Phorbol ester‐induced cell death in PC‐12 cells overexpressing Bcl‐2 is dependent on the time at which cells are treated

Hahn, Michael; Mayne, George C.

doi:10.1016/j.cellbi.2004.02.003

Cited by 4 publications

(3 citation statements)

References 55 publications

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“…It can therefore be said that sensitivity of Raji cells to apoptotic cell‐death induction by iron deprivation reflects the particular metabolic status of the cells, concerning iron utilization, and its change does not involve cell genetic change and subsequent selection of the adapted clone(s). Similar findings, showing that the sensitivity of cells to the tested death stimulus reflects the status of the cells, have been presented by several other authors recently (Hahn & Mayne 2004; Yao et al . 2005).…”

Section: Discussionsupporting

confidence: 91%

Sensitivity of cells to apoptosis induced by iron deprivation can be reversibly changed by iron availability

Koc¹,

Nadova²,

Kovář³

2006

Cell Proliferation

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We tested the effect of iron deprivation on cell death induction in human Raji cells pre-adapted to differing availability of extracellular iron. Iron deprivation was achieved by incubation in a defined iron-free medium. Original Raji cells have previously been adapted to long-term culture in a defined medium with 5 microg/ml of iron-saturated human transferrin as a source of iron. Raji/lowFe cells were derived from original Raji cells by subsequent adaptation to culture in the medium with 50 microm ferric citrate as a source of iron. Raji/lowFe-re cells were derived from Raji/lowFe cells by re-adaptation to the transferrin-containing (5 microg/ml) medium. Iron deprivation induced cell death in both Raji cells and Raji/lowFe-re cells; that is, cells pre-adapted to a near optimum source of extracellular iron (5 microg/ml of transferrin). However, Raji/lowFe cells preadapted to a limited source of extracellular iron (50 microm ferric citrate) became resistant to the induction of cell death by iron deprivation. We demonstrated that cell death induction by iron deprivation in Raji cells correlates with the activation of executioner caspase-3 and the cleavage of caspase-3 substrate, poly-ADP ribose polymerase. Two other executioner caspases, caspase-7 and caspase-6, were not activated. Taken together, we suggest that in human Raji cells, iron deprivation induces apoptotic cell death related to caspase-3 activation. However, the sensitivity of the cells to death induction by iron deprivation can be reversibly changed by extracellular iron availability. The cells pre-adapted to a limited source of extracellular iron became resistant.

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Section: Discussionsupporting

confidence: 91%

Sensitivity of cells to apoptosis induced by iron deprivation can be reversibly changed by iron availability

Koc¹,

Nadova²,

Kovář³

2006

Cell Proliferation

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“…Depending on the cells studied, EBV lytic cycle can be intentionally induced by various stimuli, including anti-immunoglobulin cross-linking, chemical agents like sodium butyrate and TPA, Ca 2+ ionophores, or TGF-β. It is also known that some chemical inducers like sodium butyrate and TPA can induce cell death [ 29 ]. Therefore, we utilized another BL cell line, MUTU-1 (Lat.…”

Section: Resultsmentioning

confidence: 99%

Interferon-γ-inducible protein 16 (IFI16) is required for the maintenance of Epstein-Barr virus latency

