Flow cytometric study of changes in the intracellular free calcium during the cell cycle

Pande, Gopal; Kumar, Nirbhay; Manogaran, Pulicat

doi:10.1002/(sici)1097-0320(19960501)24:1<55::aid-cyto7>3.0.co;2-h

Cited by 40 publications

(17 citation statements)

References 26 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It controls G1 progression, G1/S and G2/M transition phases by regulating expression of several calcium-dependent signaling pathways, such as calmodulin, CaM-Kinase, and calcineurin [3], [4], [5]. Therefore, identification of the pathways involved in Ca 2+ influx regulating the cell proliferation are in the focus of a number of investigations.…”

Section: Introductionmentioning

confidence: 99%

Orai3 Constitutes a Native Store-Operated Calcium Entry That Regulates Non Small Cell Lung Adenocarcinoma Cell Proliferation

Ay¹,

Benzerdjerb

Sevestre

et al. 2013

PLoS ONE

View full text Add to dashboard Cite

Orai channels have been associated with cell proliferation, survival and metastasis in several cancers. The present study investigates the expression and the role of Orai3 in cell proliferation in non-small cell lung cancer (NSCLC). We show that Orai3 is over-expressed in cancer tissues as compared to the non-tumoral ones. Furthermore, Orai3 staining is stronger in high grade tumors. Pharmacological inhibition or knockdown of Orai3 significantly reduced store operated calcium entry (SOCE), inhibited cell proliferation and arrested cells of two NSCLC cell lines in G0/G1 phase. These effects were concomitant with a down-regulation of cyclin D1, cyclin E, CDK4 and CDK2 expression. Moreover, Orai3 silencing decreased Akt phosphorylation levels. In conclusion, Orai3 constitutes a native SOCE pathway in NSCLC that controls cell proliferation and cell cycle progression likely via Akt pathway.

show abstract

Section: Introductionmentioning

confidence: 99%

Orai3 Constitutes a Native Store-Operated Calcium Entry That Regulates Non Small Cell Lung Adenocarcinoma Cell Proliferation

Ay¹,

Benzerdjerb

Sevestre

et al. 2013

PLoS ONE

View full text Add to dashboard Cite

show abstract

“…3). The expression of immediate-early genes in G 1 , such as FOS , JUN and MYC , and the retinoblastoma (RB1) phosphorylation at the G 1 /S boundary are regulated by Ca 2+ (Pande et al 1996; Takuwa et al 1996). Similarly, the Ca 2+ binding protein calmodulin (CaM) plays crucial roles in cell cycle progression through G 1 and mitosis (Kahl and Means 2003; Rasmussen and Means 1989).…”

Section: Calcium Waves In Signalingmentioning

confidence: 99%

Calcium wave signaling in cancer cells

Parkash

Asotra²

2010

Life Sciences

136

106

View full text Add to dashboard Cite

Ca2+ functions as an important signaling messenger right from beginning of the life to final moment of the end of the life. Ca2+ is needed at several steps of the cell cycle such as early G1, at the G1/S, and G2/M transitions. The Ca2+ signals in the form of time-dependent changes in intracellular Ca2+ concentrations, [Ca2+]i, are presented as brief spikes organized into regenerative Ca2+ waves. Ca2+-mediated signaling pathways have also been shown to play important roles in carcinogenesis such as transformation of normal cells to cancerous cells, tumor formation and growth, invasion, angiogenesis and metastasis. Since the global Ca2+ oscillations arise from Ca2+ waves initiated locally, it results in stochastic oscillations because although each cell has many IP3Rs and Ca2+ ions, the law of large numbers does not apply to the initiating event which is restricted to very few IP3Rs due to steep Ca2+ concentration gradients. The specific Ca2+ signaling information is likely to be encoded in a calcium code as the amplitude, duration, frequency, waveform or timing of Ca2+ oscillations and decoded again at a later stage. Since Ca2+ channels or pumps involved in regulating Ca2+ signaling pathways show altered expression in cancer, one can target these Ca2+ channels and pumps as therapeutic options to decrease proliferation of cancer cells and to promote their apoptosis. These studies can provide novel insights into alterations in Ca2+ wave patterns in carcinogenesis and lead to development of newer technologies based on Ca2+ waves for the diagnosis and therapy of cancer.

