Ion homeostasis and apoptosis

Yu, Shan Ping; Canzoniero, Lorella M.T.; Choi, Dennis W.

doi:10.1016/s0955-0674(00)00228-3

Cited by 359 publications

(229 citation statements)

References 85 publications

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“…The latter could be a threshold value, required for cell survival, by preventing cells from losing K + ions, a prerequisite to enter the apoptotic pathway. 55,56 Alternatively, such values could be apt to maintain, in a properly activated state, [57][58][59] those voltage-dependent proteins involved in cell signalling, as well as to control the appropriate Ca 2+ entry into the cells through voltage-dependent channels. 60 On the whole, based on data reported in this study, we propose to include K + channel encoding genes, in particular the herg gene, among novel molecular markers of hematological disorders that are involved in the regulation of hemopoietic cell proliferation.…”

Section: Discussionmentioning

confidence: 99%

HERG potassium channels are constitutively expressed in primary human acute myeloid leukemias and regulate cell proliferation of normal and leukemic hemopoietic progenitors

et al. 2002

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An important target in the understanding of the pathogenesis of acute myeloid leukemias (AML) relies on deciphering the molecular features of normal and leukemic hemopoietic progenitors. In particular, the analysis of the mechanisms involved in the regulation of cell proliferation is decisive for the establishment of new targeted therapies. To gain further insight into this topic we report herein a novel approach by analyzing the role of HERG K + channels in the regulation of hemopoietic cell proliferation. These channels, encoded by the human ether-agò -gò -related gene (herg), belong to a family of K + channels, whose role in oncogenesis has been recently demonstrated. We report here that herg is switched off in normal peripheral blood mononuclear cells (PBMNC) as well as in circulating CD34 + cells, however, it is rapidly turned on in the latter upon induction of the mitotic cycle. Moreover, herg appears to be constitutively activated in leukemic cell lines as well as in the majority of circulating blasts from primary AML. Evidence is also provided that HERG channel activity regulates cell proliferation in stimulated CD34 + as well as in blast cells from AML patients. These results open new perspectives on the pathogenetic role of HERG K + channels in leukemias.

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Section: Discussionmentioning

confidence: 99%

HERG potassium channels are constitutively expressed in primary human acute myeloid leukemias and regulate cell proliferation of normal and leukemic hemopoietic progenitors

et al. 2002

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“…18 This hypothetical scheme has as yet to be tested experimentally. As pointed out above, although poorly studied, H þ carriers other than NHE (such as the Cl À /HCO 3 À exchanger, Na þ -dependent Cl À /HCO 3 À exchanger or Na þ -HCO 3 À cotransporter), as well as membrane ion channels, might also be involved in the Fas-dependent acidification; with regard to this latter point, inhibition of an outwardly rectifying chloride channel (ORCC) activated upon CD95 receptor ligation in T lymphocytes has thus been shown to abolish the apoptosis-related acidification. 7 Clearly, the role of such transporters deserves further investigation.…”

Section: Intracellular Acidification In Apoptosismentioning

confidence: 99%

“…11 At present, nothing is known about the role of such functions in apoptosis. One should also consider the role of the other ions carried by these transporters, especially Na þ and HCO 3 À ions, which have been reported to participate in apoptosis. 72,73 …”

Section: Intracellular Alkalinization In Apoptosismentioning

confidence: 99%

“…1,2 In contrast, little is understood about the accompanying changes in intracellular ionic homeostasis, although there exists a certain amount of work on apoptosis-associated variations in Ca 2 þ i , K þ i and H þ i . As the role of Ca 2 þ i and K þ i in apoptosis has been recently reviewed, 3 the present review will essentially focus on H þ i homeostasis and will discuss recent advances in this field.…”

Section: Introductionmentioning

confidence: 99%

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Alterations of intracellular pH homeostasis in apoptosis: origins and roles

2004

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Intracellular pH (pH i ) has an important role in the maintenance of normal cell function, and hence this parameter has to be tightly controlled within a narrow range, largely through the activity of transporters located at the plasma membrane. These transporters can be modulated by endogenous or exogenous molecules as well as, in some pathological situations, leading to pH i changes that have been implicated in both cell proliferation and cell death. Whereas intracellular alkalinization seems to be a common feature of proliferative processes, the precise role of pH i in apoptosis is still unclear. The present review gathers the most recent advances along with previous data on both the origin and the role of pH i alterations in apoptosis and highlights the major concerns that merit further research in the future. Special attention is given to the possible role played by pH i -regulating transporters.

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“…Intra and extra-cellular ions play an important role in a variety of cellular functions and the concentration of intra-cellular ions is tightly regulated in cells by numerous energy-requiring cellular mechanisms [1]. For example, extra-cellular signaling pathways regulate cellular function by means of calcium ions acting through effector enzymes [2].…”

Section: Introductionmentioning

confidence: 99%

An endogenous calcium-dependent, caspase-independent intranuclear degradation pathway in thymocyte nuclei: Antagonism by physiological concentrations of K+ ions

Ajiro

Bortner

Westmoreland

et al. 2008

Experimental Cell Research

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Calcium ions have been implicated in apoptosis for many years, however the precise role of this ion in the cell death process remains incomplete. We have extensively examined the role of Ca 2+ on nuclear degradation in vitro using highly purified nuclei isolated from non-apoptotic rat thymocytes. We show that these nuclei are devoid of CAD (caspase-activated DNase), and DNA degradation occurs independent of caspase activity. Serine proteases rather than caspase-3 appear necessary for this Ca 2+ -dependent DNA degradation in nuclei. We analyzed nuclei treated with various concentrations of Ca 2+ in the presence of both a physiological (140 mM) and apoptotic (40 mM) concentration of KCl. Our results show that a 5-fold increase in Ca 2+ is required to induce DNA degradation at the physiological KCl concentration compared to the lower, apoptotic concentration of the cation. Ca 2+ -induced internucleosomal DNA degradation was also accompanied by the release of histones, however the apoptotic-specific phosphorylation of histone H2B does not occur in these isolated nuclei. Interestingly, physiological concentrations of K + inhibit both Ca 2+ -dependent DNA degradation and histone release suggesting a reduction of intracellular K + is necessary for this apoptosis-associated nuclear degradation in cells. Together, these data define an inherent caspaseindependent catabolic pathway in thymocyte nuclei that is sensitive to physiological concentrations of interacellular cations.

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Ion homeostasis and apoptosis

Cited by 359 publications

References 85 publications

HERG potassium channels are constitutively expressed in primary human acute myeloid leukemias and regulate cell proliferation of normal and leukemic hemopoietic progenitors

HERG potassium channels are constitutively expressed in primary human acute myeloid leukemias and regulate cell proliferation of normal and leukemic hemopoietic progenitors

Alterations of intracellular pH homeostasis in apoptosis: origins and roles

An endogenous calcium-dependent, caspase-independent intranuclear degradation pathway in thymocyte nuclei: Antagonism by physiological concentrations of K+ ions

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