Disease relevance of Gal3st1

• To investigate the cellular functions of sulfated glycosphingolipids, we introduced the cerebroside sulfotransferase (CST) gene into J5 cells, a subclone of 3LL Lewis lung carcinoma cells [1].
• Cerebroside sulfotransferase deficiency ameliorates L-selectin-dependent monocyte infiltration in the kidney after ureteral obstruction [2].
• Disruption of the Cst gene in mice results in male infertility due to the arrest of spermatogenesis prior to the metaphase of the first meiosis [3].
• METHODS: The threshold for the clonic seizures (CST) induced by acute intravenous administration of gamma-aminobutyric acid (GABA)-antagonist pentylenetetrazole (PTZ) was assessed in male and female mice [4].

High impact information on Gal3st1

• To investigate the physiological role of sulfoglycolipids and to determine whether sulfatide and seminolipid are biosynthesized in vivo by a single sulfotransferase, Cst-null mice were generated by gene targeting [5].
• Although compact myelin was preserved, Cst(-/-) mice displayed abnormalities in paranodal junctions [5].
• Cst(-/-) mice lacked sulfatide in brain and seminolipid in testis, proving that a single gene copy is responsible for their biosynthesis [5].
• On the other hand, Cst(-/-) males were sterile because of a block in spermatogenesis before the first meiotic division, whereas females were able to breed [5].
• Cst(-/-) mice were born healthy, but began to display hindlimb weakness by 6 weeks of age and subsequently showed a pronounced tremor and progressive ataxia [5].

Chemical compound and disease context of Gal3st1

• To investigate the significance of sialylation and sulfation of lactosylceramide in transformed cells, we established ganglioside GM3- and lactosylsulfatide (SM3)-reconstituted cells by transfecting cDNAs of GM3 synthase and cerebroside sulfotransferase into the J5 subclone of 3LL Lewis lung carcinoma cells [6].
• Moreover, CST-deficiency ameliorates L-selectin-dependent monocyte infiltration in the kidney after ureteral obstruction, an experimental model of renal interstitial inflammation, indicating that sulfatide is an endogenous ligand of L-selectin [7].

Biological context of Gal3st1

• These observations suggest that the tissue-specific expression of the CST gene is explained by alternative usage of multiple 5'-UTR exons flanked with tissue-specific promoters [8].
• In addition, we isolated CST genomic DNA clones from a mouse genomic library [8].
• Although the rates of cell proliferation in vitro for mock and CST transfectants were similar, tumorigenicity of J5/CST-1 and -2 cells inoculated into syngeneic C57/BL6 mice was greatly decreased or even absent [1].
• RESULTS: At baseline, diestrus females had a higher CST compared with males and estrus females [4].
• Ovariectomy brought the baseline CST to the male level and resulted in significant expression of both phases of morphine effect but did not abolish the sex difference in responsiveness to morphine [4].

Anatomical context of Gal3st1

• In the present study, we examined oligodendrocytes differentiation in cerebroside sulfotransferase-null mice (Cst(-/-)) that lack sulfatide but express GalC [9].
• To examine differences in transcripts in various tissues, we isolated CST cDNA clones from stomach, small intestine, brain, kidney, and testis by 5'-RACE analysis [8].
• Compared with wild-type mice, Cst(-/-) mice showed a considerable reduction in the number of monocytes/macrophages that infiltrated the interstitium after UUO [2].
• Biochemical analyses showed Schwann cells to be enriched in the activities of enzymes characteristic of the myelin-forming cells: 2'3'-cyclic nucleotide 3'-phosphodiesterase (CNP), cerebroside sulfotransferase (CST) and UDP-galactose: ceramide galactosyltransferase (CGalT) [10].
• Our findings show that the defect is in the germ cell side, as evidenced by a transplantation analysis, in which wild-type spermatogonia expressing the green fluorescent protein were injected into the seminiferous tubules of CST-null testis [3].

Associations of Gal3st1 with chemical compounds

• We established the stable CST transfectants, J5/CST-1 and J5/CST-2 clones, highly expressing sulfated lactosylceramide (SM3) [1].
• These results demonstrate that endogenous SM3 negatively regulates beta(1) integrin expression at the transcriptional level, and the decrease of alpha integrin proteins in the CST transfectants was due to the post-transcriptional modification [1].
• Deglycosylation by endoglycosidase H treatment clearly demonstrated that the precursor form of beta(1) integrin, possessing high mannose oligosaccharide chains, was preferentially decreased in the CST transfectants [1].
• Galactosylceramide sulfotransferase (EC 2.8.2.11) catalyzes the biosynthesis of sulfatide from galactocerebroside and adenosine 3'-phosphate 5'-phosphosulfate (PAPS) [11].
• Cerebroside-sulfotransferase (CST), creatine-phosphokinase (CPK), and 3-hydroxy-3-methylglutaroyl CoA (HMG CoA) reductase activity, protein, and DNA content were measured in an easy-to-perform organotypic culture system of newborn normal and jimpy brains [12].

Other interactions of Gal3st1

• The activities of ceramide galactosyl transferase and cerebroside sulfotransferase and levels of myelin basic protein were similarly depressed [13].
• The developmental activity pattern of cerebroside-sulfotransferase, cyclic nucleotide phosphohydrolase, and beta-hydroxy-beta-methyl glutaryl-coenzyme A-reductase and the synthesis and deposition of sulfatide and cholesterol in culture were estimated [14].
• In contrast, cerebroside sulfotransferase activities were increased by 257 and 172% in young and adult Trembler sciatic nerves, respectively [15].
• Age-related changes in cerebroside sulfotransferase (measured in brain) and arylsulfatase A and cerebroside B-galactosidase (measured in brain and liver) were the same for shiverer and control mice [16].

Analytical, diagnostic and therapeutic context of Gal3st1

• Northern-blot analysis and subquantitative reverse transcription-PCR (RT-PCR) analysis showed that the CST gene is preferentially transcribed in stomach, small intestine, brain, kidney, lung, and testis, in that order [8].
• The defective sulfatide synthesis which has been shown in vivo in jimpy brains could also be demonstrated in organ cultures of jimpy mice in the form of lowered CST activity in the homogenate as well as reduced 35SO4 incorporation into 35SO4-sulfatide [12].
• Theophylline reduces the activity of cerebroside-sulfotransferase, a key enzyme in myelination, in cell cultures from newborn mouse brain [17].
• Dispersive analysis of turnover rates of a CST reactor by flow-through microfluorometry under conditions of growth [18].

References