deletion polymorphisms [11].
• Therefore, human vascular endothelium cDNA libraries were screened to identify sulfotransferases homologous to chicken chondroitin 6-sulfotransferase (C6ST) [12].
• KSGal6ST was assigned to chromosome 11p11 [13].
• On the basis of the acceptor substrate specificity, we propose keratan sulfate Gal-6-sulfotransferase (KSGal6ST) for the name of the newly cloned sulfotransferase [13].

Anatomical context of CHST1

• These results suggest that CHST1 and CHST2 contribute to the generation of optimal L-selectin ligands in vascular endothelial cells at sites of inflammation [10].
• CHST1 and CHST2 sulfotransferase expression by vascular endothelial cells regulates shear-resistant leukocyte rolling via L-selectin [10].
• A human umbilical vein endothelial cell line, EA.hy926, displayed functional L-selectin ligands that correlated with CHST1 and CHST2 expression in the absence of CHST4 expression [10].
• When poly(A)+ RNAs from the chick embryo cornea and brain were probed with the human KSGal6ST cDNA in Northern hybridization, a clear band with about 2.8 kilobases was detected [13].
• When the cDNA was introduced into a eukaryotic expression vector and transfected in COS-7 cells, keratan sulfate sulfotransferase activity was overexpressed, but C6ST activity was not increased over that of the control [13].

Associations of CHST1 with chemical compounds

• These observations suggest that KSGal6ST may participate in the biosynthesis of keratan sulfate in the brain and cornea [13].
• Sulfation of sialyl N-acetyllactosamine oligosaccharides and fetuin oligosaccharides by keratan sulfate Gal-6-sulfotransferase [14].
• We have previously cloned keratan sulfate Gal-6-sulfotransferase (KSGal6ST), which transfers sulfate from 3'-phosphoadenosine 5'-phosphosulfate to position 6 of Gal residue of keratan sulfate [14].
• Analysis of the degradation products with paper chromatography and high performance liquid chromatography provided evidence that C6ST transferred sulfate to position 6 of galactose residue which was glycosidically linked to N-acetylglucosamine 6-sulfate residue or to N-acetylglucosamine residue [15].
• Carbohydrate sulfation was implicated in this process, when it was demonstrated that carbohydrate sulfotransferase-mediated sulfation of N-acetylglucosamine (GlcNAc) within sialyl Lewis X of cognate endothelial ligands for L-selectin was an essential modification for L-selectin binding [16].

Other interactions of CHST1

• Activities and expression pattern of the carbohydrate sulfotransferase GlcNAc6ST-3 (I-GlcNAc6ST): functional implications [17].
• PURPOSE: Mutations in a new carbohydrate sulfotransferase gene (CHST6) encoding corneal N-acetylglucosamine-6-sulfotransferase (C-GlcNac-6-ST) have been identified as the cause of macular corneal dystrophy (MCD) in various ethnicities [18].
• Mutation analysis of the carbohydrate sulfotransferase gene in Vietnamese with macular corneal dystrophy [18].

Analytical, diagnostic and therapeutic context of CHST1

• Molecular cloning and characterization of human keratan sulfate Gal-6-sulfotransferase [13].
• The human C6ST gene structure has been elucidated and exhibits an intron-less coding region, and the gene has been mapped to human chromosome 11 by radiation hybrid panel mapping [19].
• Northern blot analysis using poly (A)+ RNA from 12-d-old chick embryos indicated that the message of C6ST was expressed not only in the cartilage but also in the cornea in which keratan sulfate is actively synthesized [15].
• Partial purification of midgut GSTs by size-exclusion and glutathione affinity chromatography resulted in a series of isoelectric focusing bands, with the major one corresponding to the predicted isoelectric point of the M. sexta GST1 [20].
• The immunofluorescence in human lung sections was observed with the antibodies which were raised against GST psi and GST alpha-epsilon of human liver and GST pi of human placenta indicating that the isoenzymes corresponding to three gene loci, GST1, GST2, and GST3 are present in human lung [21].

References