An inhibitor of mitochondrial dysfunction
Mitochonic acid 5 is an inhibitor of mitochondrial dysfunction.1 It increases intracellular ATP levels in Hep3B cells when used at a concentration of 3 ?M. Mitochonic acid 5 (5 ?M) rescues LPS-induced apoptosis and decreases in the mitochondrial membrane potential in BV-2 microglial cells.2 It protects against decreases in cell viability induced by L-buthionine-(S,R)-sulfoximine in fibroblasts isolated from patients with various mitochondrial diseases, including Leigh syndrome and Leber’s hereditary optic neuropathy (EC50s = 2.3-5.1 ?M), in an electron transport chain-independent manner.1 Mitochonic acid 5 (50 mg/kg) reduces plasma levels of creatinine and decreases acute renal tubular necrosis in a mouse model of bilateral retroperitoneal renal ischemia-reperfusion injury.3
1.Suzuki, T., Yamaguchi, H., Kikusato, M., et al.Mitochonic acid 5 (MA-5), a derivative of the plant hormone indole-3-acetic acid, improves survival of fibroblasts from patients with mitochondrial diseasesTohoku J. Exp. Med.236(3)225-232(2015) 2.Tan, J., Chen, S.-X., Lei, Q.-Y., et al.Mitochonic acid 5 regulates mitofusin 2 to protect microgliaNeural Regen. Res.16(9)1813-1820(2021) 3.Suzuki, T., Yamaguchi, H., Kikusato, M., et al.Mitochonic acid 5 binds mitochondria and ameliorates renal tubular and cardiac myocyte damageJ. Am. Soc. Nephrol.27(7)1925-1932(2016)
Cell experiment: | The mouse BV-2 cells used in this study are cultured in L-DMEM supplemented with 10% fetal bovine serum (FBS) at 37°C in an atmosphere with 5% CO2. To induce inflammatory injury, cells are treated with 10 ng/mL TNFα for about 12 h. Mitochonic acid 5 (0-10 μM) is incubated with BV-2 cells for about 12 h with TNFα treatment[2]. |
Animal experiment: | Mice[1]For evaluation of the blood concentrations of Mitochonic acid 5 (MA-5), Mitochonic acid 5 is orally administered at doses of 25, 50, or 150 mg/kg to C57/BL 6 mice, and blood samples are collected at the designated times. After 1 hour, the mice are euthanized. The blood concentration of Mitochonic acid 5 is determined by LC/MS/MS[1]. |
参考文献: [1]. Suzuki T, et al. Mitochonic Acid 5 Binds Mitochondria and Ameliorates Renal Tubular and Cardiac Myocyte Damage. J Am Soc Nephrol. 2016 Jul;27(7):1925-32. | |
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