Importance of GlcUAbeta1-3GalNAc(4S,6S) in chondroitin sulfate E for t-PA- and u-PA-mediated Glu-plasminogen activation.
Chondroitin sulfate E (CSE) markedly enhanced plasminogen activation by tissue plasminogen activators (t-PAs) and urinary plasminogen activator (u-PA) in vitro; in the presence of 10 microg/ml of CSE, the potentiation factors of single chain of t-PA, two chain of t-PA and u-PA were 400, 140 and 130, respectively. Though the potentiation activity of CSE gradually decreased when it was depolymerized by chondroitinase ABC, the specific disaccharide from CSE still showed significant activity. Glycosaminoglycan (GAG) from sea cucumber, which possesses a very similar core structure to CSE, but has additional sulfated fucose branches exhibit very weak activity. These results suggested that the minimal structural requirement in CSE to enhance plasminogen activation by plasminogen activators is GlcUAbeta1-3GalNAc(4S,6S) and that additional branching sugars abolish the activity.
Sakai
T
T
Seikagaku Corporation, Central Research Laboratories, 1253, Tateno-3 chome, Tokyo 207-0021, Higashiyamato, Japan.
Kyogashima
M
M
Kariya
Y
Y
Urano
T
T
Takada
Y
Y
Takada
A
A
D000818:Animals; D002236:Carbohydrate Conformation; D002240:Carbohydrate Sequence; D019765:Chondroitin ABC Lyase / Q000378:metabolism; D002809:Chondroitin Sulfates / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*; D004187:Disaccharides / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation / Q000187:drug effects; D006025:Glycosaminoglycans / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D010958:Plasminogen / Q000187:drug effects / Q000378:metabolism*; D010960:Plasminogen Activators / Q000187:drug effects* / Q000494:pharmacology; D012616:Sea Cucumbers / Q000737:chemistry; D013329:Structure-Activity Relationship; D013463:Sulfuric Acid Esters / Q000737:chemistry / Q000494:pharmacology*; D010959:Tissue Plasminogen Activator / Q000187:drug effects / Q000494:pharmacology; D014568:Urokinase-Type Plasminogen Activator / Q000187:drug effects / Q000494:pharmacology
D004187:Disaccharides; D006025:Glycosaminoglycans; D013463:Sulfuric Acid Esters; C038142:chondroitin sulfate glycosaminoglycan; C423351:glucuronic acid-1-3-N-acetyl-4,6-disulfoxygalactosamine; D010958:Plasminogen; D002809:Chondroitin Sulfates; D010960:Plasminogen Activators; D010959:Tissue Plasminogen Activator; D014568:Urokinase-Type Plasminogen Activator; D019765:Chondroitin ABC Lyase