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Title: H2O2-stimulated Ca2+ influx via TRPM2 is not the sole determinant of subsequent cell death
Authors: Wilkinson, Jenny A ×
Scragg, Jason L
Boyle, John P
Nilius, Bernd
Peers, Chris #
Issue Date: Mar-2008
Publisher: Springer-Verlag
Series Title: Pflügers Archiv: European Journal of Physiology vol:455 issue:6 pages:1141-1151
Abstract: Activation of transient receptor potential melastatin 2 (TRPM2), a non-selective, Ca2+-permeable cation channel, is implicated in cell death. Channel opening is stimulated by oxidative stress, a feature of numerous disease states. The wide expression profile of TRPM2 renders it a potentially significant therapeutic target in a variety of pathological settings including cardiovascular and neurodegenerative diseases. HEK293 cells transfected with human TRPM2 (HEK293/hTRPM2) were more vulnerable to H2O2-mediated cell death than untransfected controls in which H2O2-stimulated Ca2+ influx was absent. Flufenamic acid partially reduced Ca2+ influx in response to H2O2 but had no effect on viability. N-(p-Amylcinnamoyl) anthranilic acid substantially attenuated Ca2+ influx but did not alter viability. Poly(adenosine diphosphate ribose) polymerase inhibitors (N-(6-oxo-5,6-dihydro-phenanthridin-2-yl)-N,N-dimethylacetamide, 3,4-dihydro-5-[4-(1-piperidinyl)butoxy]-1(2H)-isoquinolinone and nicotinamide) reduced Ca2+ influx and provided a degree of protection but also had some protective effects in untransfected controls. These data suggest H2O2 triggers cell death in HEK293/hTRPM2 cells by a mechanism that is in part Ca2+ independent, as blockade of channel opening (evidenced by suppression of Ca2+ influx) did not correlate well with protection from cell death. Determining the underlying mechanisms of TRPM2 activation is pertinent in elucidating the relevance of this channel as a therapeutic target in neurodegenerative diseases and other pathologies associated with Ca2+ dysregulation and oxidative stress.
ISSN: 0031-6768
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Department of Cellular and Molecular Medicine - miscellaneous
Laboratory of Ion Channel Research
× corresponding author
# (joint) last author

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