Regulatory volume decrease is actively modulated during the cell cycle

Wang, Liwei; Chen, Lixin; Zhu, Linyan; Rawle, Michelle; Nie, Sihuai; Zhang, Jin; Zhong, Ping; Cai, Kedi; Jacob, T. J. C.

doi:10.1002/jcp.10156

Cited by 44 publications

(37 citation statements)

References 31 publications

(54 reference statements)

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“…This effect was partly linked to the inhibition of voltage-dependent potassium channels (25,26). In the present work, we have examined in leukemic and SCLC 3 cells a putative interaction between sigma-1 receptors and volume-regulated chloride currents (VRCC) that have been involved in the control of the cell cycle (27)(28)(29). We demonstrate for the first time that the sigma-1 receptor modulates VRCC and cell volume regulation properties leading to alterations of cell proliferation and apoptosis mechanisms.…”

mentioning

confidence: 84%

“…For example, the inhibition of these currents by blockers such as NPPB stops cell proliferation in liver cells (43). Moreover, the expression of chloride channels is tightly regulated along the cell cycle progression in carcinoma cells (27). Thus, we first studied the effects of highly specific sigma-1 receptor ligands on VRCC.…”

Section: Table 1 Kinetic Properties Of the Vrcc Activation In Hek Andmentioning

confidence: 99%

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Cancer Cell Cycle Modulated by a Functional Coupling between Sigma-1 Receptors and Cl– Channels

Renaudo¹,

L’Hoste²,

Guizouarn

et al. 2007

Journal of Biological Chemistry

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The sigma-1 receptor is an intracellular protein characterized as a tumor biomarker whose function remains mysterious. We demonstrate herein for the first time that highly selective sigma ligands inhibit volume-regulated chloride channels (VRCC) in small cell lung cancer and T-leukemia cells. Sigma ligands and VRCC blockers provoked a cell cycle arrest underlined by p27 accumulation. In stably sigma-1 receptor-transfected HEK cells, the proliferation rate was significantly lowered by sigma ligands when compared with control cells. Sigma ligands produced a strong inhibition of VRCC in HEK-transfected cells but not in control HEK. Surprisingly, the activation rate of VRCC was dramatically delayed in HEK-transfected cells in the absence of ligands, indicating that sigma-1 receptors per se modulate cell regulating volume processes in physiological conditions. Volume measurements in hypotonic conditions revealed indeed that the regulatory volume decrease was delayed in HEK-transfected cells and virtually abolished in the presence of igmesine in both HEK-tranfected and T-leukemic cells. Moreover, HEKtransfected cells showed a significant resistance to staurosporine-induced apoptosis volume decrease, indicating that sigma-1 receptors protect cancer cells from apoptosis. Altogether, our results show for the first time that sigma-1 receptors modulate "cell destiny" through VRCC and cell volume regulation.Sigma receptors are intracellular proteins that were first postulated as opioid receptors on the basis of pharmacological and behavioral studies (1). Finally, 20 years of pharmacological studies and the cloning of the sigma-1 receptor subtype in 1996 revealed indeed that the "sigma-binding site" corresponded to a 24-kDa protein unrelated to other mammalian proteins and localized in the inner face of the plasma membrane and the membranes of the endoplasmic reticulum and the nucleus (2-5). Although high concentrations of neurosteroids have been shown to interact with brain sigma-1 receptors in behavioral studies (for review see Ref. 6), no high affinity endogene sigma ligand has been identified yet. Nonetheless, exogene compounds from disparate chemical classes ((ϩ)-benzomorphans, cocaine, guanidines, and neuroleptics for example) have been characterized or developed as highly selective sigma ligands (7). The sigma-1 receptors are expressed in various tissues including the brain, the pituitary, and the liver (2, 8 -10). Surprisingly, very high levels of sigma receptors have been detected in tumor cells when compared with normal cells (11,12). Indeed, the expression of sigma receptors in cancer biopsies is correlated with the proliferating state of the cells so that these proteins are now commonly considered to be tumor biomarkers (13,14). Consequently, many sigma ligands are developed nowadays for imagery (positon emission tomography scan) to detect early stage tumors (15, 16). However, if sigma receptors represent exciting targets to detect cancers in vivo, very few data are available on both the function and the action m...

