RRC ID 42592
Author Ishii M, Shimizu S, Hara Y, Hagiwara T, Miyazaki A, Mori Y, Kiuchi Y.
Title Intracellular-produced hydroxyl radical mediates H2O2-induced Ca2+ influx and cell death in rat beta-cell line RIN-5F.
Journal Cell Calcium
Abstract The melastatin-related transient receptor potential channel TRPM2 is a Ca(2+)-permeable channel that is activated by H(2)O(2), and the Ca(2+) influx through TRPM2 mediates cell death. However, the responsible oxidants for TRPM2 activation remain to be identified. In the present study, we investigated the involvement of hydroxyl radical on TRPM2 activation in TRPM2-expressing HEK293 cells and the rat beta-cell line RIN-5F. In both cell types, H(2)O(2) induced Ca(2+) influx in a concentration-dependent manner. However, the addition of hydroxyl radical, which was produced by mixing FeSO(4) and H(2)O(2), to the cells, did not increase intracellular Ca(2+) concentration. Interestingly, when H(2)O(2) was added to the cells under intracellular Fe(2+)-accumulated conditions, Ca(2+) influx was markedly enhanced compared to H(2)O(2) alone. In addition, the H(2)O(2)-induced Ca(2+) influx was reduced by hydroxyl radical scavengers and an iron chelator. Under intracellular Fe(2+)-accumulated conditions, H(2)O(2)-induced RIN-5F cell death through TRPM2 activation was also markedly enhanced. Hydroxyl radical scavengers and an iron chelator suppressed the RIN-5F cell death by H(2)O(2). These results strongly suggest that the intracellular hydroxyl radical plays a key role in the activation of TRPM2 during H(2)O(2) treatment, and TRPM2 activation mediated by hydroxyl radical is implicated in H(2)O(2)-induced cell death in the beta-cell line RIN-5F.
Volume 39(6)
Pages 487-94
Published 2006-6
DOI 10.1016/j.ceca.2006.01.013
PII S0143-4160(06)00018-2
PMID 16546253
MeSH Adenosine Triphosphate / pharmacology Animals Calcium / metabolism* Calcium Signaling / drug effects* Cell Death / drug effects Cell Line Free Radical Scavengers / pharmacology Humans Hydrogen Peroxide / pharmacology* Hydroxyl Radical / metabolism* Insulin-Secreting Cells / cytology* Insulin-Secreting Cells / drug effects* Iron Chelating Agents / pharmacology Potassium Chloride / pharmacology Rats TRPM Cation Channels / metabolism
IF 3.932
Times Cited 52
Human and Animal Cells