Inhibition of hyaluronan export from human fibroblasts by inhibitors of multidrug resistance transporters
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Inhibition of hyaluronan export from human fibroblasts by inhibitors of multidrug resistance transporters. / Prehm, Peter; Schumacher, Udo.
In: BIOCHEM PHARMACOL, Vol. 68, No. 7, 01.10.2004, p. 1401-10.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Inhibition of hyaluronan export from human fibroblasts by inhibitors of multidrug resistance transporters
AU - Prehm, Peter
AU - Schumacher, Udo
PY - 2004/10/1
Y1 - 2004/10/1
N2 - In a previous report we described the export of hyaluronan from Streptococcus pyogenes by an ABC transporter. Extending these findings a sequence homology search against human proteins revealed a strong homology to the multidrug resistance transporter ABC-B (MDR-1) and ABC-C (MRP 5). Using several inhibitors directed against these and other transporters, a decreased hyaluronan production in cell culture as well as in hyaluronan synthase activity in purified membrane fractions was observed. The inhibitory capacity (IC(50) concentrations) was compared the with reported IC(50)- or the K(i)-concentrations for individual transporters. These analyses revealed that hyaluronan is synthesized within the cytoplasm of mammalian cells and actively secreted into the pericellular space by energy dependent transport proteins. While inhibition of several transport proteins resulted in a decrease of hyaluronan export, inhibition of the MRP5 transporter was the most effective one to decrease hyaluronan in the cell culture supernatant indicating that hyaluronan export is one physiological role of this transport protein.
AB - In a previous report we described the export of hyaluronan from Streptococcus pyogenes by an ABC transporter. Extending these findings a sequence homology search against human proteins revealed a strong homology to the multidrug resistance transporter ABC-B (MDR-1) and ABC-C (MRP 5). Using several inhibitors directed against these and other transporters, a decreased hyaluronan production in cell culture as well as in hyaluronan synthase activity in purified membrane fractions was observed. The inhibitory capacity (IC(50) concentrations) was compared the with reported IC(50)- or the K(i)-concentrations for individual transporters. These analyses revealed that hyaluronan is synthesized within the cytoplasm of mammalian cells and actively secreted into the pericellular space by energy dependent transport proteins. While inhibition of several transport proteins resulted in a decrease of hyaluronan export, inhibition of the MRP5 transporter was the most effective one to decrease hyaluronan in the cell culture supernatant indicating that hyaluronan export is one physiological role of this transport protein.
KW - ATP-Binding Cassette Transporters
KW - Biological Transport
KW - Cell Division
KW - Cells, Cultured
KW - Cyclosporins
KW - Drug Resistance, Multiple
KW - Fibroblasts
KW - Humans
KW - Hyaluronic Acid
KW - Multidrug Resistance-Associated Proteins
KW - Synovial Membrane
U2 - 10.1016/j.bcp.2004.06.017
DO - 10.1016/j.bcp.2004.06.017
M3 - SCORING: Journal article
C2 - 15345330
VL - 68
SP - 1401
EP - 1410
JO - BIOCHEM PHARMACOL
JF - BIOCHEM PHARMACOL
SN - 0006-2952
IS - 7
ER -