Elevated L-PGDS activity contributes to PMA-induced  apoptosis concomitant with downregulation of PI3-K

Ragolia, Louis; Palaia, Thomas; Paric, Enesa; Maesaka, John K.

doi:10.1152/ajpcell.00247.2002

Cited by 34 publications

(26 citation statements)

References 31 publications

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“…It is only when proliferation pathways are active that L-PGDS can induce apoptosis and inhibit cell proliferation. This is consistent with our previous findings in other cell lines, where L-PGDS-induced apoptosis is more pronounced in the presence of serum (19). In addition, L-PGDS pretreatment appears to inhibit insulin-stimulated proliferation by blocking any further Akt/GSK-3␤ phosphorylation in wild-type VSMCs (Figs.…”

Section: Figsupporting

confidence: 93%

“…We have also deter-mined that phorbol ester-induced apoptosis is mediated by L-PGDS phosphorylation and activation by protein kinase C, and is accompanied by an inhibition of the PI3K/PKB antiapoptotic signaling pathways (19). In the present study, we report on the elevation of L-PGDS in VSMCs isolated from SHR and the stimulation of enhanced L-PGDS production upon cell differentiation.…”

mentioning

confidence: 53%

“…Apoptotic Activity Assay-Apoptosis was quantitated as described previously (19) by the colorimetric measurement of caspase-3 activity as per the manufacturer's procedure. In addition, conformation of apoptosis was determined by TUNEL assay as described previously (19) using the ApopDetek Cell Death Assay Kit (Enzo, Farmingdale, NY).…”

Section: Methodsmentioning

confidence: 99%

“…In addition, conformation of apoptosis was determined by TUNEL assay as described previously (19) using the ApopDetek Cell Death Assay Kit (Enzo, Farmingdale, NY).…”

Section: Methodsmentioning

confidence: 99%

“…Previous work from this laboratory has linked both Akt and GSK-3␤ phosphorylation to L-PGDS-induced apoptosis (19). Insulin, a known inducer of Akt and GSK-3␤ phosphorylation, has been shown to stimulate proliferation and inhibit VSMC apoptosis (22).…”

Section: L-pgds Pretreatment Inhibits the Insulin-induced Phosphorylamentioning

confidence: 99%

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Prostaglandin D2 Synthase Inhibits the Exaggerated Growth Phenotype of Spontaneously Hypertensive Rat Vascular Smooth Muscle Cells

Ragolia

Palaia

Paric

et al. 2003

Journal of Biological Chemistry

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Lipocalin-type prostaglandin D 2 synthase (L-PGDS)has recently been linked to a variety of pathophysiological cardiovascular conditions including hypertension and diabetes. In this study, we report on the 50% increase in L-PGDS protein expression observed in vascular smooth muscle cells (VSMC) isolated from spontaneously hypertensive rats (SHR). L-PGDS expression also increased 50% upon the differentiation of normotensive control cells (WKY, from Wistar-Kyoto rats). In addition, we demonstrate differential effects of L-PGDS treatment on cell proliferation and apoptosis in VSMCs isolated from SHR versus WKY controls. L-PGDS (50 g/ml) was able to significantly inhibit VSMC proliferation and DNA synthesis and induce the apoptotic genes bax, bcl-x, and ei24 in SHR but had no effect on WKY cells. Hyperglycemic conditions also had opposite effects, in which increased glucose concentrations (20 mM) resulted in decreased L-PGDS expression in control cells but actually stimulated L-PGDS expression in SHR. Furthermore, we examined the effect of L-PGDS incubation on insulin-stimulated Akt, glycogen synthase kinase-3␤ (GSK-3␤), and ERK phosphorylation. Unexpectedly, we found that when WKY cells were pretreated with L-PGDS, insulin could actually induce apoptosis and failed to stimulate Akt/GSK-3␤ phosphorylation. Insulin-stimulated ERK phosphorylation was unaffected by L-PGDS pretreatment in both cell lines. We propose that L-PGDS is involved in the balance of VSMC proliferation and apoptosis and in the increased expression observed in the hypertensive state is an attempt to maintain a proper equilibrium between the two processes via the induction of apoptosis and inhibition of cell proliferation.

