Fibrinogenolytic and fibrinolytic activity of cell-associated plasmin.

Abstract

Binding of plasmin (ogen) to rat C6 glioma cells is saturable and kringle-domain dependent. This interaction was studied as a model of plasimin(ogen) receptor interactions in nucleated mammalian cells. Apparent l25 I-plasmin dissociation from OS cell binding sites was slow; however, the dissociation rate was increased when the solution contained diisopropyl phosphoryl-plasmin (0.3 juM), fibrinogen (0.16 or 0.8 mg/ml), 1.08 mM D-Val-L-Leu-L-Lys-p-nitroanilide-HCl (S-2251), or e-amino-n-caproic acid (EACA, 5.0 mM). EACA promoted the most rapid dissociation of plasmin. C6 cell-associated plasmin and plasmin in solution demonstrated similar amidase activity. Only specifically bound plasmin (75% of total binding) was active against S-2251. Plasmin that was initially bound to C6 cells digested fibrinogen in a time-and plasmin concentration-dependent manner. o^-Antiplasmin (<* 2 AP, 0.1 fiM) completely inhibited fibrinogenolysis by plasmin that was initially C6 • or human umbilical vein endothelial-cell associated. Since a 2 AP reacts selectively with plasmin in solution (minimally with plasmin bound to cells), fibrinogen digestion by cell-associated plasmin probably occurred only after the plasmin dissociated into solution. Crosslinked fibrin clots were formed in uniform layers over C6 cells. If the cells were incubated with plasmin before addition of fibrinogen and thrombin, the clots were rapidly lysed. <x 2 AP incompletely inhibited fibrinolysis when added after fibrin polymerization (44% inhibition with 0

Retinoids Induce t-PA Synthesis by C6 Glioma Cells -Role in Tumoral Haemorrhagic Necrosis

“…Since local ized fibrinolysis reflects rather the site of concentration of PAs than the systemic fibrinolysis potential, we aimed to characterize the fibrinolyt ic activity of the cRA-treated C6 glioma. Moreover, it has been already suggested that C6 glioma cell-line, which is considered as a model of peri-cellular fibrinolytic activity (3,4,5), produced PAs. Expression and activity of such serine protease has never been thoroughly explored (13), but could explain the localized tumoral fibrinolysis.…”

“…Indeed, it was sug gested that spontaneous tumor brain haemorrhage may be due to a lo cally enhanced fibrinolytic activity which may be aggravated by tumor necrosis and vessel rupture (2). Although plasminogen activators (PAs) produced by C6 cells are not yet characterized, the C6 cell-line is a very characteristic model for fibrinolytic activity of cell-associated plasmin (3,4,5). C6 glioma cells produce in vivo a proteolytic activity related mainly to type IV collagenase (6 ), which is derived from its precursor by activation by plasmin (7).…”

Binding of Anisoylated Lys-Plasminogen Streptokinase Activator Complex to Cells in Culture

“…In the presence of 10 mM EACA, the majority of the APSAC (80-90%) was rapidly recovered in solution. EACA accelerates plasminogen dissociation from cell surfaces in addition to preventirg reassociation (18). EACA probably affects cell-associated APSAC similarly.…”

Dendrobium officinale flos increases neurotrophic factor expression in the hippocampus of chronic unpredictable mild stress‐exposed mice and in astrocyte primary culture and potentiates NGF‐induced neuronal differentiation in PC12 cells

“…For determination of the related signalling pathways, PKI (protein kinase A inhibitor, 10 nM) and U0126 (ERK inhibitor, 2 μM) were used to treat astrocytes for 3 hrs before exposure to DOF extracts, forskolin (10 μM), and TPA (100 nM) (Cao et al, 2018). To evaluate the effect of DOF extracts on neurotrophic factor synthesis, EACA (plasminogen inhibitor, 5.0 mM) and JNJ0966 (MMP-9 inhibitor, 0.4 μM) were used to treat astrocytes for 24 hrs before exposure to DOF extracts (Humphries, Vasudevan, & Gonias, 1993). PC12 cell lines were used to evaluate the ability of DOF extracts to promote neuronal differentiation.…”