2002
DOI: 10.1046/j.1432-1033.2002.03217.x
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Inhibition of hyaluronan synthesis in Streptococcus equi FM100 by 4‐methylumbelliferone

Abstract: As observed previously in cultured human skin fibroblasts, a decrease of hyaluronan production was also observed in group C Streptococcus equi FM100 cells treated with 4-methylumbelliferone (MU), although there was no effect on their growth. In this study, the inhibition mechanism of hyaluronan synthesis by MU was examined using Streptococcus equi FM100, as a model. When MU was added to a reaction mixture containing the two sugar nucleotide donors and a membrane-rich fraction as an enzyme source in a cellfree … Show more

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Cited by 43 publications
(32 citation statements)
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“…The results were somewhat unexpected because phospholipid composition has been reported to be important for HAS activity in bacterial cells (28,(37)(38)(39)(40), where cardiolipin (not present in the mammalian plasma membrane (41)) is the best activator of hyaluronan synthesis and restores HAS activity also after 4-methylumbelliferone treatment (28). However, by disrupting microvilli (43) M␤CD could reduce the plasma membrane surface area available for HAS, and therefore indirectly inhibit hyaluronan synthesis in those cells expressing particularly high levels of HAS.…”
Section: Discussionmentioning
confidence: 90%
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“…The results were somewhat unexpected because phospholipid composition has been reported to be important for HAS activity in bacterial cells (28,(37)(38)(39)(40), where cardiolipin (not present in the mammalian plasma membrane (41)) is the best activator of hyaluronan synthesis and restores HAS activity also after 4-methylumbelliferone treatment (28). However, by disrupting microvilli (43) M␤CD could reduce the plasma membrane surface area available for HAS, and therefore indirectly inhibit hyaluronan synthesis in those cells expressing particularly high levels of HAS.…”
Section: Discussionmentioning
confidence: 90%
“…The microenvironment of HAS, especially the phospholipid composition of the plasma membrane, is important for HAS activity (28,(37)(38)(39)(40). Cardiolipin is the best activator of hyaluronan synthesis in Streptococcus equi FM100 and exogenous cardiolipin was reported to restore the activity of HAS sup- …”
mentioning
confidence: 99%
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“…For example, MU was found to inhibit HA synthesis in cultured human skin fibroblasts but to have no effect on the synthesis of any other glycosaminoglycan (39). MU did not affect expression of the HAS gene but altered the lipid environment of the membrane, especially the distribution of different cardiolipin species, surrounding HAS (40). MU-mediated inhibition of HA synthesis involving the glucuronidation of MU is due, in part, to depletion of the pool of UDP-GlcUA, a common substrate of HAS and UGT.…”
Section: Discussionmentioning
confidence: 95%