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Targeting TRPM2 Channels Impairs Radiation-Induced Cell Cycle Arrest and Fosters Cell Death of T Cell Leukemia Cells in a Bcl-2-Dependent Manner
Joint Authors
Klumpp, Dominik
Misovic, Milan
Szteyn, Kalina
Shumilina, Ekaterina
Rudner, Justine
Huber, Stephan M.
Source
Oxidative Medicine and Cellular Longevity
Issue
Vol. 2016, Issue 2016 (31 Dec. 2016), pp.1-14, 14 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2015-12-29
Country of Publication
Egypt
No. of Pages
14
Main Subjects
Abstract EN
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.
American Psychological Association (APA)
Klumpp, Dominik& Misovic, Milan& Szteyn, Kalina& Shumilina, Ekaterina& Rudner, Justine& Huber, Stephan M.. 2015. Targeting TRPM2 Channels Impairs Radiation-Induced Cell Cycle Arrest and Fosters Cell Death of T Cell Leukemia Cells in a Bcl-2-Dependent Manner. Oxidative Medicine and Cellular Longevity،Vol. 2016, no. 2016, pp.1-14.
https://search.emarefa.net/detail/BIM-1114280
Modern Language Association (MLA)
Klumpp, Dominik…[et al.]. Targeting TRPM2 Channels Impairs Radiation-Induced Cell Cycle Arrest and Fosters Cell Death of T Cell Leukemia Cells in a Bcl-2-Dependent Manner. Oxidative Medicine and Cellular Longevity No. 2016 (2016), pp.1-14.
https://search.emarefa.net/detail/BIM-1114280
American Medical Association (AMA)
Klumpp, Dominik& Misovic, Milan& Szteyn, Kalina& Shumilina, Ekaterina& Rudner, Justine& Huber, Stephan M.. Targeting TRPM2 Channels Impairs Radiation-Induced Cell Cycle Arrest and Fosters Cell Death of T Cell Leukemia Cells in a Bcl-2-Dependent Manner. Oxidative Medicine and Cellular Longevity. 2015. Vol. 2016, no. 2016, pp.1-14.
https://search.emarefa.net/detail/BIM-1114280
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-1114280