Characterization of astrocyte plasminogen activator

Toshniwal, Pradip K.; Firestone, Susan; Barlow, Grant H.; Tiku, M. L.

doi:10.1016/0022-510x(87)90162-6

Cited by 17 publications

(11 citation statements)

References 27 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…tPA, which influences neurite outgrowth, is expressed by many types of neural cells in the developing brain, including astrocytes [42]. Treatment of primary cortical neurons with an antibody against tPA significantly reduced neurite outgrowth and branch numbers compared to control neurons without tPA treatment.…”

Section: Discussionmentioning

confidence: 97%

Increasing tPA Activity in Astrocytes Induced by Multipotent Mesenchymal Stromal Cells Facilitate Neurite Outgrowth after Stroke in the Mouse

et al. 2010

View full text Add to dashboard Cite

We demonstrate that tissue plasminogen activator (tPA) and its inhibitors contribute to neurite outgrowth in the central nervous system (CNS) after treatment of stroke with multipotent mesenchymal stromal cells (MSCs). In vivo, administration of MSCs to mice subjected to middle cerebral artery occlusion (MCAo) significantly increased activation of tPA and downregulated PAI-1 levels in the ischemic boundary zone (IBZ) compared with control PBS treated mice, concurrently with increases of myelinated axons and synaptophysin. In vitro, MSCs significantly increased tPA levels and concomitantly reduced plasminogen activator inhibitor 1 (PAI-1) expression in astrocytes under normal and oxygen and glucose deprivation (OGD) conditions. ELISA analysis of conditioned medium revealed that MSCs stimulated astrocytes to secrete tPA. When primary cortical neurons were cultured in the conditioned medium from MSC co-cultured astrocytes, these neurons exhibited a significant increase in neurite outgrowth compared to conditioned medium from astrocytes alone. Blockage of tPA with a neutralizing antibody or knock-down of tPA with siRNA significantly attenuated the effect of the conditioned medium on neurite outgrowth. Addition of recombinant human tPA into cortical neuronal cultures also substantially enhanced neurite outgrowth. Collectively, these in vivo and in vitro data suggest that the MSC mediated increased activation of tPA in astrocytes promotes neurite outgrowth after stroke.

show abstract

Section: Discussionmentioning

confidence: 97%

Increasing tPA Activity in Astrocytes Induced by Multipotent Mesenchymal Stromal Cells Facilitate Neurite Outgrowth after Stroke in the Mouse

et al. 2010

View full text Add to dashboard Cite

show abstract

“…In line with endotoxin induced increased PA-PAI-1 activity, endotoxin upregulates PAI-1 mRNA expression in a timedependent manner. Previous studies have shown tPA (Toshniwal et al, 1987) and uPA (Tranque et al, 1992) production by astroglial cells (Goldberg et al, 1992). This may relate to findings demonstrating that production of uPA by astroglial cells was only found in immature astroglial cells, and it disappears at later stages, while tPA persists (Kalderon et al, 1990).…”

Section: Discussionmentioning

confidence: 71%

“…PAI-1 belongs to a family of serine protease inhibitors (serpins) and forms a tight complex with PA that has no PA activity (Sprengers and Kluft, 1987). Production of PA and PAI by astroglial cells is thought to be involved in myelination and myelin degeneration, cell migration, and regulation of plasticity in the central nervous system (CNS) (Toshniwal et al, 1987). We are interested if PA are important in the activation of latent TGF␤ which inhibits NO production by microglial cells.…”

Section: Introductionmentioning

confidence: 99%

Role of astrocyte-derived tissue-type plasminogen activator in the regulation of endotoxin-stimulated nitric oxide production by microglial cells

Vincent

Löwik

Verheijen³

et al. 1998

Glia

View full text Add to dashboard Cite

In mixed glial cell cultures from cerebral cortices of newborn rats, endotoxin induces nitric oxide (NO) production in microglial cells. Earlier we demonstrated that endotoxin induced NO production by microglial cells is inhibited in the presence of astroglial cells by transforming growth factor β (TGFβ). Both microglial and astroglial cells produce TGFβ in a biologically inactive form, which can be activated by plasmin generated by plasminogen activators (PA). In the present paper we describe studies on the mechanism by which glial cells may activate inactive TGFβ and its potential inhibitory effect on NO production by microglial cells. Inhibition of plasmin increased NO production in endotoxin‐treated mixed glial cell cultures. Subsequently, antibodies against tissue‐type plasminogen activator (tPA) increased NO production in endotoxin‐treated mixed glial cell cultures while amiloride, an inhibitor for urokinase (uPA), had no effect. We hereby concluded that tPA is the crucial PA involved in plasmin production resulting in inhibition of NO production in mixed glial cell cultures. Zymography and Northern blot analysis of purified astroglial, microglial, and mixed glial cell cultures demonstrated that astroglial cells produce tPA and a plasminogen activator inhibitor (PAI‐1) and are thereby responsible for the production of plasmin which may activate the inactive TGFβ in these cultures. In conclusion, astroglial‐derived tPA plays a major role in the inhibition of NO production by endotoxin‐treated microglial cells through enhanced plasmin production and possible subsequent TGFβ activation. GLIA 22:130–137, 1998. © 1998 Wiley‐Liss, Inc.

show abstract

“…41 Physical exercise and certain vasoactive substances produce measurable increases in circulating t-PA levels, and 1-deamino(8-D-arginine) vasopressin (DDAVP) may produce a 3-4-fold increase in t-PA antigen levels within 60 minutes of parenteral infusion in some patients. 18,[42][43][44][45][46][47] The reasons for this broad cell expression are not known, however. 18,[42][43][44][45][46][47] The reasons for this broad cell expression are not known, however.…”

Section: Tissue-type Plasminogen Activatormentioning

confidence: 99%

“…The inactive gelatinases pro-MMP-2 and pro-MMP-9 are released from vascular endothelium, leukocytes, and other cells during inflammation; pro-MMP-2 is activated by membrane-bound MT1-and Wistar-Kyoto rats, and primates. [42][43][44][45][46][47] u-PA mRNA is expressed in neurons and oligodendrocytes during process outgrowth in the rodent brain. 46 Tissue-type PA and u-PA are secreted by endothelial cells, neurons, astrocytes, and microglia in vivo or in vitro.…”

Section: Plasminogen Activators and Cerebral Microvessel Integritymentioning

confidence: 99%

Mechanisms of Thrombosis and Thrombolysis

Zoppo¹

2016

Stroke

View full text Add to dashboard Cite

Characterization of astrocyte plasminogen activator

Cited by 17 publications

References 27 publications

Increasing tPA Activity in Astrocytes Induced by Multipotent Mesenchymal Stromal Cells Facilitate Neurite Outgrowth after Stroke in the Mouse

Increasing tPA Activity in Astrocytes Induced by Multipotent Mesenchymal Stromal Cells Facilitate Neurite Outgrowth after Stroke in the Mouse

Role of astrocyte-derived tissue-type plasminogen activator in the regulation of endotoxin-stimulated nitric oxide production by microglial cells

Mechanisms of Thrombosis and Thrombolysis

Contact Info

Product

Resources

About