Upregulation of K<sub>2P</sub>5.1 potassium channels in multiple sclerosis

Bittner, Stefan; Bobak, Nicole; Herrmann, Alexander M.; Göbel, Kerstin; Meuth, Patrick; Höhn, K.; Stenner, Max-Philipp; Budde, Thomas; Wiendl, Heinz; Meuth, Sven G.

doi:10.1002/ana.22010

Cited by 63 publications

(74 citation statements)

References 37 publications

(48 reference statements)

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“…Cell-cycle analysis, apoptosis assay and fluorescence-activated cell sorting analysis Cell-cycle analysis was performed as described previously (Bittner et al, 2010). The data obtained were subsequently analyzed and evaluated using ModFit (Verity, Topsham, ME, USA).…”

Section: Western Blot Analysismentioning

confidence: 99%

Methylation-mediated repression of microRNA-143 enhances MLL–AF4 oncogene expression

Dou

Zheng

et al. 2011

Oncogene

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Fusion proteins containing the amino terminus of mixed lineage leukemia (MLL) are common in acute lymphoblastic leukemia (ALL) due to translocations. The MLL-AF4 fusion protein is generated by the translocation t(4;11)(q21;q23), and t(4;11)-positive ALL patients (MLL-AF4 ALL), have a notoriously poorer prognosis compared with patients with other MLL-associated leukemias. The detailed role of this fusion protein in leukemogenesis is not well understood. MicroRNAs (miRNAs) targeting the AF4 3 0 untranslated regions may modulate MLL-AF4 fusion protein levels, raising the question of whether regulation of these miRNAs are involved in the progression of MLL-AF4 ALL. In this study, we show that miR-143 was identified as a regulator of MLL-AF4 expression in MLL-AF4 ALL samples. Restoration of miR-143 in MLL-AF4-positive RS4;11 and MV4-11 cells induced apoptosis, negatively contributing to leukemia cell growth by reducing MLL-AF4 fusion protein levels. Furthermore, miR-143 was epigenetically repressed by promoter hypermethylation in MLL-AF4-positive primary blasts and cell lines, but not in normal bone marrow cells and MLL-AF4-negative primary blasts, which was directly associated with expression of the MLL-AF4 oncogene. This is the first study to show that miR-143 functions as a tumor suppressor in MLL-AF4 B-cell ALL. These data reveal the therapeutic promise of upregulating miR-143 expression for MLL-AF4 B-cell ALL.

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Section: Western Blot Analysismentioning

confidence: 99%

Methylation-mediated repression of microRNA-143 enhances MLL–AF4 oncogene expression

Dou

Zheng

et al. 2011

Oncogene

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“…The great importance of ionic currents in regulating T cell effector functions is underlined by the fact that T cell activation leads to an upregulation of a number of different ion channel genes. After chronic stimulation, human cytotoxic CD8 + T cells showed a close to 10-fold upregulation of mRNA coding for a member of the two-pore domain K + channel (K 2P ) family [10].…”

Section: Ion Channels On T Lymphocytesmentioning

confidence: 99%

Ion channels in autoimmune neurodegeneration

et al. 2011

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a b s t r a c tMultiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system characterized by widespread inflammation, focal demyelination and a variable degree of axonal and neuronal loss. Ionic conductances regulate T cell activation as well as neuronal function and thus have been found to play a crucial role in MS pathogenesis. Since present therapeutical approaches are only partially effective so far, ion channel modulation as a future strategy was brought into focus. Here, we review the status quo concerning recent findings from ion channel research in MS and its animal model, experimental autoimmune encephalomyelitis.

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“…As a consequence, the inhibition of either Kv1.3 or KCa3.1 by the appropriate selective blockers can inhibit cell proliferation and function in a T-cell-subtype-specific manner, as discussed later in this review. In addition to Kv1.3, other K þ channels, for example two-pore domain containing K þ channels (K2Ps, such as TASK1-TASK3 [11,12]), have been suggested to contribute to membrane potential regulation of T cells.…”

Section: Physiological Functions Of Ion Channels In Immune Cellsmentioning

confidence: 99%

Ion channels and anti-cancer immunity

Panyi

Beeton

Felipe

2014

Phil. Trans. R. Soc. B

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The outcome of a malignant disease depends on the efficacy of the immune system to destroy cancer cells. Key steps in this process, for example the generation of a proper Ca 2þ signal induced by recognition of a specific antigen, are regulated by various ion channel including voltage-gated Kv1.3 and Ca 2þ -activated KCa3.1 K þ channels, and the interplay between Orai and STIM to produce the Ca 2þ -release-activated Ca 2þ (CRAC) current required for T-cell proliferation and function. Understanding the immune cell subset-specific expression of ion channels along with their particular function in a given cell type, and the role of cancer tissue-dependent factors in the regulation of operation of these ion channels are emerging questions to be addressed in the fight against cancer disease. Answering these questions might lead to a better understanding of the immunosuppression phenomenon in cancer tissue and the development of drugs aimed at skewing the distribution of immune cell types towards killing of the tumour cells.

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Upregulation of K_2P5.1 potassium channels in multiple sclerosis

Abstract: Selective targeting of K(2P)5.1 may hold therapeutic promise for MS and putatively other T-cell-mediated disorders.

Cited by 63 publications

References 37 publications

Methylation-mediated repression of microRNA-143 enhances MLL–AF4 oncogene expression

Methylation-mediated repression of microRNA-143 enhances MLL–AF4 oncogene expression

Ion channels in autoimmune neurodegeneration

Ion channels and anti-cancer immunity

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Upregulation of K2P5.1 potassium channels in multiple sclerosis

Abstract: Selective targeting of K(2P)5.1 may hold therapeutic promise for MS and putatively other T-cell-mediated disorders.

Cited by 63 publications

References 37 publications

Methylation-mediated repression of microRNA-143 enhances MLL–AF4 oncogene expression

Methylation-mediated repression of microRNA-143 enhances MLL–AF4 oncogene expression

Ion channels in autoimmune neurodegeneration

Ion channels and anti-cancer immunity

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Product

Resources

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Upregulation of K_2P5.1 potassium channels in multiple sclerosis