Academic Journal
Targeting TRPM2 Channels Impairs Radiation-Induced Cell Cycle Arrest and Fosters Cell Death of T Cell Leukemia Cells in a Bcl-2-Dependent Manner
| العنوان: | Targeting TRPM2 Channels Impairs Radiation-Induced Cell Cycle Arrest and Fosters Cell Death of T Cell Leukemia Cells in a Bcl-2-Dependent Manner |
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| المؤلفون: | Dominik Klumpp, Milan Misovic, Kalina Szteyn, Ekaterina Shumilina, Justine Rudner, Stephan M. Huber |
| المصدر: | Oxidative Medicine and Cellular Longevity, Vol 2016 (2016) |
| بيانات النشر: | Hindawi Limited |
| سنة النشر: | 2016 |
| المجموعة: | Directory of Open Access Journals: DOAJ Articles |
| مصطلحات موضوعية: | Cytology, QH573-671 |
| الوصف: | Messenger RNA data of lymphohematopoietic cancer lines suggest a correlation between expression of the cation channel TRPM2 and the antiapoptotic protein Bcl-2. The latter is overexpressed in various tumor entities and mediates therapy resistance. Here, we analyzed the crosstalk between Bcl-2 and TRPM2 channels in T cell leukemia cells during oxidative stress as conferred by ionizing radiation (IR). To this end, the effects of TRPM2 inhibition or knock-down on plasma membrane currents, Ca2+ signaling, mitochondrial superoxide anion formation, and cell cycle progression were compared between irradiated (0–10 Gy) Bcl-2-overexpressing and empty vector-transfected Jurkat cells. As a result, IR stimulated a TRPM2-mediated Ca2+-entry, which was higher in Bcl-2-overexpressing than in control cells and which contributed to IR-induced G2/M cell cycle arrest. TRPM2 inhibition induced a release from G2/M arrest resulting in cell death. Collectively, this data suggests a pivotal function of TRPM2 in the DNA damage response of T cell leukemia cells. Apoptosis-resistant Bcl-2-overexpressing cells even can afford higher TRPM2 activity without risking a hazardous Ca2+-overload-induced mitochondrial superoxide anion formation. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| تدمد: | 1942-0900 1942-0994 |
| Relation: | http://dx.doi.org/10.1155/2016/8026702; https://doaj.org/toc/1942-0900; https://doaj.org/toc/1942-0994; https://doaj.org/article/75de5747d86a4a2fbd63ae69772be66f |
| DOI: | 10.1155/2016/8026702 |
| الاتاحة: | https://doi.org/10.1155/2016/8026702 https://doaj.org/article/75de5747d86a4a2fbd63ae69772be66f |
| رقم الانضمام: | edsbas.676EF21D |
| قاعدة البيانات: | BASE |
Full Text Finder | تدمد: | 19420900 19420994 |
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| DOI: | 10.1155/2016/8026702 |