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A Simple and Inexpensive Method for Determining Cold Sensitivity and Adaptation in Mice
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TRPM2.

Malika Faouzi1, Reinhold Penner

  • 1Center for Biomedical Research, The Queen's Medical Center, 1301 Punchbowl Street, Honolulu, HI, 96813, USA, mfaouzi@hawaii.edu.

Handbook of Experimental Pharmacology
|April 24, 2014
PubMed
Summary
This summary is machine-generated.

Transient Receptor Potential Melastatin 2 (TRPM2) channels function as both ion channels and enzymes. Activated by calcium and ADP-ribose, TRPM2 plays roles in cell signaling and stress responses.

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Area of Science:

  • Biochemistry
  • Cell Biology
  • Physiology

Background:

  • TRPM2 is a cation channel in the TRPM family, expressed in various tissues including the brain and immune system.
  • It possesses both ion channel and ADP-ribose (ADPr) hydrolase enzymatic activities.
  • TRPM2 is localized to plasma and lysosomal membranes.

Purpose of the Study:

  • To elucidate the multifaceted roles and activation mechanisms of the TRPM2 channel.
  • To understand TRPM2's involvement in cellular signaling pathways.

Main Methods:

  • The study focuses on the biophysical and biochemical properties of TRPM2.
  • Investigated activation by intracellular molecules like ADP-ribose (ADPr) and Ca(2+).
  • Examined modulation by reactive oxygen species (ROS/NOS), cyclic ADPr, NAADP, and inhibitory factors such as acidic pH and AMP.

Main Results:

  • TRPM2 is activated synergistically by intracellular ADPr and Ca(2+).
  • Activation is also influenced by ROS/NOS, cyclic ADPr, and NAADP, and inhibited by acidic pH and AMP.
  • TRPM2 activation leads to increased intracellular Ca(2+) levels.

Conclusions:

  • TRPM2 mediates Ca(2+) signaling in inflammatory and secretory cells, influencing the release of mediators like cytokines, neurotransmitters, and insulin.
  • Under oxidative stress, TRPM2 activation can lead to cell death (apoptosis and necrosis).
  • TRPM2 is a key regulator of cellular responses to oxidative stress and signaling events.