Stimulation of Endothelin B Receptors in Astrocytes Induces cAMP Response Element-Binding Protein Phosphorylation and<i>c-fos</i>Expression Via Multiple Mitogen-Activated Protein Kinase Signaling Pathways

Schinelli, Sergio; Zanassi, Patrizia; Paolillo, Mayra; Wang, Hang; Feliciello, Antonio; Gallo, Vittorio

doi:10.1523/jneurosci.21-22-08842.2001

Cited by 94 publications

(90 citation statements)

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“…This can be explained by the report that CREB-dependent genes may also be activated by the MAPK and phosphoinositide 3-kinase signaling pathways independent of Ca 2ϩ signaling (57). Likewise, Shaywitz and Greenberg (58) have demonstrated that a variety of kinase signaling pathways can differentially contribute to Ca 2ϩ influx-mediated phosphorylation of CREB in pheochromocytoma (PC12) cells.…”

Section: Discussionmentioning

confidence: 99%

The Extracellular Signal-regulated Kinase Mitogen-activated Protein Kinase/Ribosomal S6 Protein Kinase 1 Cascade Phosphorylates cAMP Response Element-binding Protein to Induce MUC5B Gene Expression via d-Prostanoid Receptor Signaling

Choi

Lee

Aoyagi

et al. 2011

Journal of Biological Chemistry

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Mucus hypersecretion is a prominent feature of respiratory diseases, and MUC5B is a major airway mucin. Mucin gene expression can be affected by inflammatory mediators, including prostaglandin (PG) D 2, an inflammatory mediator synthesized by hematopoietic PGD synthase (H-PGDS). PGD 2 binds to either D-prostanoid receptor (DP1) or chemoattractant receptor homologous molecule expressed on T-helper type 2 cells (CRTH2). We investigated the mechanisms by which PGD 2 induces MUC5B gene expression in airway epithelial cells. Western blot analysis showed that H-PGDS was highly expressed in nasal polyps. Similar results were obtained for PGD 2 expression. In addition, we could clearly detect the expressions of both H-PGDS and DP1 in nasal epithelial cells but not CRTH2. We demonstrated that PGD 2 increased MUC5B gene expression in normal human nasal epithelial cells as well as in NCI-H292 cells in vitro. S5751, a DP1 antagonist, inhibited PGD 2 -induced MUC5B expression, whereas a CRTH2 antagonist (OC0459) did not. These data suggest that PGD 2 induced MUC5B expression via DP1. Pretreatment with extracellular signal-regulated kinase (ERK) inhibitor (PD98059) blocked both PGD 2 -induced ERK mitogen-activated protein kinase (MAPK) activation and MUC5B expression. Proximity ligation assays showed direct interaction between RSK1 and cAMP response element-binding protein (CREB). Stimulation with PGD 2 caused an increase in intracellular cAMP levels, whereas intracellular Ca 2؉ did not have such an effect. PGD 2 -induced MUC5B mRNA levels were regulated by CREB via direct interaction with two cAMP-response element sites (؊921/؊914 and ؊900/؊893). Finally, we demonstrated that PGD 2 can induce MUC5B overproduction via ERK MAPK/ RSK1/CREB signaling and that DP1 receptor may have suppressive effects in controlling MUC5B overproduction in the airway.Mucus secretion in the airway, including the nasal and paranasal sinus cavities, is drained by the mucociliary transport system (1). Normal mucus secretion is essential for survival (2), but upregulation of mucin gene expression is a major manifestation of chronic airway diseases such as allergic rhinitis, asthma, and cystic fibrosis (3, 4). Patients suffering from these diseases have pathological abnormalities in both the submucosal glands and surface epithelium, characterized by inflammation, increased mucus cell number, and increased airway mucus. Several classes of inflammatory mediators have been implicated in the process of mucus hypersecretion based on their ability to stimulate secretion from cultured cells and tissue explants (5). These inflammatory mediators are lipopolysaccharides (6), reactive oxygen species (7), and arachidonic acid metabolites (8, 9).A total of 20 different mucin genes have been identified and subdivided into two groups, membrane-bound and secreted mucins, according to Human Genome Mapping conventions. The secreted mucins are MUC5AC, MUC5B, MUC6, and MUC19 (10 -13). Mucins are primarily synthesized by two different cell types in the airway tract, namely...