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mentioning

confidence: 84%

Section: Table 1 Kinetic Properties Of the Vrcc Activation In Hek Andmentioning

confidence: 99%

Cancer Cell Cycle Modulated by a Functional Coupling between Sigma-1 Receptors and Cl– Channels

Renaudo¹,

L’Hoste²,

Guizouarn

et al. 2007

Journal of Biological Chemistry

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“…Cell volume and RVD rate were measured using the methods described by us previously [13,14]. Cell suspension of control cells was obtained by trypsinizing cultured cells in a flask and resuspending them in culture medium.…”

Section: Measurements Of Cell Volume and Rvdmentioning

confidence: 99%

Involvement of regulatory volume decrease in the migration of nasopharyngeal carcinoma cells

et al. 2005

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The transwell chamber migration assay and CCD digital camera imaging techniques were used to investigate the relationship between regulatory volume decrease (RVD) and cell migration in nasopharyngeal carcinoma cells (CNE-2Z cells). Both migrated and non-migrated CNE-2Z cells, when swollen by 47% hypotonic solution, exhibited RVD which was inhibited by extracellular application of chloride channel blockers adenosine 5'-triphosphate (ATP), 5-nitro-2-(3-phenylpropylamino) benzoic acid (NPPB) and tamoxifen. However, RVD rate in migrated CNE-2Z cells was bigger than that of non-migrated cells and the sensitivity of migrated cells to NPPB and tamoxifen was higher than that of nonmigrated cells. ATP, NPPB and tamoxifen also inhibited migration of CNE-2Z cells. The inhibition of migration was positively correlated to the blockage of RVD, with a correlation coefficient (r) = 0.99, suggesting a functional relationship between RVD and cell migration. We conclude that RVD is involved in cell migration and RVD may play an important role in migratory process in CNE-2Z cells.

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“…For instance, variations in RVD capacity were reported during different phases of the cycle, with cells in G 1 having the highest RVD capacity. 41 Progressive diminution is evident, because it was difficult to activate their RVD mechanisms in cells that had progressed through the S-phase. This differential RVD capacity during cell cycle advancement could be the result of changes in the volume set point or in the activation level of ion efflux mechanisms, both of which events allow cells to reach the threshold size required for progression through cell cycle restriction points.…”

Section: Discussionmentioning

confidence: 99%

Potassium-Chloride Cotransporter Mediates Cell Cycle Progression and Proliferation of Human Corneal Epithelial Cells

Capó-Aponte

Wang²,

Akıncı³

et al. 2007

Cell Cycle

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Epidermal growth factor (EGF)-induced proliferation of corneal epithelial cells contributes to its renewal, which maintains the protective and refractive properties of the cornea. This study characterized in human corneal epithelial cells (HCEC) the role of the potassium-chloride cotransporter (KCC) in mediating (1) EGF-induced mitogen-activated protein kinase (MAPK) pathway activation; (2) increases in cell cycle progression; and (3) proliferation. The KCC inhibitor [(dihydroindenyl)oxy] alkanoic acid (DIOA) and KCC activator N-ethylmaleimide (NEM), suppressed and enhanced EGF-induced p44/42MAPK activation, respectively. Such selective modulation was mirrored by corresponding changes in cell proliferation and shifts in cell cycle distribution. DIOA induced a 20% increase in G 0 /G 1 -phase cell population, whereas NEM induced a 22% increase in the proportion of cells in the G 2 /M-phase and accelerated the transition from G 0 /G 1 -phase to the S-phase. Associated with these changes, KCC1 content in a plasma membrane enriched fraction increased by 300%. Alterations in regulatory volume capacity were associated with corresponding changes in both KCC1 membrane content and activity. These results indicate that EGF-induced increases in KCC1 activity and content modulate cell volume changes required for (1) activation of the p44/42MAPK signaling pathway, (2) cell cycle progression, and (3) increases in cell proliferation.

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Regulatory volume decrease is actively modulated during the cell cycle

Cited by 44 publications

References 31 publications

Cancer Cell Cycle Modulated by a Functional Coupling between Sigma-1 Receptors and Cl– Channels

Cancer Cell Cycle Modulated by a Functional Coupling between Sigma-1 Receptors and Cl– Channels

Involvement of regulatory volume decrease in the migration of nasopharyngeal carcinoma cells

Potassium-Chloride Cotransporter Mediates Cell Cycle Progression and Proliferation of Human Corneal Epithelial Cells

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