Prevention of activity-dependent neuronal death: Vasoactive intestinal polypeptide stimulates astrocytes to secrete the thrombin-inhibiting neurotrophic serpin, protease nexin I

Festoff, Barry W.; Nelson, Phillip G.; Brenneman, Douglas E.

doi:10.1002/(sici)1097-4695(199606)30:2<255::aid-neu7>3.0.co;2-4

Cited by 89 publications

(54 citation statements)

References 65 publications

(74 reference statements)

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“…PN-1 is the most potent thrombin inhibitor in the brain, but it can also form complexes with plasmin, tissue, and urokinase plasminogen activators and trypsin (Reinhard et al, 1994;Gingrich and Traynelis, 2000). Apart from regulation by de novo biosynthesis (Vaughan and Cunningham, 1993), PN-1 secretion appears to be regulated by activated G-coupled receptors, such as VIP receptors (Festoff et al, 1996). Here, we show that activation of VPAC receptors coupled to heterotrimeric Gi/Go-proteins is able to control exocytosis of GFP/PN-1 in C6 glioma cells.…”

Section: Discussionmentioning

confidence: 99%

Constitutive Secretion of Protease Nexin-1 by Glial Cells and Its Regulation by G-Protein-Coupled Receptors

Giau¹,

Carrette²,

Bockaert³

et al. 2005

J. Neurosci.

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Extracellular serine proteases and their inhibitors (serpins) play a key role for synaptic plasticity in the developing and adult CNS. Serpins also counteract the extravasated proteases during brain injury. We studied the mechanisms by which one of the most important serpins, serpinE2 or protease nexin-1 (PN-1), is secreted by glial cells and how its secretion is regulated by extracellular signals. Using time-lapse videomicroscopy and biochemical methods, we demonstrate that PN-1 is constitutively secreted through small vesicles animated by a discontinuous movement using microtubules as tracks. The F-actin network underneath the plasma membrane acting as a barrier hindered PN-1 vesicle exocytosis. Vasointestinal/pituitary adenylate cyclase peptides and the G-protein activator mastoparan increased PN-1 secretion by disrupting the F-actin barrier. The receptor-mediated regulation of PN-1 constitutive secretion may be an important mechanism adapting extracellular proteolytic activity to synaptic activity.

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Section: Discussionmentioning

confidence: 99%

Constitutive Secretion of Protease Nexin-1 by Glial Cells and Its Regulation by G-Protein-Coupled Receptors

Giau¹,

Carrette²,

Bockaert³

et al. 2005

J. Neurosci.

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“…A number of roles for glial-produced serine proteases and protease inhibitors have been demonstrated. For example, astrocytederived PN I enhances the survival of mixed spinal neuron cultures (Festoff et al, 1996). Thrombin has been shown to induce the secretion of NGF from cultured astrocytes (Neveu et al, 1993) and to affect their proliferation and differentiation (Cavanaugh et al, 1990;Beecher et al, 1994).…”

Section: Region and Cell-specific Expression Of Msp In The Cnsmentioning

confidence: 99%

“…Transgenic mice deficient in tPA exhibit an altered form of long-term potentiation (Frey et al, 1996) and are resistant to excitotoxic-mediated neuronal degeneration (Tsirka et al, 1995(Tsirka et al, , 1997. Glial-derived protease nexin-I (PN I), a potent endogenous inhibitor of thrombin, specifically inhibits thrombin-induced neurite retraction Cunningham, 1988, 1990) and neuronal degeneration (Smith-Swintosky et al, 1995;Festoff et al, 1996). Additionally, PN I has been demonstrated to reduce axotomy-induced motor neuron death in the neonatal mouse and to prevent programmed cell death in the chick motor cell column when administered in ovo (Houenou et al, 1995).…”

mentioning

confidence: 99%

Nervous System-Specific Expression of a Novel Serine Protease: Regulation in the Adult Rat Spinal Cord by Excitotoxic Injury

