Impairment of Na+,K+-ATPase in CD95(APO-1)-induced human T-cell leukemia cell apoptosis mediated by glutathione depletion and generation of hydrogen peroxide

Yin, Wei; Cheng, Wei; Shen, Weisen; Liu, Shu; Zhao, Jianping; Zhang, J; Zc, Hua

doi:10.1038/sj.leu.2404791

Cited by 32 publications

(25 citation statements)

References 37 publications

(36 reference statements)

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“…Because AVD and changes in ionic homeostasis (particularly K ϩ loss) also regulate the progression of apoptosis (5,35,39,42,51,52,60,61,63,72,73,(75)(76)(77), we explored the link between GSH depletion, changes in ionic homeostasis, and apoptosis. FasL induces the activation of ORCC; however, net Cl Ϫ depletion does not occur during FasL-induced apoptosis, and thus, changes in intracellular Cl Ϫ distribution do not participate in the progression of cell death (62).…”

Section: Discussionmentioning

confidence: 99%

“…In addition, apoptosis is not only paralleled by changes in K ϩ content but also by changes in intracellular Na ϩ and plasma membrane depolarization, and these changes are associated with impairment of the Na ϩ -K ϩ -ATPase (73, 76, 80 -82). Indeed, recent reports demonstrated that impairment in the Na ϩ -K ϩ -ATPase activity during apoptosis is also regulated by GSH depletion (76,83).…”

Section: Discussionmentioning

confidence: 99%

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Glutathione Depletion and Disruption of Intracellular Ionic Homeostasis Regulate Lymphoid Cell Apoptosis

Franco

DeHaven

Sifre

et al. 2008

Journal of Biological Chemistry

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Intracellular glutathione (GSH) depletion is an important hallmark of apoptosis. We have recently shown that GSH depletion by its extrusion regulates apoptosis independently of excessive reactive oxygen species accumulation. However, the mechanisms by which GSH depletion regulates apoptosis are still unclear. Because disruption of intracellular ionic homeostasis, associated with apoptotic volume decrease (AVD), is necessary for the progression of apoptotic cell death, we sought to evaluate the relationship between GSH transport and ionic homeostasis during Fas ligand (FasL)-induced apoptosis in Jurkat cells. GSH depletion in response to FasL was paralleled by distinct degrees of AVD identified by differences in cellular forward scatter and electronic impedance analysis. Inhibition of GSH efflux prevented AVD, K ؉ loss, and the activation of two distinct ionic conductances, mediated by Kv1.3 and outward rectifying Cl Apoptosis or programmed cell death is a ubiquitous energydependent, evolutionary conserved process. Under physiological conditions it is important not only in the constant turnover of cells in all tissues, but also during the normal development and senescence of the organism. Moreover, its deregulation has been observed to occur as either a cause or consequence of distinct pathologies (1, 2). A clear example is apoptosis mediated by Fas ligand (FasL) 2 receptor (Fas/CD95/Apo-1) activation, which is necessary for immune system homeostasis because of its role in the rapid clearance of immunoreactive T cells maintaining the immune balance and reducing the risk of autoimmune diseases (3). Apoptosis is a highly ordered process characterized by the progressive activation of precise pathways leading to specific biochemical and morphological alterations. Initial stages of apoptosis are characterized by activation of initiator caspases, changes in the cellular redox potential, intracellular ionic homeostasis, cell shrinkage or apoptotic volume decrease (AVD), loss of membrane lipid asymmetry, and chromatin condensation. Later stages associated with the execution phase of apoptosis are characterized by execution caspase and endonuclease activation, apoptotic body formation, and cell fragmentation (4, 5). Reduced glutathione (GSH) is the most abundant low molecular weight thiol in animal cells and is the major determinant in the redox potential of the cell. It is involved in many cellular processes, including antioxidant defense, drug detoxification, signaling, and proliferation (6 -10). Glutathione loss is an early hallmark in the progression of cell death in response to different apoptotic stimuli (11)(12)(13)(14)(15)(16)(17)(18)(19). Death receptor (including Fas)-induced GSH depletion has been clearly associated with the activation of a plasma membrane transport mechanism and not to its oxidation by reactive oxygen species (ROS) (20 -23). Several studies have shown a correlation between GSH efflux and the progression of apoptosis, and inhibition of GSH loss is able to rescue cells from cell death progress...

