Glucosyldiacylglycerol enhances reciprocal activation of prourokinase and plasminogen.
Reciprocal activation of prourokinase (pro-u-PA) and plasminogen is an important mechanism in the initiation and propagation of local fibrinolytic activity. We found that glucosyldiacylglycerol (GDG) enhanced the reciprocal activation by 1.5- to 2-fold at 0.7-16 microM, accompanying increased conversions of both zymogens to active two-chain forms. The reciprocal activation system consists of (i) plasminogen activation by pro-u-PA to form plasmin, (ii) pro-u-PA activation by the resulting plasmin to form two-chain u-PA (tcu-PA), and (iii) plasminogen activation by the resulting tcu-PA. Whereas GDG minimally affected steps (ii) and (iii) in isolated systems, it markedly enhanced step (i) in the absence of the conversion of pro-u-PA to tcu-PA. GDG significantly increased the intrinsic fluorescence of pro-u-PA (6.7%), but not that of tcu-PA or plasminogen. The large change in intrinsic fluorescence suggests that GDG selectively affects pro-u-PA to alter its conformation, and this mechanism may account for enhancement of its intrinsic plasminogen activator activity.
Department of Applied Biological Science, Tokyo Noko University, Fuchu, Tokyo 183-8509, Japan.
Wenhui
W
Wu
Ritsuko
R
Narasaki
Fumihiko
F
Maeda
Keiji
K
Hasumi
D002850:Chromatography, Gel; D004789:Enzyme Activation; D004792:Enzyme Precursors / Q000378:metabolism*; D005340:Fibrinogen / Q000378:metabolism; D005470:Fluorometry; D006017:Glycolipids / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D006801:Humans; D010958:Plasminogen / Q000378:metabolism; D010960:Plasminogen Activators / Q000378:metabolism; D011994:Recombinant Proteins / Q000378:metabolism*; D044647:Sargassum / Q000201:enzymology*; D014568:Urokinase-Type Plasminogen Activator / Q000378:metabolism*
D004792:Enzyme Precursors; D006017:Glycolipids; D011994:Recombinant Proteins; C014571:glucosyl diacylglycerol; D005340:Fibrinogen; D010958:Plasminogen; D010960:Plasminogen Activators; D014568:Urokinase-Type Plasminogen Activator; C067551:saruplase