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Section: Discussionmentioning

confidence: 99%

The Extracellular Signal-regulated Kinase Mitogen-activated Protein Kinase/Ribosomal S6 Protein Kinase 1 Cascade Phosphorylates cAMP Response Element-binding Protein to Induce MUC5B Gene Expression via d-Prostanoid Receptor Signaling

Choi

Lee

Aoyagi

et al. 2011

Journal of Biological Chemistry

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“…It has been shown previously that mitogenactivated protein kinase (MAPK) cascades drive the cell cycle through G1, at least in part through modulation of expression of cyclin D1 (Lavoie et al, 1996). Further, it has also been shown that ERKs can affect the expression of CDK inhibitors such as p21 cip1 and p27 kip1 leading to their accumulation and G1 arrest (Kawada et al, 1997;Woods et al, 1997;Schinelli et al, 2001). It is unclear from our results the primary effect of expression of RPS6KA2; whether there is a direct effect on ERK activity or through some negative feedback.…”

Section: Discussionmentioning

confidence: 99%

RPS6KA2, a putative tumour suppressor gene at 6q27 in sporadic epithelial ovarian cancer

et al. 2006

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We had previously defined by allele loss studies a minimal region at 6q27 (between D6S264 and D6S297) to contain a putative tumour suppressor gene. The p90 ribosomal S6 kinase-3 gene (p90 Rsk-3, RPS6KA2) maps in this interval. It is a serine-threonine kinase that signals downstream of the mitogen-activated protein kinase pathway. It is expressed in normal ovarian epithelium, whereas reduced or absent in tumours or cell lines. We show that RPS6KA2 is monoallelically expressed in the ovary suggesting that loss of a single expressed allele is sufficient to cause complete loss of expression in cancer cells. Further, we have identified two new isoforms of RPS6KA2 with an alternative start codon. Homozygous deletions were identified within the RPS6KA2 gene in two cell lines. Re-expression of RPS6KA2 in ovarian cancer cell lines suppressed colony formation. In UCI101 cells, the expression of RPS6KA2 reduced proliferation, caused G1 arrest, increased apoptosis, reduced levels of phosphorylated extracellular signal-regulated kinase and altered other cell cycle proteins. In contrast, small interfering RNA against RPS6KA2 showed the opposite effect in 41M cells. The above results suggest that RPS6KA2 is a putative tumour suppressor gene to explain allele loss at 6q27.

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“…Purified astrocyte cultures were prepared from 20-day-old Sprague-Dawley rat embryos. Cortices were dissected and then mechanically dissociated as described (35). The cultures comprise Ͼ95% GFAP-positive cells (35).…”

Section: Methodsmentioning

confidence: 99%

“…Cortices were dissected and then mechanically dissociated as described (35). The cultures comprise Ͼ95% GFAP-positive cells (35). For detailed information, see Supporting Materials and Methods.…”

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

Cell cycle inhibition provides neuroprotection and reduces glial proliferation and scar formation after traumatic brain injury

Giovanni

Movsesyan²,

Ahmed³

et al. 2005

Proc. Natl. Acad. Sci. U.S.A.

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350

311

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Traumatic brain injury (TBI) causes neuronal apoptosis, inflammation, and reactive astrogliosis, which contribute to secondary tissue loss, impaired regeneration, and associated functional disabilities. Here, we show that up-regulation of cell cycle components is associated with caspase-mediated neuronal apoptosis and glial proliferation after TBI in rats. In primary neuronal and astrocyte cultures, cell cycle inhibition (including the cyclin-dependent kinase inhibitors flavopiridol, roscovitine, and olomoucine) reduced upregulation of cell cycle proteins, limited neuronal cell death after etoposide-induced DNA damage, and attenuated astrocyte proliferation. After TBI in rats, flavopiridol reduced cyclin D1 expression in neurons and glia in ipsilateral cortex and hippocampus. Treatment also decreased neuronal cell death and lesion volume, reduced astroglial scar formation and microglial activation, and improved motor and cognitive recovery. The ability of cell cycle inhibition to decrease both neuronal cell death and reactive gliosis after experimental TBI suggests that this treatment approach may be useful clinically.flavopiridol ͉ glial scar ͉ neuron ͉ trauma

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Stimulation of Endothelin B Receptors in Astrocytes Induces cAMP Response Element-Binding Protein Phosphorylation andc-fosExpression Via Multiple Mitogen-Activated Protein Kinase Signaling Pathways

Cited by 94 publications

References 50 publications

The Extracellular Signal-regulated Kinase Mitogen-activated Protein Kinase/Ribosomal S6 Protein Kinase 1 Cascade Phosphorylates cAMP Response Element-binding Protein to Induce MUC5B Gene Expression via d-Prostanoid Receptor Signaling

The Extracellular Signal-regulated Kinase Mitogen-activated Protein Kinase/Ribosomal S6 Protein Kinase 1 Cascade Phosphorylates cAMP Response Element-binding Protein to Induce MUC5B Gene Expression via d-Prostanoid Receptor Signaling

RPS6KA2, a putative tumour suppressor gene at 6q27 in sporadic epithelial ovarian cancer

Cell cycle inhibition provides neuroprotection and reduces glial proliferation and scar formation after traumatic brain injury

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