The Roles of Calcium and Cyclic Amp in Cell Proliferation

Whitfield, J. F.; Boynton, Alton L.; MacManus, J. P.; Rixon, R. H.; Sikorska, Marianna; Tsang, Benjamin K.; Walker, P. Roy; Swierenga, S.H.H.

doi:10.1111/j.1749-6632.1980.tb15980.x

Cited by 197 publications

(65 citation statements)

References 53 publications

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“…The importance of Ca*' in cell proliferation has already been recognized many years ago [34,35]. For instance, oncogenic growth factors such as epidermal or platelet-derived growth factor cause an increase of the cytosolic Ca*' level by stimulating Ca*+ influx into the cell or by release of Ca*' from the endoplasmic reticulum through turnover of phosphatidyl inositols.…”

Section: Apoptosis Oncogenesis Pro-oxidantsmentioning

confidence: 99%

Pro‐oxidants and mitochondrial Ca²⁺: their relationship to apoptosis and oncogenesis

1993

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Apoptosis is a physiological process for active cell removal. One of its hallmarks is an increased cytosolic Ca2+ content. Several genes involved in apoptosis control have been identified, but their mode of action is not understood in detail. Apoptosis may relate to oncogenesis, in that some malignant tumors may grow because genes engaged in apoptosis control are altered. L929 cells overexpressing the proto‐oncogen bcl‐2 have an increased mitochondrial membrane potential (δψ), as have many carcinoma cells, bcl‐2 protects L929 cells against apoptosis caused by pro‐oxidant‐induced mitochondrial Ca2+ ‘cycling’ and increased cytosolic Ca2+ levels. Nerve growth factor, which induces catalase, and inhibitors of mitochondrial Ca2+ release also prevent apoptosis. It is suggested that a pro‐oxidant‐induced Ca2+ release from mitochondria, followed by Ca2+ cycling and ATP depletion, is a common basic event during apoptosis. Accordingly, maintenance of δψ stabilizes mitochondria, thereby prevents apoptosis, and may confer increased growth potential to cells.

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Section: Apoptosis Oncogenesis Pro-oxidantsmentioning

confidence: 99%

Pro‐oxidants and mitochondrial Ca²⁺: their relationship to apoptosis and oncogenesis

1993

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“…The current, which decayed exponentially after reaching a peak, was first activated at about -50 mV and attained its maximum peak amplitude at about -20 mV in a 10 mM Ca2+ solution. Outward current was negligible for the potential range more negative than +30 (5)(6)(7)(8)(9). Because lymphocytes are small (=10 ,um in diameter), it has been impossible to examine electrical properties of their membranes faithfully by using conventional intracellular microelectrode techniques.…”

mentioning

confidence: 99%

“…First, external Ca2+ is required at the stage of target cell cytolysis by effector lymphocytes, when the lethal hit is thought to take place (1)(2)(3). Second, Ca24 is necessary for lymphocyte proliferation when lymphocytes are stimulated by antigens (4) and mitogens (5)(6)(7)(8)(9). Because lymphocytes are small (=10 ,um in diameter), it has been impossible to examine electrical properties of their membranes faithfully by using conventional intracellular microelectrode techniques.…”

mentioning

confidence: 99%

Voltage-gated Ca2+ channel in mouse myeloma cells.

Fukushima¹,

Hagiwara²

1983

Proc. Natl. Acad. Sci. U.S.A.

