Title
Inhibition of urokinase-type and tissue-type plasminogen activator - Mediated plasminogen activation by doxycycline
Author
Hanemaaijer, R.
Visser, H.
van den Hoogen, C.M.
Sorsa, T.
van Hinsbergh, V.W.M.
Gaubius Laboratory Dept. of Periodontology, Univ. of Helsinki, Helsinki, Finland TNO Preventie en Gezondheid
Publication year
1996
Abstract
Degradation and remodelling of the extracellular matrix is an essential feature in many pathophysiological processes, especially in invasive and angiogenesis-related diseases. At least two families of proteolytic enzymes have been suggested to play a role in this process: matrix metalloproteinases (MMPs) and plasminogen activators, in particular urokinase-type plasminogen activator (u-PA). Doxycycline, a tetracycline derivative, has been shown to be able to inhibit MMP catalytic activities, a function independent of its antimicrobial properties. In this study we show that doxycycline also inhibits the activation of plasminogen by urokinase (u-PA) or tissue-type plasminogen activator (t-PA) at concentrations of 25-50 μM. It did not affect the activity of plasmin itself or the amidolytic activity of u-PA. This observation extends the insight in the inhibitory effect of doxycycline on cellular proteolysis and may support the rationale for the use of doxycycline in the treatment of destructive diseases like rheumatoid arthritis.
Subject
Biology
doxycycline
tissue plasminogen activator
urokinase
conference paper
fibrinolysis
human
plasminogen activation
priority journal
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http://resolver.tudelft.nl/uuid:a152c2c8-57c3-439a-8e9d-4acafabd7f33
TNO identifier
233527
ISSN
0268-9499
Source
Fibrinolysis, 10 (SUPPL. 2), 109-111
Document type
article