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Glutathione Depletion and Disruption of Intracellular Ionic Homeostasis Regulate Lymphoid Cell Apoptosis

Franco

DeHaven

Sifre

et al. 2008

Journal of Biological Chemistry

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“…Alterations in the intracellular ionic homeostasis of the cell have been clearly linked to the progression of apoptosis. 107 Recent reports show that during apoptosis, cell shrinkage or apoptotic volume decrease, associated with the impairment in the Na þ -K þ -ATPase activity, 108 and activation of K þ and Cl À conductances 109,110 are also regulated by alterations in GSH homeostasis. A wide variety of ion channels and transporters have been shown to be regulated by ROS.…”

Section: Figure 1 Apoptotic Signaling Pathways (See Text For Further mentioning

confidence: 99%

Apoptosis and glutathione: beyond an antioxidant

2009

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Apoptosis is a conserved homeostatic process critical for organ and tissue morphogenesis, development, and senescence. This form of programmed cell death also participates in the etiology of several human diseases including cancer, neurodegenerative, and autoimmune disorders. Although the signaling pathways leading to the progression of apoptosis have been extensively characterized, recent studies highlight the regulatory role of changes in the intracellular milieu (permissive apoptotic environment) in the efficient activation of the cell death machinery. In particular, glutathione (GSH) depletion is a common feature of apoptotic cell death triggered by a wide variety of stimuli including activation of death receptors, stress, environmental agents, and cytotoxic drugs. Although initial studies suggested that GSH depletion was only a byproduct of oxidative stress generated during cell death, recent discoveries suggest that GSH depletion and post-translational modifications of proteins through glutathionylation are critical regulators of apoptosis. Here, we reformulate these emerging paradigms into our current understanding of cell death mechanisms. Apoptosis or programmed cell death is a ubiquitous homeostatic process involved in numerous biological systems. Under physiological conditions it is critical not only in the turnover of cells in tissues but also during normal development and senescence. Moreover, its deregulation has been widely observed to occur as either a cause or consequence of distinct pathologies including cancer, autoimmune, and neurodegenerative diseases. Apoptosis is a highly organized program induced by a myriad of stimuli that are characterized by the progressive activation of precise pathways leading to specific biochemical and morphological alterations in individual cells without involving an inflammatory response. Early stages of apoptosis are characterized by initiator caspase activation, cell shrinkage, loss of plasma membrane lipid asymmetry, and chromatin condensation. The execution phase of apoptosis is characterized by activation of executioner caspases and endonucleases, apoptotic body formation, and cell fragmentation 1 (Figure 1). Interestingly, recent studies have shown that changes in the intracellular milieu of the cells, such as alterations in the redox environment, are important regulators of the progression to apoptosis. 2 These discoveries have lead to the concept of a permissive apoptotic environment necessary for the activation of the proper signaling pathways regulating apoptosis. Glutathione (GSH) depletion is an early hallmark in the progression of cell death in response to a variety of apoptotic stimuli in numerous cell types 3,4 (Figure 2), although the exact role of GSH depletion in apoptosis is still controversial. We review recent data that show new insights into the understanding of the causes and consequences that alterations in the redox environment of the cell have on apoptosis.The Role of GSH in the Regulation of Apoptosis GSH synthesis, depletion, and apopt...

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“…The immunoblot analysis was performed as previously described [26]. Briefly, A549 cells after treatments were harvested and lysed, and the cleared lysate was separated by SDS-PAGE.…”

Section: Western-blot Analysismentioning

confidence: 99%

Involvement of Na+, K+-ATPase and its inhibitors in HuR-mediated cytokine mRNA stabilization in lung epithelial cells

Chen

Cao

et al. 2010

Cell. Mol. Life Sci.

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Increasing evidence demonstrates that Na(+), K(+)-ATPase plays an important role in pulmonary inflammation, but the mechanism remains largely unknown. In this study, we used cardiotonic steroids as Na(+), K(+)-ATPase inhibitors to explore the possible involvement of Na(+), K(+)-ATPase in pulmonary epithelial inflammation. The results demonstrated that mice after ouabain inhalation developed cyclooxygenase-2-dependent acute lung inflammation. The in vitro experiments further confirmed that Na(+), K(+)-ATPase inhibitors significantly stimulated cyclooxygenase-2 expression in lung epithelial cells of human or murine origin, the process of which was participated by multiple cis-elements and trans-acting factors. Most importantly, we first described here that Na(+), K(+)-ATPase inhibitors could evoke a significant Hu antigen R nuclear export in lung epithelial cells, which stabilized cyclooxygenase-2 mRNA by binding with a proximal AU-rich element within its 3'-untranslated region. In conclusion, HuR-mediated mRNA stabilization opens new avenues in understanding the importance of Na(+), K(+)-ATPase, as well as its inhibitors in inflammation.

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Impairment of Na+,K+-ATPase in CD95(APO-1)-induced human T-cell leukemia cell apoptosis mediated by glutathione depletion and generation of hydrogen peroxide

Cited by 32 publications

References 37 publications

Glutathione Depletion and Disruption of Intracellular Ionic Homeostasis Regulate Lymphoid Cell Apoptosis

Glutathione Depletion and Disruption of Intracellular Ionic Homeostasis Regulate Lymphoid Cell Apoptosis

Apoptosis and glutathione: beyond an antioxidant

Involvement of Na+, K+-ATPase and its inhibitors in HuR-mediated cytokine mRNA stabilization in lung epithelial cells

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