show abstract

“…12 Also, the levels of calcium (Ca 2ϩ ) culminate at the G1/S border. 13 It has been shown that the NO-forming reactions of hydroxyurea with hemoglobin or other blood constituents are too slow to account for NO production measured in vivo. 14 Several mechanisms of NO production from hydroxyurea have been proposed: one of them suggested a catalase-mediated pathway as a potential source, 15 another showed urease-dependent effects, 14 and the third one showed that horseradish peroxidase catalyzed NO formation from hydroxyurea.…”

Section: Introductionmentioning

confidence: 99%

Hydroxyurea induces the eNOS-cGMP pathway in endothelial cells

Čokić¹,

Beleslin-Čokić²,

Tomić³

et al. 2006

Blood

View full text Add to dashboard Cite

Hydroxyurea is a cell-cycle-specific drug that has been used to treat myeloproliferative diseases and sickle cell anemia. We have recently shown that hydroxyurea, like nitric oxide (NO)-donor compounds, increased cGMP levels in human erythroid cells. We show now that hydroxyurea increases endothelial-cell production of NO; this induction of NO in human umbilical vein endothelial cells (HUVECs) and human bone marrow endothelial cell line (TrHBMEC) is blocked by competitive inhibitors of NO synthase (NOS), such as N G -nitro-L-arginine-methyl ester (L-NAME) and N G -nitro-L-arginine. It is dependent on cAMP-dependent protein kinase (PKA) and protein kinase B (PKB/Akt) activity. We found that hydroxyurea dose-and time-dependently induced rapid and transient phosphorylation of eNOS at Ser1177 in a PKA-dependent manner; inhibitors of PKB/Akt could partially abrogate this effect. In addition, hydroxyurea induced cAMP and cGMP levels in a dose-dependent manner, as well as levels of intracellular calcium in HUVECs. These studies established an additional mechanism by which rapid and sustained effects of hydroxyurea may affect cellular NO levels and perhaps enhance the effect of NO in myeloproliferative diseases. IntroductionHydroxyurea is a cytostatic agent (S-phase inhibitor) that has been used to treat erythrocytosis and thrombocytosis in polycythemia vera and other myeloproliferative diseases. 1 More recently, hydroxyurea demonstrated therapeutic benefit for sickle cell anemia by increasing fetal hemoglobin (HbF). 2 In addition to the known inhibition of ribonucleotide reductase, hydroxyurea can be oxidized by heme groups to produce nitric oxide (NO) in vivo (in rats) and in humans. 3,4 Hydroxyurea reacts with oxyHb and deoxyHb to form metHb, which then reacts with another hydroxyurea to form iron nitrosyl hemoglobin (HbNO). 5 The formation of HbNO involves the specific transfer of NO from the -NHOH group of hydroxyurea by a series of intermediate reactions. 3 Additionally, in vivo production of NO may result from the hydrolysis of hydroxyurea to hydroxylamine, followed by the rapid reactions of hydroxylamine with Hb. 6 It has been reported that hydroxyurea administration significantly increased NO x (NO metabolites nitrite and nitrate) and cGMP levels in plasma of sickle cell patients. 7 We have recently shown that hydroxyurea, like NO-donor compounds, increased cGMP levels contributing to gamma-globin gene expression in human erythroid cells. 8 Hydroxyurea is completely absorbed and elimination is through both renal and nonrenal mechanisms. 9 The metabolism of hydroxyurea to NO most likely occurs in the liver. 3 Chemical oxidation of hydroxyurea with a variety of oxidants, including copper(II) ions, produces NO. 9,10 Hydroxyurea-treated vascular endothelial cells showed significant morphologic changes such as an increase in apparent cell size, accompanied by an increase in cell Na and K contents. 11 During hydroxyurea treatment, cells accumulate in the late G1 to early S phase of the cell cycle. 12 Also, the level...

show abstract

Flow cytometric study of changes in the intracellular free calcium during the cell cycle

Cited by 40 publications

References 26 publications

Orai3 Constitutes a Native Store-Operated Calcium Entry That Regulates Non Small Cell Lung Adenocarcinoma Cell Proliferation

Orai3 Constitutes a Native Store-Operated Calcium Entry That Regulates Non Small Cell Lung Adenocarcinoma Cell Proliferation

Calcium wave signaling in cancer cells

Hydroxyurea induces the eNOS-cGMP pathway in endothelial cells

Contact Info

Product

Resources

About