Role of prostaglandins and leukotrienes in volume regulation by Ehrlich ascites tumor cells

Lambert, Ian Henry; Hoffmann, Else K.; Christensen, Poul

doi:10.1007/bf01871187

Cited by 121 publications

(89 citation statements)

References 28 publications

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“…Our data and other reports as well (39,40) demonstrate that tumor cells produce PGE 2 , which is known to be cytocidal for immunocytes (41,42). Kolenko et al (21) also reported that PGE 2 can down-regulate the expression of ␥c expression and Jak-3 activity in T cells.…”

Section: Discussionsupporting

confidence: 84%

Curcumin Prevents Tumor-induced T Cell Apoptosis through Stat-5a-mediated Bcl-2 Induction

Bhattacharyya

Mandal

Saha

et al. 2007

Journal of Biological Chemistry

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Patients with advanced cancer exhibit multifaceted defects in their immune capacity, which are likely to contribute to an increased susceptibility to infections and disease progression. We demonstrated earlier that curcumin inhibits tumor growth and prevents immune cell death in tumor-bearing hosts. Here we report that tumor-induced immunodepletion involves apoptosis of thymic CD4 ؉ /CD8 ؉ single/double positive cells as well as loss of circulating CD4؉ /CD8 ؉ T cells. Administration of curcumin to tumor-bearing animals resulted in restoration of progenitor, effecter, and circulating T cells. In fact, tumor burden decreased the expression level of the pro-proliferative protein Bcl-2 while increasing the pro-apoptotic protein Bax in T cells. Curcumin down-regulated the Bax level while augmenting Bcl-2 expression in these cells, thereby protecting the immunocytes from tumor-induced apoptosis. A search for the upstream mechanism revealed down-regulation of the common cytokine receptor ␥ chain (␥c) expression in T cells by tumor-secreted prostaglandin E 2 . As a result, Jak-3 and Stat-5a phosphorylation and to a lesser extent Stat-5b phosphorylation were also decreased in T cells. These entire phenomena could be reverted back by curcumin, indicating that this phytochemical restored the cytokine-dependent Jak-3/Stat-5a signaling pathway in T cells of tumor bearers. Overexpressed Stat-5a/constitutively active Stat-5a1*6 but not Stat-5b could efficiently elevate Bcl-2 levels and protect T cells from tumor-induced death, whereas C-terminal truncated Stat-5a 713 overexpression failed to do so, indicating the importance of Stat-5a signaling in T cell survival. Thus, these results raise the possibility of inclusion of curcumin in successful therapeutic regimens against cancer.

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Section: Discussionsupporting

confidence: 84%

Curcumin Prevents Tumor-induced T Cell Apoptosis through Stat-5a-mediated Bcl-2 Induction

Bhattacharyya

Mandal

Saha

et al. 2007

Journal of Biological Chemistry

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“…12 The series of events between a hypotonic challenge and COX-2 activity in JG cells is likely to include cell swelling and PLA 2 activation as observed in several cell types. 9 Hypotonicity-induced stimulation of COX-2 activity in cultured cells has been observed previously. 16 Indomethacin inhibits not only COX activity but also prostaglandin transport.…”

Section: Discussionmentioning

confidence: 55%

“…8 A distinct role for phospholipase A2 (PLA 2 ) and prostaglandin E2(PGE 2 ) EP2 receptors in swelling-induced activation of regulatory processes in single cells has been demonstrated. 9 Prostaglandin E 2 and PGI 2 enhance outward current and renin secretion from JG cells. 10 In the study presented here, we hypothesized that JG cells respond to a decrease in extracellular osmolality by water uptake, Cyclooxygenase (COX)-dependent prostaglandin formation and renin release.…”

mentioning

confidence: 99%

Hypotonicity-Induced Renin Exocytosis from Juxtaglomerular Cells Requires Aquaporin-1 and Cyclooxygenase-2

