Plasminogen activators and inhibitors in the neuromuscular system: III. The serpin protease nexin I is synthesized by muscle and localized at neuromuscular synapses

1991 ◽  
Vol 147 (1) ◽  
pp. 76-86 ◽  
Author(s):  
B. W. Festoff ◽  
J. S. Rao ◽  
D. Hantaï
Keyword(s):  
Plasminogen Activators ◽  
Neuromuscular System ◽  
Neuromuscular Synapses ◽  
Protease Nexin

Expression of mRNA for plasminogen activators and protease nexin-1 in innervated and denervated mouse skeletal muscle

2001 ◽  
Vol 66 (3) ◽  
pp. 457-463 ◽  
Author(s):  
Caroline Magnusson ◽  
Lars Högklint ◽  
Rolf Libelius ◽  
Sven Tågerud
Keyword(s):  
Skeletal Muscle ◽  
Plasminogen Activators ◽  
Mouse Skeletal Muscle ◽  
Protease Nexin

Plasminogen activators in the neuromuscular system of the wobbler mutant mouse

1992 ◽  
Vol 580 (1-2) ◽  
pp. 303-310 ◽  
Author(s):  
Brigitte Blondet ◽  
Georgia Barlovatz-Meimon ◽  
Barry W. Festoff ◽  
Claudine Soria ◽  
Jeannette Soria ◽  
...  
Keyword(s):  
Mutant Mouse ◽  
Plasminogen Activators ◽  
Neuromuscular System

scholarly journals Emerging role of serpinE2/protease nexin-1 in hemostasis and vascular biology

Blood ◽  
2012 ◽  
Vol 119 (11) ◽  
pp. 2452-2457 ◽  
Author(s):  
Marie-Christine Bouton ◽  
Yacine Boulaftali ◽  
Benjamin Richard ◽  
Véronique Arocas ◽  
Jean-Baptiste Michel ◽  
...  
Keyword(s):  
Treatment Strategies ◽  
Vascular Biology ◽  
Cell Types ◽  
Plasminogen Activators ◽  
Key Factor ◽  
Nervous System Function ◽  
Heparan Sulfates ◽  
Protease Nexin ◽  
Deficient Mice

Abstract Serine protease inhibitors, termed serpins, are key regulators in many biologic events. Protease nexin-1 (PN-1) is a serpin that is barely detectable in plasma but found in many organs and produced by most cell types, including monocytes, platelets, and vascular cells. It has a large inhibition spectrum because it is the most efficient tissue inhibitor of thrombin but also a powerful inhibitor of plasminogen activators and plasmin. It has a high affinity for glycosaminoglycans, such as heparan sulfates, which potentiate its activity toward thrombin and target it to the pericellular space. PN-1 has been previously largely described as a crucial regulator of the proteolytic activity in nerves and of central and peripheral nervous system function. In contrast, little was known about its involvement in hemostasis and vascular biology. This article reviews recent data underlining its emerging role as a key factor in the responses of vessels to injury. Indeed, studies of PN-1–deficient mice have established important antithrombotic and antifibrinolytic properties of this serpin that have heretofore gone unrecognized. The roles of PN-1 in the areas of hemostasis and thrombosis summarized here provide insights that may allow the development of drugs and treatment strategies to prevent or limit thrombotic disorders.

scholarly journals Expression of protease nexin-1 and plasminogen activators during follicular growth and the periovulatory period in cattle

Reproduction ◽  
2006 ◽  
Vol 131 (1) ◽  
pp. 125-137 ◽  
Author(s):  
Mingju Cao ◽  
José Buratini ◽  
Jacques G Lussier ◽  
Paul D Carrière ◽  
Christopher A Price
Keyword(s):  
Follicular Development ◽  
Plasminogen Activators ◽  
Tissue Type ◽  
Matrix Remodeling ◽  
Mrna Levels ◽  
Plasmin Activity ◽  
Expected Time ◽  
Follicular Wave ◽  
Protease Nexin ◽  
Pai 1

