8-Br-ADPR disodium (8-Bromoadenosine-5'-O-diphosphoribose) is a TRPM2 inhibitor and ADPR signaling pathway antagonist. 8-Br-ADPR disodium inhibits glucagon-mediated nuclear calcium signaling and downstream CaMKII/CREB phosphorylation by blocking ADPR-induced TRPM2 activation. 8-Br-ADPR disodium significantly reduces gluconeogenic gene expression and blood glucose levels in diabetic models. 8-Br-ADPR disodium effectively blocks ADPR -mediated calcium signal transduction in NK cells, inhibits immune synapse formation, granzyme B release and cytolytic activity against melanoma cells. 8-Br-ADPR disodium is widely used in studies related to diseases such as diabetes, melanoma and lymphoma [1] [2].
In Vivo, 8-Br-ADPR (32 mg/kg; i.v.; single dose) disodium reduces fasting and pyruvate-induced blood glucose levels in wild-type mice by inhibiting hepatic gluconeogenic gene expression and CRE-mediated transcriptional activity[1]. 8-Br-ADPR (32 mg/kg; i.v.; single dose) disodium reduces pyruvate-induced blood glucose levels in diabetic db/db mice by inhibiting hepatic gluconeogenic gene expression and CRE-mediated transcriptional activity[1].
In Vitro, 8-Br-ADPR (100 μM; preincubated prior to glucagon treatment) disodium specifically blocks glucagon-induced sustained nuclear calcium signals in mouse primary hepatocytes, without altering cytosolic calcium signals[1]. 8-Br-ADPR (100 μM; 30 min preincubated before ADPR treatment) disodium completely blocks ADPR-induced calcium flux between the perinuclear space and nucleoplasm in isolated nuclei from mouse primary hepatocytes[1]. 8-Br-ADPR (100 μM; 30 min preincubated before 100 nM glucagon treatment for 4 h) disodium significantly reduces glucagon-induced G6pc and Pck1 mRNA expression in mouse primary hepatocytes[1]. 8-Br-ADPR (100 μM; 20 min) disodium inhibits B16F10-induced translocation of perforin and granzyme B to the immunological synapse in murine NK cells[2]. 8-Br-ADPR (100 μM; 20 min) disodium reduces the cytolytic activity of murine NK cells against B16F10 melanoma target cells[2].
References:
[1]. Rah SY, et al. CD38/ADP-ribose/TRPM2-mediated nuclear Ca 2+ signaling is essential for hepatic gluconeogenesis in fasting and diabetes. Exp Mol Med. 2023;55(7):1492-1505.
[2]. Rah S Y, et al. ADP-ribose/TRPM2-mediated Ca2+ signaling is essential for cytolytic degranulation and antitumor activity of natural killer cells[J]. Scientific reports, 2015, 5(1): 9482.
In Vivo, 8-Br-ADPR (32 mg/kg; i.v.; single dose) disodium reduces fasting and pyruvate-induced blood glucose levels in wild-type mice by inhibiting hepatic gluconeogenic gene expression and CRE-mediated transcriptional activity[1]. 8-Br-ADPR (32 mg/kg; i.v.; single dose) disodium reduces pyruvate-induced blood glucose levels in diabetic db/db mice by inhibiting hepatic gluconeogenic gene expression and CRE-mediated transcriptional activity[1].
In Vitro, 8-Br-ADPR (100 μM; preincubated prior to glucagon treatment) disodium specifically blocks glucagon-induced sustained nuclear calcium signals in mouse primary hepatocytes, without altering cytosolic calcium signals[1]. 8-Br-ADPR (100 μM; 30 min preincubated before ADPR treatment) disodium completely blocks ADPR-induced calcium flux between the perinuclear space and nucleoplasm in isolated nuclei from mouse primary hepatocytes[1]. 8-Br-ADPR (100 μM; 30 min preincubated before 100 nM glucagon treatment for 4 h) disodium significantly reduces glucagon-induced G6pc and Pck1 mRNA expression in mouse primary hepatocytes[1]. 8-Br-ADPR (100 μM; 20 min) disodium inhibits B16F10-induced translocation of perforin and granzyme B to the immunological synapse in murine NK cells[2]. 8-Br-ADPR (100 μM; 20 min) disodium reduces the cytolytic activity of murine NK cells against B16F10 melanoma target cells[2].
References:
[1]. Rah SY, et al. CD38/ADP-ribose/TRPM2-mediated nuclear Ca 2+ signaling is essential for hepatic gluconeogenesis in fasting and diabetes. Exp Mol Med. 2023;55(7):1492-1505.
[2]. Rah S Y, et al. ADP-ribose/TRPM2-mediated Ca2+ signaling is essential for cytolytic degranulation and antitumor activity of natural killer cells[J]. Scientific reports, 2015, 5(1): 9482.