These tools will no longer be maintained as of December 31, 2024. Archived website can be found here. PubMed4Hh GitHub repository can be found here. Contact NLM Customer Service if you have questions.


Pubmed for Handhelds

PUBMED FOR HANDHELDS

Search MEDLINE/PubMed

  • Title: H2O 2-stimulated Ca2+ influx via TRPM2 is not the sole determinant of subsequent cell death.
    Author: Wilkinson JA, Scragg JL, Boyle JP, Nilius B, Peers C.
    Journal: Pflugers Arch; 2008 Mar; 455(6):1141-51. PubMed ID: 18043941.
    Abstract:
    Activation of transient receptor potential melastatin 2 (TRPM2), a non-selective, Ca(2+)-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 H(2)O(2)-mediated cell death than untransfected controls in which H(2)O(2)-stimulated Ca(2+) influx was absent. Flufenamic acid partially reduced Ca(2+) influx in response to H(2)O(2) but had no effect on viability. N-(p-Amylcinnamoyl) anthranilic acid substantially attenuated Ca(2+) 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 Ca(2+) influx and provided a degree of protection but also had some protective effects in untransfected controls. These data suggest H(2)O(2) triggers cell death in HEK293/hTRPM2 cells by a mechanism that is in part Ca(2+) independent, as blockade of channel opening (evidenced by suppression of Ca(2+) 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 Ca(2+) dysregulation and oxidative stress.
    [Abstract] [Full Text] [Related] [New Search]