Dynamics of nuclear localization sites for COX-2 in vascular endothelial cells

Parfenova, Helena; Parfenov, V. N.; Shlopov, Boris V.; Levine, Vladimir; Falkos, Sheryl; Pourcyrous, Massroor; Leffler, Charles W.

doi:10.1152/ajpcell.2001.281.1.c166

Cited by 75 publications

(70 citation statements)

References 46 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The sparse, nonuniform COX-2 immunostaining that seemed to be absent from much of the endothelium and limited to the nuclear or perinuclear regions of the endothelial cells differed markedly from the dense uniform COX-1 immunostaining of the endothelium. A predominantly nuclear or perinuclear pattern of COX-2 immunostaining has been reported previously in vascular endothelial cells (Morita et al, 1995;Parfenova et al, 2001). Parfenova et al (2001) proposed that nuclear/perinuclear localization of COX-2 in unstimulated endothelium may influence its function because they observed increased product formation with increased expression of COX-2 in the cytoplasm of cytokine-treated endothelial cells.…”

Section: Discussionmentioning

confidence: 61%

“…A predominantly nuclear or perinuclear pattern of COX-2 immunostaining has been reported previously in vascular endothelial cells (Morita et al, 1995;Parfenova et al, 2001). Parfenova et al (2001) proposed that nuclear/perinuclear localization of COX-2 in unstimulated endothelium may influence its function because they observed increased product formation with increased expression of COX-2 in the cytoplasm of cytokine-treated endothelial cells. In the present study, the sparse, nuclear or perinuclear localization of COX-2 may limit its activity such that the COX-2 identified may be insufficient to support 5,6-EET-induced contraction.…”

Section: Discussionmentioning

confidence: 61%

See 1 more Smart Citation

Cyclooxygenase (COX)-1 and COX-2 Participate in 5,6-Epoxyeicosatrienoic Acid-Induced Contraction of Rabbit Intralobar Pulmonary Arteries

Moreland¹,

Procknow²,

Sprague³

et al. 2007

J Pharmacol Exp Ther

View full text Add to dashboard Cite

Epoxyeicosatrienoic acids (EETs) have been reported to contract intralobar pulmonary arteries (PA) of the rabbit in a cyclooxygenase (COX)-dependent manner. In the present study, we observed that COX-1 and COX-2 isoforms were expressed in freshly isolated PA of healthy rabbits. We examined the hypothesis that both COX isoforms participate in 5,6-EET-induced contraction of rabbit intralobar PA. Selective inhibition of COX-1 with 300 nM 5-(4-chlorophenyl)-1-(4-methoxyphenyl)-3-(trifluoromethyl)-1H-pyrazole (SC-560) prevented 5,6-EET (1 ϫ 10 Ϫ8 -1 ϫ 10 Ϫ5 M)-induced contractions of isolated intralobar rabbit PA rings in a manner similar to that observed with the nonselective cyclooxygenase inhibitor indomethacin at 10 M. Selective inhibition of COX-2 with either 100 nM 5-bromo-2-(4-fluorophenyl)-3-(4-methylsulfonyl) thiophene (DUP-697) or 3 M N-(2-cyclohexyloxy-4-nitrophenyl) methanesulfonamide (NS-398) shifted the EC 50 value of 5,6-EET-induced PA contraction to the right but with considerably lower efficacy than SC-560. In rabbit PA, 5,6-EET-induced contraction was primarily dependent on COX-1 activity. Differential metabolism of 5,6-EET by COX-1 and COX-2 does not explain the primary dependence of PA contraction on COX-1 activity because 5,6-EET was metabolized similarly by both COX isoforms. COX-1 and -2 were expressed primarily in PA endothelium where COX-1 expression was dense and uniform, whereas COX-2 expression was sparse and nonuniform. 5,6-EET-induced PA contraction was endothelium-dependent. These results suggest that 5,6-EET-induced contraction is primarily dependent on COX-1 activity.

show abstract

Section: Discussionmentioning

confidence: 61%

Section: Discussionmentioning

confidence: 61%

Cyclooxygenase (COX)-1 and COX-2 Participate in 5,6-Epoxyeicosatrienoic Acid-Induced Contraction of Rabbit Intralobar Pulmonary Arteries

Moreland¹,

Procknow²,

Sprague³

et al. 2007

J Pharmacol Exp Ther

View full text Add to dashboard Cite

show abstract

“…Active-transcription factors are localized in nuclear matrix, where signal-transduction mechanism(s) are working [36]. The blockade of enhanced TGF-1-typeI receptor prevented COX-2 and HIF-1α expression in nuclei, consistent with an enhancement of TGF-1/TGF-1-typeI receptor couple, condition necessary for the autoregulatory-loop triggering [41].…”

mentioning

confidence: 76%

Nuclear co-localization and functional interaction of COX-2 and HIF-1α characterize bone metastasis of human breast carcinoma