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Electrical properties of the cell membrane were studied in the neoplastic lymphocyte, mouse myeloma cell line S194, by using the whole-cell patch clamp technique. Inward Ca2+ currents due to voltage-gated Ca2+ channels were found. The current, which decayed exponentially after reaching a peak, was first activated at about -50 mV and attained its maximum peak amplitude at about -20 mV in a 10 mM Ca2+ solution. Outward current was negligible for the potential range more negative than +30 (5)(6)(7)(8)(9). Because lymphocytes are small (=10 ,um in diameter), it has been impossible to examine electrical properties of their membranes faithfully by using conventional intracellular microelectrode techniques. Recent introduction of the "gigohm seal" patch clamp technique by Sigworth and Neher (10) enabled us to study membrane properties of those small cells successfully (11,12). We selected mouse neoplastic lymphocytes, myeloma cell line S194, because they were easily kept under tissue culture condition and because they were slightly larger than normal lymphocytes. We found inward currents carried by-the voltage-gated Ca24 channel that displayed voltage-dependent inactivation. MATERIALS AND METHODSMouse myeloma cell line, S194/5.XXO, was cultured in suspension in RPMI 1640 medium with glutamine (Flow Laboratories), containing 10% calf serum. This cell line synthesizes IgA but does not secrete antibodies into the medium (13). The mean diameter of the myeloma cells was 13 am. The gigohm seal patch clamp technique introduced by Sigworth and Neher (10) was used to study membrane properties. The details of the whole-cell voltage clamp with the patch electrode were similar to those described previously (11). The normal external solution contained 138 mM NaCl, 5 mM KCl, 10 mM CaCl2, 1 mM MgCl2, 17 mM glucose, and 10 mM Hepes (pH 7.4). Other solutions were made by replacing the CaCl2 or NaCl (or both) of the normal solution isosmotically. The patch electrode was filled with a solution containing 150 mM KCI, 1 mM MgCl2, 5 mM EGTA, 2.5 mM CaC12 (pCa * 7), and 10 mM Hepes (pH = 7.4) and had a resistance of 5-15 M11. The external solution was continuously perfused after the myeloma cells had settled on the bottom of the dish. Experiments were performed at 24-260C. Output of the current-voltage converter was filtered at 1 kHz, digitized at sampling intervals of 400 jisec, and stored in a computer. The zero-current membrane potential in the normal solution was -20 to -30 mV. It was likely, however, that the resting potential was actually more negative; this was due to relatively small ratios between the seal (2-15 GQ) and wholecell input (0.5-2 Gfl) resistances. In most experiments, voltage clamp was performed by holding the membrane potential in the vicinity of--90 mV. Errors caused-by liquid junction potentials were corrected as described (11). RESULTS Inward Current Carried by Ca2". Transient inward currents were observed when the membrane potential was made positive from the holding potential of -94 mV (Fig. LA). When 10...

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“…Previous studies have demonstrated a direct calcium involvement in the initiation of DNA synthesis in many cell types (Whitfield et al, 1980). It is therefore possible that Cd blockage of cells in the Sphase of the cell cycle observed in this study, may be mediated by direct effect on calcium mediated cell functions.…”

Section: Resultsmentioning

confidence: 53%

Cell cycle analysis of interleuklin-6 Stimulated B9 hybridoma cell line in the Presence of cadmium

Orupabo¹

2005

Journal of Applied Sciences and Environmental Management

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Interleukin-6 is a multifunctional Cytokine. In-vitro, interleukin-6 (IL-6) stimulated murine hybridoma B9 cell proliferation is well established. Cadmium inhibition of this response to IL-6 has been previously reported. Cell cycle analysis of IL-6 stimulated B9 cells in the presence or absence of cadmium (Cd) was performed in this study to examine the mechanism of Cd inhibition of B9 cell line proliferation. DNA stained cells were analyzed using electronically programmable flow cytometer. The results show a requirement for IL-6 signals in Go/G1 phase activation and transition out of S-phase of the cell cycle. Cd induced blockage of cells in the S-phase of the cell cycle was observed when IL-6 stimulated cells were treated with 10µM CdC1 2 . Increasing the concentration of IL-6 from 3 to 100 pg/ml reversed the Cd-blockage of cells in the S-phase of the cell cycle. The ability of IL-6 (at high concentration) to reverse Cd-induced blockage of cells in the S-phase of the cell cycle, suggests that IL-6 signal (s) required for transition of cells out of S-phase is a potential target for Cd. @JASEM

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The Roles of Calcium and Cyclic Amp in Cell Proliferation

Cited by 197 publications

References 53 publications

Pro‐oxidants and mitochondrial Ca²⁺: their relationship to apoptosis and oncogenesis

Pro‐oxidants and mitochondrial Ca²⁺: their relationship to apoptosis and oncogenesis

Voltage-gated Ca2+ channel in mouse myeloma cells.

Cell cycle analysis of interleuklin-6 Stimulated B9 hybridoma cell line in the Presence of cadmium

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The Roles of Calcium and Cyclic Amp in Cell Proliferation

Cited by 197 publications

References 53 publications

Pro‐oxidants and mitochondrial Ca2+: their relationship to apoptosis and oncogenesis

Pro‐oxidants and mitochondrial Ca2+: their relationship to apoptosis and oncogenesis

Voltage-gated Ca2+ channel in mouse myeloma cells.

Cell cycle analysis of interleuklin-6 Stimulated B9 hybridoma cell line in the Presence of cadmium

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Pro‐oxidants and mitochondrial Ca²⁺: their relationship to apoptosis and oncogenesis

Pro‐oxidants and mitochondrial Ca²⁺: their relationship to apoptosis and oncogenesis