-dependent neuronal death in a similar concentration range. Molecular cloning of TRPM2 cDNA from rat brain revealed several differences in amino acid sequences within the Nudix box region as compared with those of human and mouse TRPM2. ADPR-induced current responses, H 2 O 2 -induced Ca 2+ influx, and H 2 O 2 -induced cell death were induced in human embryonic kidney cells heterologously expressing rat TRPM2. Treatment of cultured neurons with small interfering RNA against rat TRPM2, which efficiently suppressed immunoreactive TRPM2 content and the H 2 O 2 -induced Ca 2+ influx, significantly inhibited H 2 O 2 -induced neuronal death. These results suggest that TRPM2 plays a pivotal role in H 2 O 2 -induced neuronal death as redox-sensitive Ca
2+-permeable channels expressed in neurons.
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