Extracellular matrix remodeling occurs during ovarian follicular development, mediated by plasminogen activators (PAs) and PA inhibitors including protease nexin-1 (PN-1). In the present study we measured expression/activity of the PA system in bovine follicles at different stages of development by timed collection of ovaries during the first follicular wave and during the periovulatory period, and in follicles collected from an abattoir. The abundance of mRNA encoding PN-1, tissue-type PA (tPA), urokinase (uPA) and PA inhibitor-1 (PAI-1) were initially upregulated by human chorionic gonadotropin (hCG) in bovine preovulatory follicular wall homogenates. PN-1, PAI-1 and tPA mRNA expression then decreased near the expected time of ovulation, whereas uPA mRNA levels remained high. PN-1 concentration in follicular fluid (FF) decreased and reached the lowest level at the time of ovulation, whereas plasmin activity in FF increased significantly after hCG. Follicles collected from the abattoir were classified as non-atretic, early-atretic or atretic based on FF estradiol and progesterone content: PN-1 protein levels in FF were significantly higher in non-atretic than in atretic follicles, and plasmin activity was correspondingly higher in the atretic follicles. No changes in PN-1 levels in FF were observed during the growth of pre-deviation follicles early in a follicular wave. These results indicate that PN-1 may be involved in the process of atresia in non-ovulatory dominant follicles and the prevention of precocious proteolysis in periovulatory follicles.

scholarly journals Functional limb muscle innervation prior to cholinergic transmitter specification during early metamorphosis in Xenopus

eLife ◽  
2018 ◽  
Vol 7 ◽  
Author(s):  
Francois M Lambert ◽  
Laura Cardoit ◽  
Elric Courty ◽  
Marion Bougerol ◽  
Muriel Thoby-Brisson ◽  
...  
Keyword(s):  
Nicotinic Receptors ◽  
System Development ◽  
Neuromuscular System ◽  
Spinal Neurons ◽  
Neuromuscular Synapses ◽  
Hindlimb Muscles ◽  
Peripheral Muscle ◽  
Glutamate Antagonist ◽  
Muscle Innervation ◽  
Functional Limb

In vertebrates, functional motoneurons are defined as differentiated neurons that are connected to a central premotor network and activate peripheral muscle using acetylcholine. Generally, motoneurons and muscles develop simultaneously during embryogenesis. However, during Xenopus metamorphosis, developing limb motoneurons must reach their target muscles through the already established larval cholinergic axial neuromuscular system. Here, we demonstrate that at metamorphosis onset, spinal neurons retrogradely labeled from the emerging hindlimbs initially express neither choline acetyltransferase nor vesicular acetylcholine transporter. Nevertheless, they are positive for the motoneuronal transcription factor Islet1/2 and exhibit intrinsic and axial locomotor-driven electrophysiological activity. Moreover, the early appendicular motoneurons activate developing limb muscles via nicotinic antagonist-resistant, glutamate antagonist-sensitive, neuromuscular synapses. Coincidently, the hindlimb muscles transiently express glutamate, but not nicotinic receptors. Subsequently, both pre- and postsynaptic neuromuscular partners switch definitively to typical cholinergic transmitter signaling. Thus, our results demonstrate a novel context-dependent re-specification of neurotransmitter phenotype during neuromuscular system development.

scholarly journals Functional limb muscle innervation prior to cholinergic transmitter specification during early metamorphosis in Xenopus

2017 ◽  
Author(s):  
F. M. Lambert ◽  
L. Cardoit ◽  
E. Courty ◽  
M. Bougerol ◽  
M. Thoby-Brisson ◽  
...  
Keyword(s):  
Nicotinic Receptors ◽  
System Development ◽  
Neuromuscular System ◽  
Spinal Neurons ◽  
Neuromuscular Synapses ◽  
Hindlimb Muscles ◽  
Peripheral Muscle ◽  
Glutamate Antagonist ◽  
Muscle Innervation ◽  
Functional Limb

ABSTRACTIn vertebrates, functional motoneurons are defined as differentiated neurons that are connected to a central premotor network and activate peripheral muscle using acetylcholine. Generally, motoneurons and muscles develop simultaneously during embryogenesis. However, during Xenopus metamorphosis, developing limb motoneurons must reach their target muscles through the already established larval cholinergic axial neuromuscular system. Here, we demonstrate that at metamorphosis onset, spinal neurons retrogradely labeled from the emerging hindlimbs initially express neither choline acetyltransferase nor vesicular acetylcholine transporter. Nevertheless, they are positive for the motoneuronal transcription factor Islet1/2 and exhibit intrinsic and axial locomotor-driven electrophysiological activity. Moreover, the early appendicular motoneurons activate developing limb muscles via nicotinic antagonist-resistant, glutamate antagonist-sensitive, neuromuscular synapses. Coincidently, the hindlimb muscles transiently express glutamate, but not nicotinic receptors. Subsequently, both pre- and postsynaptic neuromuscular partners switch definitively to typical cholinergic transmitter signaling. Thus, our results demonstrate a novel context-dependent re-specification of neurotransmitter phenotype during neuromuscular system development.

