Oxidative stress promotes redistribution of TRPM2 channels to the plasma membrane in hepatocytes

Ehsan Kheradpezhouh, Fiona H. Zhou, Greg J. Barritt, Grigori Y. Rychkov*

*Corresponding author for this work

    Research output: Contribution to journalArticlepeer-review

    14 Citations (Scopus)


    Transient Receptor Potential Melastatin (TRPM) 2 is a non-selective Ca 2+ permeable cation channel and a member of the Transient Receptor Potential (TRP) channel family. TRPM2 has unique gating properties; it is activated by intracellular ADP-ribose (ADPR), whereas Ca 2+ plays a role of an important co-factor in channel activation, increasing TRPM2 sensitivity to ADPR. TRPM2 is highly expressed in rat and mouse hepatocytes, where it has been shown to contribute to oxidative stress-induced cell death and liver damage due to paracetamol-overdose. The mechanisms regulating the activity of TRPM2 channels in hepatocytes, however, are not well understood. In this paper, we investigate the localisation of TRPM2 protein in hepatocytes. The presented results demonstrate that in rat hepatocytes under normal conditions, most of the TRPM2 protein is localised intracellularly. This was determined by confocal microscopy using TRPM2-and plasma membrane (PM)-specific antibodies and immunofluorescence, and biotinylation studies followed by western blotting. Interestingly, in hepatocytes treated with either H 2 O 2 or paracetamol, the amount of TRPM2 co-localised with PM is significantly increased, compared to the untreated cells. It is concluded that trafficking of TRPM2 to the PM could potentially contribute to a positive feedback mechanism mediating Ca 2+ overload in hepatocytes under conditions of oxidative stress.

    Original languageEnglish
    Pages (from-to)1891-1896
    Number of pages6
    JournalBiochemical and Biophysical Research Communications
    Issue number3
    Publication statusPublished - 10 Sept 2018


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