1997

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A full-length cDNA clone of a previously unidentified serine protease, myelencephalon-specific protease (MSP), has been isolated by using a PCR cloning strategy and has been shown to be expressed in a nervous system and spinal cord-specific pattern. Sequence analysis demonstrated that MSP is most similar in sequence to neuropsin, trypsin, and tissue kallikrein and is predicted to have trypsin-like substrate specificity. MSP mRNA was found to be ϳ10-fold greater in the CNS of the rat and human, as compared with most peripheral tissues, and within the CNS was found to be highest by a factor of four in the medulla oblongata and spinal cord. Levels of mRNA encoding tissue plasminogen activator (tPA) also were elevated in the spinal cord but were more widespread in peripheral tissues as compared with MSP.In the adult rat lumbosacral spinal cord, in situ localization of MSP mRNA demonstrated 2-fold higher levels in the white, as compared with the gray, matter. MSP mRNA expression was shown to increase 3-fold in the white matter and 1.5-fold in the gray laminae at 72 hr after intraperitoneal injection of the AMPA/ kainate glutamate receptor-specific agonist, kainic acid (KA). MSP mRNA remained elevated in the ventral gray matter, including expression associated with the motor neurons of lamina IX, at 7 d after the initial excitotoxic insult. Together, these observations indicate that MSP is in a position to play a fundamental role in normal homeostasis and in the response of the spinal cord to injury.

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“…Protease expression is balanced by proteolytic inhibitors (Festoff et al, 1996;Osterwalder et al, 1996;Hastings et al, 1997;Jaworski and Fager, 2000;Hino et al, 2001;Kato et al, 2001). Given the neuronal roles of extracellular proteases and their inhibitors (Shiosaka and Yoshida, 2000), knowledge of their expression and regulation is critical to an understanding of neuronal communication, learning and memory, and certain instances of neuronal death.…”

mentioning

confidence: 99%

Localization and Regulation of the Tissue Plasminogen Activator–Plasmin System in the Hippocampus

2002

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The extracellular protease cascade of tissue plasminogen activator (tPA) and plasminogen has been implicated in neuronal plasticity and degeneration. We show here that unstimulated expression of tPA in the mouse hippocampus is concentrated in the mossy fiber pathway, with little or no expression within the perforant path, the Schaffer collaterals, or neuronal cell bodies. tPA protein is also expressed in vascular endothelial cells throughout the brain parenchyma. Four hours after excitotoxic injury, tPA protein is transiently induced within CA1 pyramidal neurons. The induced CA1 tPA is localized to neurons that survive the injury and is enzymatically active. Within the mossy fiber pathway, injury resulted in decreased tPA protein. In contrast, mossy fiber tPA activity displayed a biphasic character: transient increase at 8 hr, then a decrease by 24 hr after injury.Analysis of plasminogen activator inhibitor-1 (PAI-1) expression showed that PAI-1 antigen is upregulated by 24 hr and could account for the tPA activity downregulation seen at this time point. Plasminogen immunohistochemistry suggested an increase within the mossy fiber pathway after injury. Finally, hippocampal tPA expression among various mammalian species was strikingly different. These results indicate a complex control of tPA protein and enzymatic activity in the hippocampus that may help regulate neuronal plasticity.

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Prevention of activity-dependent neuronal death: Vasoactive intestinal polypeptide stimulates astrocytes to secrete the thrombin-inhibiting neurotrophic serpin, protease nexin I

Cited by 89 publications

References 65 publications

Constitutive Secretion of Protease Nexin-1 by Glial Cells and Its Regulation by G-Protein-Coupled Receptors

Constitutive Secretion of Protease Nexin-1 by Glial Cells and Its Regulation by G-Protein-Coupled Receptors

Nervous System-Specific Expression of a Novel Serine Protease: Regulation in the Adult Rat Spinal Cord by Excitotoxic Injury

Localization and Regulation of the Tissue Plasminogen Activator–Plasmin System in the Hippocampus

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