Effects of carbocisteine on altered activities of glycosidase and glycosyltransferase and expression of Muc5ac in SO2-exposed rats.
Carbocisteine is a mucoregulatory drug regulating fucose and sialic acid contents in mucus glycoprotein. To investigate the mechanism of carbocisteine action, we evaluated the effects of carbocisteine on the activity of fucosidase, sialidase, fucosyltransferase and sialyltransferase, and on the expression of Muc5ac mRNA in the airway epithelium of SO(2)-exposed rats. Wistar rats were repeatedly exposed to a 300-ppm SO(2) gas for 44 days. Carbocisteine (125 and 250 mg/kg x2/day) was administered for 25 days after 20 days of SO(2) gas exposure. These enzyme activities were measured by fluorogenic substrate or glycoproteinic exogenous acceptor method. The expression levels of Muc5ac mRNA and protein were determined with real-time reverse transcriptase-polymerase chain reaction (real-time RT-PCR) and enzyme-linked immunosorbent assay (ELISA), respectively. Carbocisteine (250 mg/kg x2/day) inhibited all the changes in these enzyme activities and the expressions of Muc5ac mRNA and protein in the lung after repeated SO(2) exposure. These findings suggest that carbocisteine may normalize fucose and sialic acid contents in mucin glycoprotein through regulation of these enzyme activities, and inhibition of both Muc5ac mRNA and protein expressions in SO(2)-exposed rats.
Ishibashi
Yuji
Y
Research Center, Kyorin Pharmaceutical Co., Ltd., 329-0114 Tochigi, Japan. ISHIBASHI.Yuji@nims.go.jp
Kobayashi
Fumiyoshi
F
Idesawa
Akira
A
Taniguchi
Akiyoshi
A
Matsuzawa
Shigeki
S
D000818:Animals; D003545:Cysteine / Q000031:analogs & derivatives* / Q000502:physiology*; D006026:Glycoside Hydrolases / Q000378:metabolism*; D016695:Glycosyltransferases / Q000378:metabolism; D008297:Male; D055271:Mucin 5AC; D009077:Mucins / Q000096:biosynthesis*; D009439:Neuraminidase / Q000378:metabolism; D012313:RNA / Q000096:biosynthesis; D051381:Rats; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013431:Sulfates / Q000494:pharmacology*; D005644:alpha-L-Fucosidase / Q000378:metabolism
C524680:Muc5ac protein, rat; D055271:Mucin 5AC; D009077:Mucins; D013431:Sulfates; D012313:RNA; D016695:Glycosyltransferases; D006026:Glycoside Hydrolases; D009439:Neuraminidase; D005644:alpha-L-Fucosidase; D003545:Cysteine