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Adenosine 5′-diphosphoribose sodium (ADP ribose sodium) is a nicotinamide adenine nucleotide (NAD+) metabolite. Adenosine 5′-diphosphoribose sodium is the most potent and primary intracellular Ca2+-permeable cation TRPM2 channel activator. Adenosine 5′-diphosphoribose sodium also can enhance autophagy[1][2].

In mouse embryonic fibroblasts (MEFs), H2O2 treatment demonstrates that the activation of poly(ADP-ribose) (PAR) polymerase-1 (PARP-1) produced Adenosine 5′-diphosphoribose (ADP ribose), which is an activating signal for TRPM2 channels, thereby promoting Ca2+ elevation through extracellular Ca2+ influx and (or) lysosomal Ca2+ release. This process eventually activates early or late autophagy in response to different degrees of oxidative stress[1][1].

TRPM2 channels are activated by binding of Adenosine 5′-diphosphoribose (ADP ribose) to the intracellular NUDT9-homology (NUDT9-H) domain unique to TRPM2 and located at its C terminus. In addition to ADPR, intracellular Ca2+ is an essential coactivator: TRPM2 channels open only in the combined presence of both ligands[2].

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