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Section: Figsupporting

confidence: 93%

mentioning

confidence: 53%

Section: Methodsmentioning

confidence: 99%

“…In addition, conformation of apoptosis was determined by TUNEL assay as described previously (19) using the ApopDetek Cell Death Assay Kit (Enzo, Farmingdale, NY).…”

Section: Methodsmentioning

confidence: 99%

Section: L-pgds Pretreatment Inhibits the Insulin-induced Phosphorylamentioning

confidence: 99%

See 3 more Smart Citations

Prostaglandin D2 Synthase Inhibits the Exaggerated Growth Phenotype of Spontaneously Hypertensive Rat Vascular Smooth Muscle Cells

Ragolia

Palaia

Paric

et al. 2003

Journal of Biological Chemistry

Self Cite

View full text Add to dashboard Cite

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Glucocorticoids Increase Repair Potential in a Novel in vitro Human Airway Epithelial Wounding Model

2006

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Airway epithelial damage is a cardinal feature of chronic asthma. Agents which enhance epithelial repair without triggering uncontrolled fibrosis of the mesenchyme would be predicted to be useful in the management of asthma. We have developed a repeat wound model using mucociliated human bronchial epithelial cell (HBEC) cultures to define the key pathways involved in airway epithelial repair, and to study the effects of potential therapeutic agents on epithelial repair in a chronic setting. We show that repair occurs primarily by cell migration to close a defect; this process requires activation of the EGF receptor (EGFR) and subsequent tyrosine kinase signalling. Migration is accompanied by up-regulation of CD44 in motile cells at the wound margins with proliferation of non-migrating cells adjacent to the wound area. In long-term studies beta2 adrenoceptor agonists and phosphodiesterase (PDE) inhibitors have no effect on repair potential, in contrast chronic treatment with the glucocorticoid dexamethasone extends the lifespan of repeatedly wounded differentiated cultures. We suggest part of the beneficial effects of glucocorticoids in asthma is related to this ability to prolong repair potential following repeated episodes of epithelial injury.

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L-PGDS (Betatrace Protein) Inhibits Astrocyte Proliferation and Mitochondrial ATP Production in Vitro

Xin

Huber

Meyer³

et al. 2009

J Mol Neurosci

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L-PGDS is the most abundant protein present in the cerebrospinal fluid (CSF). Although CSF was believed to be homogenous in content, a previous study has showed that a marked concentration gradient of L-PGDS exists between the spinal CSF and the CSF in the subarachnoid space of patients with optic nerve disease (papilledema and normal-tension glaucoma). Astrocytes play a critical role in maintaining the integrity of axon function in the central nervous system and specifically in the optic nerve, and we therefore investigated the biochemical effects of L-PGDS on the proliferation of astrocytes and on the production of adenosine triphosphate (ATP) by astrocyte mitochondria. We found an inhibitory effect of L-PGDS on both proliferation of astrocytes and production of astrocyte ATP. The concentrations that inhibited astrocyte proliferation and ATP production were in the range measured in patients with idiopathic intracranial hypertension and in patients with normal-tension glaucoma. As the CSF is in contact with axons and mitochondria of the optic nerve (Bristow et al. Archives of Ophthalmology, 120, 791-796, 2002), we postulate that a change in the concentration of CSF protein such as L-PGDS could exercise a harmful effect on these structures.

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Elevated L-PGDS activity contributes to PMA-induced apoptosis concomitant with downregulation of PI3-K

Cited by 34 publications

References 31 publications

Prostaglandin D2 Synthase Inhibits the Exaggerated Growth Phenotype of Spontaneously Hypertensive Rat Vascular Smooth Muscle Cells

Prostaglandin D2 Synthase Inhibits the Exaggerated Growth Phenotype of Spontaneously Hypertensive Rat Vascular Smooth Muscle Cells

Glucocorticoids Increase Repair Potential in a Novel in vitro Human Airway Epithelial Wounding Model

L-PGDS (Betatrace Protein) Inhibits Astrocyte Proliferation and Mitochondrial ATP Production in Vitro

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