scholarly journals Platelet Protease Nexin-1, a Serpin That Strongly Influences Fibrinolysis and Thrombolysis

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 818-818
Author(s):  
Yacine Boulaftali ◽  
Benoit Ho-Tin-Noe ◽  
Ana Pena ◽  
Stéphane Loyau ◽  
Laurence Venisse ◽  
...  
Keyword(s):  
Thrombus Formation ◽  
Plasminogen Activators ◽  
Tissue Type ◽  
Dorsal Skinfold Chamber ◽  
Protease Nexin ◽  
Deficient Mice ◽  
Pai 1

Abstract Abstract 818 Fibrinolysis, a physiological process leading to clot resorbtion, is strictly controlled by fibrin-localized plasminogen activators (tPA and uPA) and by inhibitors like plasminogen activator type-1 (PAI-1). The serpin PAI-1 is a plasmatic serine protease inhibitor, that is also stored in platelets α-granules. PAI-1 inhibits both the action of urokinase- and tissue-type plasminogen activators (uPA and tPA respectively), and is up to now considered as the principal inhibitor of fibrinolysis in vivo. Interestingly, platelets are also known to inhibit fibrinolysis by both PAI-1-dependent and PAI-1-independent mechanisms. The individual role of other serpins, specifically protease nexin-1 (PN-1) in the thrombolytic process has not been investigated so far. Indeed, we recently demonstrated that a significant amount of PN-1 is stored within the α-granules of platelets and plays an antithrombotic function in vivo. PN-1, also known as SERPINE2, deserves a special interest since it also significantly inhibits in vitro uPA, tPA and plasmin. In this study, we explored the effect of PN-1 on fibrinolysis in vitro and in vivo. We evidenced the antifibrinolytic activity of platelet PN-1 in vitro using a specific PN-1-blocking antibody and PN-1 deficient platelets and, in vivo in PN-1−/− mice. Our data directly indicate that platelet PN-1 inhibits both tPA and plasmin activities in fibrin zymography. Remarkably, whereas fibrin-bound tPA or plasmin activity is not affected by PAI-1, we showed that PN-1 inhibits both plasmin generation induced by tPA-bound to fibrin and fibrin-bound plasmin. Moreover, PN-1 blockade or PN-1 deficiency result in an increased lysis of fibrin clots generated from platelet-rich plasma indicating that PN-1 regulates endogenous tPA-mediated lysis. Rotational thromboelastometry (ROTEM®) analysis shows that platelet PN-1 significantly decreases the rate of fibrinolysis ex vivo. Futhermore, blockade or deficiency of PN-1 provides direct evidence for an acceleration of the lysis-front velocity in platelet-rich clots. To challenge the role of PN-1 on fibrinolysis in vivo, we have developed an original murine model of thrombolysis. Using a dorsal skinfold chamber, thrombus formation induced by ferric chloride injury of venules and subsequent thrombolysis were visualized by microscopy on alive animals. This new approach allows a reproducible quantification of thrombus formation and of tPA- induced thrombus lysis. We observed that thrombi are more readily lysed in PN-1-deficient mice than in wild-type mice. Moreover, in PN-1 deficient mice, the rate and the extent of reperfusion were both increased (Figure A and B). These data demonstrate that platelet PN-1 is a new negative regulator of thrombolysis activity of plasmin, both in solution and within the clot. For the first time, this study shows that PN-1 protects towards thrombolysis and therefore could give rise to new approaches for therapeutic application. Indeed, PN-1 might be a promising target for optimizing thrombolytic therapy by tPA. Figure : Effect of PN-1 on thrombolysis. (A) Representative intravital images of vessels reperfusion after tPA treatment in dorsal skinfold chamber. (B) Quantification of the incidence of reperfused vessels within 1 hour post tPA treatment Figure :. Effect of PN-1 on thrombolysis. (A) Representative intravital images of vessels reperfusion after tPA treatment in dorsal skinfold chamber. (B) Quantification of the incidence of reperfused vessels within 1 hour post tPA treatment Disclosures: No relevant conflicts of interest to declare.

Plasminogen Activators in Development, Injury and Pathology of the Neuromuscular System

1990 ◽  
pp. 219-228 ◽  
Author(s):  
Daniel Hantaï ◽  
Claudine Soria ◽  
Jeannette Soria ◽  
Brigitte Blondet ◽  
Georgia Barlovatz-Meimon ◽  
...  
Keyword(s):  
Plasminogen Activators ◽  
Neuromuscular System
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