Expression of protease-activated receptors (PARs) in OLN-93 oligodendroglial cells and mechanism of PAR-1-induced calcium signaling

Wang, Yingfei; Richter‐Landsberg, Christiane; Reiser, Georg

doi:10.1016/j.neuroscience.2004.03.024

Cited by 38 publications

(23 citation statements)

References 53 publications

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“…The thrombin receptor PAR‐1 is present on cells from the OLN‐93 oligodendrocyte cell line as well as rat primary oligodendrocytes in culture. Thrombin stimulates a Ca 2+ response through that receptor (Wang et al. 2004).…”

Section: Discussionmentioning

confidence: 99%

“…Down‐regulation of PAR‐1 mRNA following exposure to plasma could represent an attempt to reduce the signaling effect. Clarification of the role of thrombin using downstream signaling analysis, PAR‐1 knockdown experiments by RNA silencing, use of PAR‐1 peptide antagonists (Wang et al. 2004), or by studying cells from PAR‐1 knockout mice (Darrow et al.…”

Section: Discussionmentioning

confidence: 99%

“…Because thrombin appeared to be playing a role in the cell death, we studied the expression of the mRNA for thrombin receptor (protease activated receptor, PAR‐1) (Wang et al. 2004).…”

Section: Methodsmentioning

confidence: 99%

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Toxic effect of blood components on perinatal rat subventricular zone cells and oligodendrocyte precursor cell proliferation, differentiation and migration in culture

Juliet

Frost

Balasubramaniam

et al. 2009

Journal of Neurochemistry

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The germinal matrix of human brain gives rise to oligodendrocytes and astrocytes after mid‐gestation. Hemorrhage in the germinal matrix of premature infants is associated with suppressed cell proliferation. We hypothesize that soluble blood constituents have an adverse effect on the proliferation of cultured rat subventricular zone (SVZ) cells and the proliferation, migration, and differentiation of oligodendrocyte progenitor cells (OPC). Using caspase 3 activation and lactate dehydrogenase release assays, rat plasma, serum, thrombin, and kallikrein killed SVZ cells when grown in the presence (but not absence) of platelet derived growth factor. Plasma and serum killed OPC at 1 : 1 to 1 : 100 dilutions. Using a bromodeoxyuridine incorporation assay OPC proliferation was reduced by plasma, serum, thrombin and plasmin. Blood proteins also suppressed OPC migration in a concentration dependent manner. However, differentiation of OPC into myelin basic protein expressing cells was suppressed only by thrombin. We conclude that soluble blood components, particularly thrombin, have an adverse effect on maturing SVZ cells and OPC derived from newborn rat brain.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Toxic effect of blood components on perinatal rat subventricular zone cells and oligodendrocyte precursor cell proliferation, differentiation and migration in culture

Juliet

Frost

Balasubramaniam

et al. 2009

Journal of Neurochemistry

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“…PAR1 activation has been linked to astrocyte reactivity (Nicole et al 2005; Scarisbrick et al 2012a) and thrombin-induced neurotoxicity (Striggow et al 2000). PAR1 is already known to be expressed by oligodendroglia (Wang et al 2004b) and here we examine its potential role in oligodendrocyte pathophysiology.…”

Section: Introductionmentioning

confidence: 99%

Critical role for PAR1 in kallikrein 6‐mediated oligodendrogliopathy

Burda¹,

Radulovic²,

Yoon

et al. 2013

Glia

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Kallikrein 6 (Klk6) is a secreted serine protease preferentially expressed by oligodendroglia in CNS white matter. Elevated levels of Klk6 occur in actively demyelinating multiple sclerosis (MS) lesions and in cases of spinal cord injury (SCI), stroke and glioblastoma. Taken with recent evidence establishing Klk6 as a CNS-endogenous activator of protease-activated receptors (PARs), we hypothesized that Klk6 activates a subset of PARs to regulate oligodendrocyte physiology and potentially pathophysiology. Here, primary oligodendrocyte cultures derived from wild type or PAR1-deficient mice and the murine oligodendrocyte cell line, Oli-neu, were used to demonstrate that Klk6 mediates loss of oligodendrocyte processes and impedes morphological differentiation of oligodendrocyte progenitor cells (OPCs) in a PAR1-dependent fashion. Comparable gliopathy was also elicited by the canonical PAR1 agonist, thrombin, as well as PAR1-activating peptides (PAR1-APs). Klk6 also exacerbated ATP-mediated oligodendrogliopathy in vitro, pointing to a potential role in augmenting excitotoxicity. In addition, Klk6 suppressed the expression of proteolipid protein (PLP) RNA in cultured oligodendrocytes by a mechanism involving PAR1-mediated Erk1/2 signaling. Microinjection of PAR1 agonists, including Klk6 or PAR1-APs, into the dorsal column white matter of PAR+/+ but not PAR−/− mice promoted vacuolating myelopathy and a loss of immunoreactivity for myelin basic protein (MBP) and CC-1+ oligodendrocytes. These results demonstrate a functional role for Klk6-PAR1 signaling in oligodendroglial pathophysiology and suggest that PAR1 or PAR1-agonists may represent new targets to moderate demyelination and to promote myelin regeneration in cases of CNS white matter injury or disease.

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“…All members are widely expressed in the CNS by neurons, microglia, astrocytes, and oligodendrocytes, and are possible therapeutic targets for the treatment of neurodegenerative disorders [8-12]. Under pathological conditions, PARs have been shown to mediate either neuronal death or survival.…”

Section: Introductionmentioning

confidence: 99%

Transient early neurotrophin release and delayed inflammatory cytokine release by microglia in response to PAR-2 stimulation

Chen

Ouyang

et al. 2012

J Neuroinflammation

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Activated microglia exerts both beneficial and deleterious effects on neurons, but the signaling mechanism controlling these distinct responses remain unclear. We demonstrated that treatment of microglial cultures with the PAR-2 agonist, 2-Furoyl-LIGRLO-NH2, evoked early transient release of BDNF, while sustained PAR-2 stimulation evoked the delayed release of inflammatory cytokines (IL-1β and TNF-α) and nitric oxide. Culture medium harvested during the early phase (at 1 h) of microglial activation induced by 2-Furoyl-LIGRLO-NH2 (microglial conditioned medium, MCM) had no deleterious effects on cultured neurons, while MCM harvested during the late phase (at 72 h) promoted DNA fragmentation and apoptosis as indicated by TUNEL and annexin/PI staining. Blockade of PAR-1 during the early phase of PAR-2 stimulation enhanced BDNF release (by 11%, small but significant) while a PAR-1 agonist added during the late phase (24 h after 2-Furoyl-LIGRLO-NH2 addition) suppressed the release of cytokines and NO. The neuroprotective and neurotoxic effects of activated microglial exhibit distinct temporal profiles that are regulated by PAR-1 and PAR-2 stimulation. It may be possible to facilitate neuronal recovery and repair by appropriately timed stimulation and inhibition of microglial PAR-1 and PAR-2 receptors.

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Expression of protease-activated receptors (PARs) in OLN-93 oligodendroglial cells and mechanism of PAR-1-induced calcium signaling

Cited by 38 publications

References 53 publications

Toxic effect of blood components on perinatal rat subventricular zone cells and oligodendrocyte precursor cell proliferation, differentiation and migration in culture

Toxic effect of blood components on perinatal rat subventricular zone cells and oligodendrocyte precursor cell proliferation, differentiation and migration in culture

Critical role for PAR1 in kallikrein 6‐mediated oligodendrogliopathy

Transient early neurotrophin release and delayed inflammatory cytokine release by microglia in response to PAR-2 stimulation

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