Friis

Madsen²,

Svenningsen³

et al. 2009

Journal of the American Society of Nephrology

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The mechanism by which extracellular hypotonicity stimulates release of renin from juxtaglomerular (JG) cells is unknown. We hypothesized that osmotically induced renin release depends on water movement through aquaporin-1 (AQP1) water channels and subsequent prostanoid formation. We recorded membrane capacitance (C m ) by whole-cell patch clamp in single JG cells as an index of exocytosis. Hypotonicity increased C m significantly and enhanced outward current. Indomethacin, PLA 2 inhibition, and an antagonist of prostaglandin transport impaired the C m and current responses to hypotonicity. Hypotonicity also increased exocytosis as determined by a decrease in single JG cell quinacrine fluorescence in an indomethacin-sensitive manner. In single JG cells from COX-2 Ϫ/ Ϫ and AQP1 Ϫ/ Ϫ mice, hypotonicity increased neither C m nor outward current, but 0.1-M PGE 2 increased both in these cells. A reduction in osmolality enhanced cAMP accumulation in JG cells but not in renin-producing As4.1 cells; only the former had detectable AQP1 expression. Inhibition of protein kinase A blocked the hypotonicity-induced C m and current response in JG cells. Taken together, our results show that a 5 to 7% decrease in extracellular tonicity leads to AQP1-mediated water influx in JG cells, PLA 2 /COX-2-mediated prostaglandin-dependent formation of cAMP, and activation of PKA, which promotes exocytosis of renin. Juxtaglomerular (JG) granular cells in the terminal part of the renal afferent glomerular arterioles are the only cells in the organism that synthesize preprorenin, process it to active renin, and store active renin in mature secretory granules. The rate of renin granule exocytosis determines the level of activation of the renin-angiotensin-aldosterone system. Renin secretion from most 1,2 but not all 3,4 in vitro preparations displays a uniquely high sensitivity to changes in extracellular osmolality such that a moderate reduction in the extracellular osmolality leads to rapid increases in renin secretion. The sensing and transduction events for renin release in response to osmotic perturbations are not known. At the glomerular tuft, the extracellular osmolality may vary depending on sodium chloride (NaCl)transport rate by the adjacent macula densa and thick ascending limb cells, which are relatively water impermeable. 5,6 JG cell capacitance (C m ), an index of cell surface area, increased when extracellular osmolality was decreased by 5 to 10% at the single cell level. 7 This observation shows exocytotic release of renin in response to decreases in extracellular osmolality. 7 Introduction of a pipette solution

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“…As shown in Figure 3 NDGA added to the extracellular fluid is able to block the swelling-activated chloride current within seconds. It is, therefore, very unlikely that inhibition of lipoxygenase by NDGA (Lambert et al, 1987) or gossypol (Hamasaki & Tai, 1985) is responsible for the observed effect, since the time needed to induce leukotriene production after reduction of extracellular osmolarity in Ehrlich cells is 5 to 10 min (Lambert et al, 1987). Furthermore, NDGA as well as gossypol impede the cyclic AMP-dependent chloride currents (at albeit higher concentrations, see below) which is independent of the leukotriene metabolism.…”

Section: Discussionmentioning

confidence: 98%

Blockade of swelling‐induced chloride channels by phenol derivatives

Gschwentner

Jungwirth

Hofer

et al. 1996

British J Pharmacology

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1 In NIH3T3 fibroblasts, the chloride channel involved in regulatory volume decrease (RVD) was identified as ACln, a protein isolated from a cDNA library derived from Madin Darby canine kidney (MDCK) cells. ICI5 expressed in Xenopus laevis oocytes gives rise to an outwardly rectifying chloride current, sensitive to the extracellular addition of nucleotides and the known chloride channel blockers, DIDS (4,4'-diisothiocyanatostilbene-2,2'-disulphonic acid) and NPPB (5-nitro-2-(3-phenylpropylamino)-benzoic acid). We set out to study whether substances structurally similar to NPPB are able to interfere with RVD. 2 RVD in NIH3T3 fibroblasts and MDCK cells is temperature-dependent. 3 RVD, the swelling-dependent chloride current and the depolarization seen after reducing extracellular osmolarity can be blocked by gossypol and NDGA (nordihydroguaiaretic acid), both structurally related to NPPB. 4 The cyclic AMP-dependent chloride current elicited in CaCo cells is less sensitive to the two substances tested while the calcium-activated chloride current in fibroblasts is insensitive. 5The binding site for the two phenol derivatives onto ICan seems to be distinct but closely related to the nucleotide binding site identified as G x G x G, a glycine repeat located at the predicted outer mouth of the Icn channel protein.

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Role of prostaglandins and leukotrienes in volume regulation by Ehrlich ascites tumor cells

Cited by 121 publications

References 28 publications

Curcumin Prevents Tumor-induced T Cell Apoptosis through Stat-5a-mediated Bcl-2 Induction

Curcumin Prevents Tumor-induced T Cell Apoptosis through Stat-5a-mediated Bcl-2 Induction

Hypotonicity-Induced Renin Exocytosis from Juxtaglomerular Cells Requires Aquaporin-1 and Cyclooxygenase-2

Blockade of swelling‐induced chloride channels by phenol derivatives

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