Stimulation of thromboxane release from primary cell cultures derived from human astrocytic glioma biopsies

Murphy, Seán; Welk, Greg; Thwin, Soe Soe

doi:10.1002/glia.440030307

Cited by 15 publications

(10 citation statements)

References 26 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…TXAS, by virtue of catalysing the formation of TXA 2 , has previously been shown to have mitogenic and proliferative effects (Murphy et al, 1990;Pradono et al, 2002;Yoshizato et al, 2002;Kim et al, 2003;Nie et al, 2004;Moussa et al, 2005;Watkins et al, 2005;Sakai et al, 2006). Thus, simply decreasing its synthesis may have some antiproliferative effects in cancer cells, which could result in an additive or synergistic effect on chemotherapeutic agents.…”

Section: Discussionmentioning

confidence: 99%

Inhibition of thromboxane synthase activity modulates bladder cancer cell responses to chemotherapeutic agents

et al. 2007

View full text Add to dashboard Cite

Recently, we reported prognostic significance of thromboxane synthase (TXAS) gene expression in invasive bladder cancer. The positive correlation between elevated TXAS expression and shorter patient survival supports a potential role for TXAS-regulated pathways in tumor metastases. In this study, using immunohistochemical analysis, we found an increased expression of TXAS protein in bladder cancer. Treatment of T24 and transitional cell carcinoma TCC-SUP bladder cancer cells with the TXAS inhibitors furegrelate or ozagrel induced an apoptotic effect measured as an increase in caspase-3 activation and cell death, and decreased survivin expression. Pharmacological inhibition of TXAS using the TXAS inhibitor furegrelate increased sensitivity to the chemotherapeutic agents cisplatin and paclitaxel. Molecular inhibition of TXAS expression by siRNA significantly decreased cell growth and migration. In concordance with the pharmacological data, siRNAmediated reduction of TXAS expression increased sensitivity to cisplatin and paclitaxel in T24 and TCC-SUP cells. In summary, the data support a role for the thromboxane A 2 pathway in the pathogenesis of bladder cancer and the potential utility of modulation of this signaling pathway for cancer chemotherapy.

show abstract

Section: Discussionmentioning

confidence: 99%

Inhibition of thromboxane synthase activity modulates bladder cancer cell responses to chemotherapeutic agents

et al. 2007

View full text Add to dashboard Cite

show abstract

“…In this respect, oligodendrocytes may have access to TXA 2 in at least three possible manners. First, although the identification of an exact in vivo source remains controversial, TXA 2 has been shown to be generated by astrocytes (38), microglia (39), and vascular endothelial cells (10) in culture. With regard to astrocytes, a ubiquitously distributed glial cell, activation of phospholipase A 2 and production of TXA 2 by thromboxane synthase occurs in response to stimulation of cells by mediators such as platelet-activating factor (40) and ATP (41).…”

Section: Discussionmentioning

confidence: 99%

The Identification and Characterization of Oligodendrocyte Thromboxane A2 Receptors

