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PMID: 15952035 Published · ppublish English Journal Article Review

TRPM2: a calcium influx pathway regulated by oxidative stress and the novel second messenger ADP-ribose.

Pflugers Archiv : European journal of physiology ·Vol. 451 ·No. 1 ·2005-10-00 ·Pages 212-9

Kühn FJ, Heiner I, Lückhoff A

Abstract

A unique functional property within the transient receptor potential (TRP) family of cation channels is the gating of TRP (melastatin) 2 (TRPM2) channels by ADP-ribose (ADPR). ADPR binds to the intracellular C-terminal tail of TRPM2, a domain that shows homology to enzymes with pyrophosphatase activity. Cytosolic Ca(2+) enhances TRPM2 gating by ADPR; ADPR and Ca(2+) in concert may be an important messenger system mediating Ca(2+) influx. Other stimuli of TRPM2 include NAD and H(2)O(2) and cyclic ADPR, which may act synergistically with ADPR. H(2)O(2), an experimental paradigm of oxidative stress, may also induce the formation of ADPR in the nucleus or mitochondria. In this review, we summarize the gating properties of TRPM2 and the proposed pathways of channel activation in vivo. TRPM2 is likely to be a key player in several signalling pathways, mediating cell death in response to oxidative stress or in reperfusion injury. Moreover, it plays a decisive role in experimentally induced diabetes mellitus and in the activation of leukocytes.

MeSH Terms
Adenosine Diphosphate Ribose/physiology Animals Calcium/metabolism Cyclic ADP-Ribose/physiology Drug Synergism Humans Hydrogen Peroxide/pharmacology Oxidative Stress/physiology Poly(ADP-ribose) Polymerases/physiology Second Messenger Systems/physiology TRPM Cation Channels/chemistry,drug effects,genetics,physiology
Chemicals
TRPM Cation Channels TRPM2 protein, human Cyclic ADP-Ribose Adenosine Diphosphate Ribose Hydrogen Peroxide Poly(ADP-ribose) Polymerases Calcium
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Kühn Frank J P
Medical Faculty, RWTH Aachen, Institute of Physiology, Pauwelsstrasse 30, 52057 Aachen, Germany.
Heiner Inka
Lückhoff Andreas
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Article Info
Journal
Pflugers Archiv : European journal of physiology
Abbr.
Pflugers Arch
ISSN
0031-6768
DOI
10.1007/s00424-005-1446-y
Published
2005-10-00
Epub
2005-00-11
Pages
212-9
Language
English
Region
Germany
NLM ID
0154720
Subset
IM
External Links
PubMed source DOI: 10.1007/s00424-005-1446-y View journal details
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