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
Dominik KlumppS M Huber

Abstract

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, Ca(2+) 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 Ca(2+)-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 Ca(2+)-overload-induced mitochondrial superoxide anion formation.

References

Apr 1, 1991·The Journal of Membrane Biology·P H Barry, J W Lynch
Oct 1, 1990·Molecular and Cellular Biology·J Cheng, M Haas
Sep 11, 2002·Apoptosis : an International Journal on Programmed Cell Death·J RudnerC Belka
Feb 7, 2003·The Journal of Membrane Biology·K InamuraK Furuichi
Feb 21, 2003·The Journal of Biological Chemistry·Wenyi ZhangBarbara A Miller
May 27, 2003·Cell Calcium·Inka HeinerAndreas Lückhoff
Oct 14, 2003·Biochemical Pharmacology·Scott A OakesLuca Scorrano
Dec 5, 2003·Nature·David E Clapham
Nov 19, 2004·Naunyn-Schmiedeberg's Archives of Pharmacology·K HillA D Randall
Nov 25, 2004·The Journal of Biological Chemistry·Anne-Laure PerraudAndrew M Scharenberg
Jun 14, 2005·Pflügers Archiv : European journal of physiology·Frank J P KühnAndreas Lückhoff
Nov 25, 2005·American Journal of Physiology. Cell Physiology·Wenyi ZhangBarbara A Miller
Apr 11, 2006·British Journal of Pharmacology·Robert KraftChristian Harteneck
May 27, 2006·Cell Death and Differentiation·P Pinton, R Rizzuto
Jan 16, 2007·Handbook of Experimental Pharmacology·J Eisfeld, A Lückhoff
Jan 24, 2007·Physiological Reviews·Bernd NiliusJohn A Peters
Apr 14, 2007·Cell Death and Differentiation·M GiacomelloT Pozzan
Oct 30, 2008·Cell Research·Ugo OrfanelliGiovanni Lavorgna
Nov 11, 2010·Cellular Physiology and Biochemistry : International Journal of Experimental Cellular Physiology, Biochemistry, and Pharmacology·Nicole HeiseGuido Henke
Dec 3, 2010·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Rebecca A KirklandJames L Franklin
Jun 28, 2011·Radiotherapy and Oncology : Journal of the European Society for Therapeutic Radiology and Oncology·Marc SteinleStephan M Huber
Feb 7, 2012·Biochimica Et Biophysica Acta·Katrine R LaubThomas Heimburg
Apr 21, 2012·Radiotherapy and Oncology : Journal of the European Society for Therapeutic Radiology and Oncology·Stephan M HuberKlaus Dittmann
Jun 19, 2012·Pflügers Archiv : European journal of physiology·Paola PizzoTullio Pozzan
Sep 8, 2012·Cellular and Molecular Life Sciences : CMLS·Giovanni MonacoGeert Bultynck
Jan 30, 2013·Cell Calcium·Stephan M Huber
Feb 28, 2013·Pflügers Archiv : European journal of physiology·Daniela PalmeStephan M Huber
Apr 4, 2013·Science Signaling·Jianjiong GaoNikolaus Schultz
Apr 23, 2013·Radiotherapy and Oncology : Journal of the European Society for Therapeutic Radiology and Oncology·Klaus DittmannStephan M Huber
Apr 27, 2013·The FEBS Journal·Christian DölleMathias Ziegler
Aug 24, 2013·Frontiers in Physiology·Stephan M HuberFranziska Eckert
Jun 5, 2015·Molecular Cancer Research : MCR·Benjamin StegenStephan M Huber

❮ Previous
Next ❯

Citations

May 12, 2016·European Biophysics Journal : EBJ·Benjamin StegenStephan M Huber
Sep 13, 2016·International Journal of Molecular Sciences·Lukas KlumppStephan M Huber
Jan 31, 2017·Experimental Biology and Medicine·Jin QinYang Liu
Jul 19, 2018·American Journal of Physiology. Cell Physiology·Iwona Hirschler-LaszkiewiczBarbara A Miller
Feb 3, 2019·Journal of Cellular Physiology·Kah Keng WongSiti Muhamad Nur Husna
Sep 5, 2019·Cancers·Corinna J MohrRobert Lukowski
Dec 10, 2017·Oncotarget·Dominik KlumppStephan M Huber
Jun 21, 2020·Biomolecules·Tatjana VatterStephan M Huber
Jul 4, 2017·Nature Chemical Biology·Ralf FliegertAndreas H Guse
Apr 2, 2019·Frontiers in Immunology·Franziska EckertStephan M Huber
May 12, 2020·Frontiers in Pharmacology·Daniela PalmeStephan M Huber
Nov 30, 2018·Radiation and Environmental Biophysics·Anne-Laure PerraudFabienne Gally
Oct 24, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Peilin YuWei Yang
Mar 30, 2019·Cell Calcium·Barbara A Miller
Jun 9, 2021·Cell Death & Disease·Rui LinBaomin Shi
Jun 3, 2021·Biomolecules·Federica MaggiConsuelo Amantini

❮ Previous
Next ❯

Methods Mentioned

BETA
flow cytometry
Fluorescence
FCS
Dot blot

Software Mentioned

cBIOportal
InStat
Metafluor
GraphPad
FCS Express

Related Concepts

Related Feeds

BCL-2 Family Proteins

BLC-2 family proteins are a group that share the same homologous BH domain. They play many different roles including pro-survival signals, mitochondria-mediated apoptosis and removal or damaged cells. They are often regulated by phosphorylation, affecting their catalytic activity. Here is the latest research on BCL-2 family proteins.

Apoptosis in Cancer

Apoptosis is an important mechanism in cancer. By evading apoptosis, tumors can continue to grow without regulation and metastasize systemically. Many therapies are evaluating the use of pro-apoptotic activation to eliminate cancer growth. Here is the latest research on apoptosis in cancer.

Autophagy & Aging: Inhibitors

The feed focuses on the role of nuclear export inhibitors and their effect on autophagy and the aging process.

Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis

Calcium & Bioenergetics

Bioenergetic processes, including cellular respiration and photosynthesis, concern the transformation of energy by cells. Here is the latest research on the role of calcium in bioenergetics.

Cell Cycle Pathways

Cell cycle is a complex process regulated by several signal transduction pathways and enzymes. Here is the latest research on regulation of cell cycle and cell cycle pathways.