Blackman¹,

Dawson²,

Antonakis³

et al. 1998

Journal of Biological Chemistry

View full text Add to dashboard Cite

The presence of functional thromboxane A 2 receptors in neonatal rat oligodendrocytes and human oligodendroglioma cells was investigated using immunocytochemistry, ligand affinity chromatography, radioligand binding analysis, immunoblot analysis, and calcium mobilization studies. Immunocytochemical studies revealed the presence of receptor protein on both oligodendrocytes and human oligodendroglioma cells. Ligand affinity chromatography allowed for the purification of a protein with an electrophoretic mobility (55 kDa) indistinguishable from human platelet thromboxane A 2 receptors. This affinity purified protein was immunoreactive against a polyclonal anti-thromboxane A 2 receptor antibody. Intact human oligodendroglioma cells specifically bound Thromboxane A 2 (TXA 2 ) 1 is a bioactive arachidonic acid metabolite with thrombotic, vasospastic, and bronchospastic properties (1-3). It has been implicated in a variety of physiological and pathophysiological states (4). The receptor for TXA 2 has been purified (5, 6), cloned, and sequenced, and the structure of the gene indicates that this receptor is a member of the seven transmembrane domain, G-protein-coupled receptor superfamily. The receptor protein has been located in a variety of tissues including blood platelets (7), vascular smooth muscle (8, 9), vascular endothelium (10), placenta (11), and kidney (12) and appears to be directly involved in the regulation of intracellular calcium levels (13). In this regard, previous studies have provided evidence that the TXA 2 receptor protein is coupled to at least one G-protein, i.e. G q in platelets (14, 15) and astrocytes (16), and appears to modulate phospholipase C-␤ activity resulting in activation of the inositol triphosphate second messenger system (17, 18).Although highly specific agonists and antagonists have proven to be of significant value in characterizing TXA 2 receptors in a number of different cell lines, little information is currently available concerning their existence or function in the central nervous system. To a large extent, this has been due to the presence of high lipid concentrations in central nervous system tissue. Thus, nonspecific binding has obscured the demonstration of receptor binding in solubilized brain, due to the lipophilic nature of TXA 2 receptor ligands. In addition, the heterogeneity of cell types in the central nervous system has complicated attempts at receptor localization at a cellular level.Based on these limitations, previous studies have employed cultured cell systems in an effort to investigate the presence of TXA 2 receptors in the central nervous system. In these experiments, it was demonstrated that cultured rabbit astrocytes were capable of specifically binding the TXA 2 ligand ONO . These results, therefore, provided evidence that at least one cellular component of the central nervous system possesses TXA 2 receptor activity. However, since astrocytes are ubiquitously distributed in the brain, it has not been possible to ascribe a specific or unique function for...

show abstract

“…10 Cultures showed a small amount of reactivity for fibronectin (CRTG1 5%, STTG1 6%, and WITG2 2%), using rabbit anti-human fibronectin (Cappel 1:5,000); however, GFAP and fibronectin have been reported to colocalize in human astrocytes in culture. 21 Astrocytes were grown at 37°C in a humidified atmosphere of 95% air and 5% CO 2 and were used between passage 5 and 30.…”

Section: Cell Culturementioning

confidence: 99%

Human astrocytes contain two distinct angiotensin receptor subtypes.

et al. 1991

View full text Add to dashboard Cite

The ability of angiotensin peptides to stimulate prostaglandin release and raise intracellular calcium levels by activating a phosphoinositide-specific phospholipase C was assessed in three human astrocytoma cell lines (CRTG3, STTG1, and VVITG2). The addition of angiotensin II to CRTG3 cells resulted in a dose-dependent release of prostaglandin E, and prostacyclin, the production of inositol 1,4,5-trisphosphate, and the mobilization of intracellular calcium. Angiotensin-(l-7), previously considered to be an inactive metabolite of angiotensin II, was as potent as angiotensin II for prostaglandin release but did not activate phospholipase C or mobilize intracellular calcium. In contrast, angiotensin-(2-8) caused only a slight increase in prostaglandin release, even though it was as effective as angiotensin II in augmenting inositol 1,4,5-trisphosphate production and calcium mobilization. Moreover, neither the release of prostaglandins in response to angiotensin II or angiotensin-(l-7) nor the mobilization of intracellular calcium in response to angiotensin II required extracellular calcium. Angiotensin II and angiotensin-(l-7) caused the release of prostaglandins from all three human astrocytoma cell lines, but changes in the level of intracellular calcium in response to angiotensin II only occurred in CRTG3 cells. Although previous studies have provided evidence for angiotensin receptor subtypes on the basis of selectivity of antagonists or signal transduction mechanisms, these data suggest that human astrocytes contain multiple angiotensin receptor subtypes on the basis of their response to different angiotensin heptapeptides -angiotensin-(1-7) and angiotensin-(2-8). Furthermore, the data also suggest that preferential production of angiotensin-(1-7) and angiotensin-(2-8) may be one level of regulation whereby a particular signal transduction pathway [i.e., calcium mobilization by angiotensin-(2-8) or prostaglandin release by angiotensin-(l-7)] is selectively activated. {Hypertension 1991;18:32-39)

show abstract

Stimulation of thromboxane release from primary cell cultures derived from human astrocytic glioma biopsies

Cited by 15 publications

References 26 publications

Inhibition of thromboxane synthase activity modulates bladder cancer cell responses to chemotherapeutic agents

Inhibition of thromboxane synthase activity modulates bladder cancer cell responses to chemotherapeutic agents

The Identification and Characterization of Oligodendrocyte Thromboxane A2 Receptors

Human astrocytes contain two distinct angiotensin receptor subtypes.

Contact Info

Product

Resources

About