Gina

Roy

Ansari

et al. 2017

Virol J

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BackgroundEpstein-Barr virus (EBV) exhibits both lytic and latent (Lat. I, II, and III) phases in an infected individual. It’s during the latent phase of EBV that all EBV-associated cancers, including Burkitt’s lymphoma, nasopharyngeal carcinoma and lymphoproliferative disease arise. Interferon-γ-inducible protein 16 (IFI16) is a well-established innate immune sensor and viral transcriptional regulator involved in response to invading DNA viruses. During latency, IFI16 remains in the nucleus, in part bound to the EBV genome; however, neither its role in EBV lytic cycle or latency has been established.MethodsShort interfering RNA against IFI16 and IFI16 overexpression were used to identify the role of IFI16 in the maintenance of EBV latency I. We also studied how induction of the lytic cycle affected IFI16 using the EBV positive, latently infected Akata or MUTU-1 cell lines. Akata cells were induced with TPA and MUTU-1 cells with TGF-β up to 96 h and changes in IFI16 protein were analyzed by Western blotting and immunofluorescence microscopy. To assess the mechanism of IFI16 decrease, EBV DNA replication and late lytic transcripts were blocked using the viral DNA polymerase inhibitor phosphonoacetic acid.ResultsKnockdown of IFI16 mRNA by siRNA resulted in enhanced levels of EBV lytic gene expression from all temporal gene classes, as well as an increase in the total EBV genome abundance, whereas overexpression of exogenous IFI16 reversed these effects. Furthermore, 96 h after induction of the lytic cycle with either TPA (Akata) or TGF-β (MUTU-1), IFI16 protein levels decreased up to 80% as compared to the EBV-negative cell line BJAB. Reduction in IFI16 was observed in cells expressing EBV lytic envelope glycoprotein. The decreased levels of IFI16 protein do not appear to be dependent on late lytic transcripts of EBV but suggest involvement of the immediate early, early, or a combination of both gene classes.ConclusionsReduction of IFI16 protein levels following lytic cycle induction, as well as reactivation from latency after IFI16 mRNA knockdown suggests that IFI16 is crucial for the maintenance of EBV latency. More importantly, these results identify IFI16 as a unique host factor protein involved in the EBV lifecycle, making it a potential therapeutic target to combat EBV-related malignancies.

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“…Phorbol 12-myristate 13-acetate (PMA) is a known agonist of protein kinase C [25] and a potent inducer of NGF gene expression and secretion [21] . However, phorbol esters such as PMA also affect proliferative and cell survival pathways within the cell and have long been recognized as powerful tumor promoters [ 26 , 27 , 28 ] and apoptosis inducers [ 29 , 30 , 31 , 32 , 33 , 34 ], depending upon the phorbol ester concentration and the state of the cell and its microenvironment. Hence, the clinical use of PMA (and other phorbol ester analogs) as an inducer of NGF is undesirable.…”

Section: Introductionmentioning

confidence: 99%

Induction of nerve growth factor by phorbol 12-myristate 13-acetate is dependent upon the mitogen activated protein kinase pathway

Davis

Calvert

Roberts

et al. 2018

Heliyon

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Several small molecules have been identified that induce glial cells to synthesize and secrete nerve growth factor (NGF), a critical neurotrophin that supports neuronal growth and survival, and as such show promise in the development of drugs for the chemoprevention of Alzheimer's disease. To map the signal transduction cascade leading to NGF synthesis and secretion, cultured human glial cells were stimulated by phorbol 12-myristate 13-acetate (PMA), an agonist of Protein Kinase C. Changes in intracellular protein phosphorylation states were evaluated by reverse phase protein microarrays (RPPA), selectively screening over 130 protein endpoints. Of these, 55 proteins showed statistically significant changes in phosphorylation state due to cellular exposure to PMA. A critical signal transduction pathway was identified, and subsequent validation by ELISA and qPCR revealed that the signaling proteins Raf, MEK, ERK, and the signal transduction factor CREB are all essential to the upregulation of NGF gene expression by PMA. Additionally, members of the RSK family of kinases appear to be involved in glial secretion (exocytosis) of the NGF protein. Furthermore, through RPPA, the effects of PMA on apoptosis signaling events and cell proliferation were differentiated from the pathway to NGF upregulation. Overall, this study reveals potential protein targets for the rational design of Alzheimer's therapeutics.

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Phorbol ester‐induced cell death in PC‐12 cells overexpressing Bcl‐2 is dependent on the time at which cells are treated

Cited by 4 publications

References 55 publications

Sensitivity of cells to apoptosis induced by iron deprivation can be reversibly changed by iron availability

Sensitivity of cells to apoptosis induced by iron deprivation can be reversibly changed by iron availability

Interferon-γ-inducible protein 16 (IFI16) is required for the maintenance of Epstein-Barr virus latency

Induction of nerve growth factor by phorbol 12-myristate 13-acetate is dependent upon the mitogen activated protein kinase pathway

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