Maroni

Matteucci²,

Luzzati³

et al. 2010

Breast Cancer Res Treat

View full text Add to dashboard Cite

The aim of the present paper was to identify nuclear co-localization of COX-2 and HIF-1α in human-bone metastasis of breast cancer, index of transcriptionally-activated cells and functional for gene expression. In particular, we verified whether hypoxia exerted a direct role on metastasis-gene expression or through COX-2 signaling, due to the relevance for clinical implications to individuate molecular targets for diagnosis and therapy. The experiments were performed in vitro with two autoregulatory loops triggered a specific array of transcription factors responsible for COX-2 transactivation. The novelty was that HGF and TGF-β1 biological signals were produced by hypoxic metastatic cells and, therefore, the microenvironment seemed to be modified by metastaticcell engraftment in the bone. In agreement, HIF-1α expression in bone-marrow supportive cells occurred in metastasis-bearing animals. Altogether, the data supported the pre-metastatic-niche theory. Our observations might be useful to design therapies against bone metastasis, by affecting the phenotype changes of metastatic cells occurring at the secondary growth site through COX-2-HIF-1 interaction.Keywords bone microenvironment · bone metastasis · breast cancer · COX-2 · HIF-1 3

show abstract

“…However, in vivo and in vitro studies in piglets demonstrated that COX-2 also functions in the cerebral vasculature of newborn pigs under basal nonstimulated conditions, thus potentially contributing to cerebral hemodynamics (7)(8)(9)(10)(11). COX-1 and COX-2 proteins were also detected by Western immunoblotting and immunostaining in endothelial cells from neonatal human brain at early passages (10).…”

mentioning

confidence: 99%

COX-1 and COX-2 Contributions to Basal and IL-1β-Stimulated Prostanoid Synthesis in Human Neonatal Cerebral Microvascular Endothelial Cells

et al. 2002

Self Cite

View full text Add to dashboard Cite

Mechanisms of endothelium-dependent regulation of cerebral circulation in human neonates are poorly understood owing to the lack of experimental data. Prostanoids, the products of the cyclooxygenase (COX) pathway, appear to be important regulators of blood flow in neonates. COX activity in cultured endothelial cells from small (60 -300 m) and large (Ͼ300 m) microvessels from the autopsy specimens of neonatal human cerebral cortex and cerebellum (22-26 wk gestational age) was detected as production of vasodilator prostanoids, prostacyclin [as 6-keto-prostaglandin (PG) F 1␣ ] and PGE 2 from arachidonic acid. Treatment of neonatal human cerebral microvascular endothelial cells (hCMVEC) with IL-1␤ (50 ng/mL, 17 h) stimulated COX activity 5-to 20-fold. Basal and IL-1␤-stimulated COX activities were inhibited by NS-398, indicating substantial COX-2 contribution to endothelial prostanoid synthesis in neonatal human brain cortex and cerebellum at rest and when mimicking the inflammatory conditions. Increased COX-2-linked activity in response to IL-1␤ was observed in hCMVEC from both cerebrum and cerebellum (5-to 20-fold), while under the same conditions elevated COX-1-linked activity was detected only in hCMVEC from cerebellum (5-to 10-fold). In IL-1␤-treated hCMVEC, a shift toward PGE 2 as the major vasodilator product of the COX pathway was observed. Acute treatment with the protein tyrosine kinase inhibitor, tyrphostin 25, inhibited basal and IL-1␤-induced COX activities, suggesting the importance of posttranslational modifications in endothelial COX-2 activation in human brain. Altogether, these data indicate that both COX-1 and COX-2 contribute to endothelial prostanoid synthesis in the neonatal human brain under basal conditions and in response to proinflammatory cytokine IL-1␤. Cerebral circulatory disorders produce serious complications in human neonates, such as cerebral hemorrhages and hypoxicischemic injuries, that can result in life-long neurologic dysfunction in survivors including cerebral palsy, epilepsy, and mental retardation. Mechanisms of the regulation of cerebral circulation in neonates are understood incompletely, and experimental data are very limited. Vascular endothelium-derived dilator prostanoids, NO, and carbon monoxide are vasorelaxant factors essential in the regulation of cerebral blood flow. There are speciesspecific and age-dependent differences in physiologically relevant endothelial vasorelaxants in the cerebral circulation (1). In human newborns, prostanoids appear to be major factors that contribute to regulation of cerebral blood flow in response to hypercapnia, asphyxia, ischemia, and cerebral hemorrhage (1-3), and indomethacin is widely used in neonatal practice (2,4,5). Similarly, in newborn pigs, prostanoids contribute to the regulation of cerebral blood flow under basal conditions and in response to physiologically important stimuli, such as CO 2 , oxygen, and changes in blood pressure (1). Prostanoids are also important in the pathogenesis of inflammation because they alter in...

show abstract

Dynamics of nuclear localization sites for COX-2 in vascular endothelial cells

Cited by 75 publications

References 46 publications

Cyclooxygenase (COX)-1 and COX-2 Participate in 5,6-Epoxyeicosatrienoic Acid-Induced Contraction of Rabbit Intralobar Pulmonary Arteries

Cyclooxygenase (COX)-1 and COX-2 Participate in 5,6-Epoxyeicosatrienoic Acid-Induced Contraction of Rabbit Intralobar Pulmonary Arteries

Nuclear co-localization and functional interaction of COX-2 and HIF-1α characterize bone metastasis of human breast carcinoma

COX-1 and COX-2 Contributions to Basal and IL-1β-Stimulated Prostanoid Synthesis in Human Neonatal Cerebral Microvascular Endothelial Cells

Contact Info

Product

Resources

About