Carbocisteine normalizes the viscous property of mucus through regulation of fucosylated and sialylated sugar chain on airway mucins.
Almost all of fucose and sialic acid in mucus are found on the mucus glycoproteins (mucins), and these sugar components on mucins are known to be associated with the viscous property of mucus. We have reported some aspects of carbocisteine, a mucoregulatory drug, correcting fucose and sialic acid contents in mucus. At present, carbocisteine's expectorant action of airway mucus is postulated to involve - the regulation of fucose and sialic acid contents on mucins. However little information is available about the relationship between the viscosity and sugar contents on mucins when treated with carbocisteine. To investigate further the mechanism behind the action of carbocisteine, the present study prepared MUC5AC fusion protein which has tandem repeat regions associated with MUC5AC, and evaluated the effects of carbocisteine on tumor necrosis factor (TNF)-alpha-induced increases of mucus viscosity and sialyl-Lewis x-epitopes antigen, an antigen which consists of fucosylated and sialylated sugar chains on the MUC5AC fusion proteins. Carbocisteine inhibited the TNF-alpha-induced increases of the viscosity and sialyl-Lewis x-epitopes on MUC5AC fusion protein. These findings suggest that carbocisteine may normalize the viscosity of mucus through "balancing" of fucose and sialic acid contents on airway mucins.
Ishibashi
Yuji
Y
Advanced Medical Materials Group, Biomaterials Center, National Institute for Materials Science, Ibaraki, Japan. yuuji.ishibashi@mb.kyorin-pharm.co.jp
Takayama
Goh
G
Inouye
Yoshio
Y
Taniguchi
Akiyoshi
A
D002233:Carbocysteine / Q000494:pharmacology*; D002241:Carbohydrates / Q000737:chemistry / Q000502:physiology*; D045744:Cell Line, Tumor; D000939:Epitopes; D005100:Expectorants / Q000494:pharmacology; D005643:Fucose / Q000378:metabolism; D006801:Humans; D008175:Lung Neoplasms / Q000473:pathology; D009077:Mucins / Q000235:genetics / Q000378:metabolism*; D009093:Mucus / Q000378:metabolism*; D019158:N-Acetylneuraminic Acid / Q000378:metabolism; D009844:Oligosaccharides / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000302:isolation & purification / Q000378:metabolism; D012137:Respiratory System / Q000378:metabolism; D000080506:Sialyl Lewis X Antigen; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism / Q000494:pharmacology; D014783:Viscosity
D002241:Carbohydrates; D000939:Epitopes; D005100:Expectorants; D009077:Mucins; D009844:Oligosaccharides; D011993:Recombinant Fusion Proteins; D000080506:Sialyl Lewis X Antigen; D014409:Tumor Necrosis Factor-alpha; D005643:Fucose; D002233:Carbocysteine; D019158:N-Acetylneuraminic Acid