Piericidin A是一种天然的线粒体NADH-泛醌氧化还原酶（复合物I）抑制剂。
Cas No.:2738-64-9
Sample solution is provided at 25 µL, 10mM.
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Piericidin A is a natural mitochondrial NADH-ubiquinone oxidoreductase (complex I) inhibitor [1]. Piericidin A is a potent neurotoxin and inhibits mitochondrial respiration by disrupting the electron transport system through its action on NADH-ubiquinone reductase[2]. Piericidin A has been widely used as a quorum-sensing inhibitor to suppress the expression of virulence genes in Erwinia carotovora subsp. atroseptica (Eca) [3].
In vitro, Piericidin A treatment for 48 hours significantly inhibited the viability of Tn5B1-4, HepG2, and Hek293 cells, with IC50 values of 0.061μM, 233.97μM, and 228.96μM, respectively[4]. Treatment of HT-29 cells with 100nM Piericidin A for 18 hours induced downregulation of GRP78 expression under low glucose conditions and was highly toxic to etoposide-resistant HT-29 cells[5]. Pretreatment with 100nM Piericidin A for 30min increased glucose uptake and consumption in C2C12 myoblasts without affecting Glut1 levels at the plasma membrane[6].
In vivo, Piericidin A treatment via a single intraperitoneal injection at a dose of 0.5mg/kg for 30min resulted in a significant reduction in partial pressure of arterial oxygen in mice[7]. Daily subcutaneous injection of Piericidin A at a dose of 0.5mg/kg for 28 days significantly increased pathologic phosphorylated tau levels in P301S+/+ mice and resulted in reduced cortical synaptic density[8].
References:
[1] Trost B M, Gholami H. Propene as an atom-economical linchpin for concise total synthesis of polyenes: piericidin A[J]. Journal of the American Chemical Society, 2018, 140(37): 11623-11626.
[2] Jeng M, Hall C, Crane F L, et al. Inhibition of mitochondrial electron transport by piericidin A and related compounds[J]. Biochemistry, 1968, 7(4): 1311-1322.
[3] Kang J E, Han J W, Jeon B J, et al. Efficacies of quorum sensing inhibitors, piericidin A and glucopiericidin A, produced by Streptomyces xanthocidicus KPP01532 for the control of potato soft rot caused by Erwinia carotovora subsp. atroseptica[J]. Microbiological research, 2016, 184: 32-41.
[4] Muhayimana S, Zhang X, Xu J, et al. Cytotoxic selectivity and apoptosis induction of piericidin A contributes potentially to its insecticidal effect against Mythimna separata (Lepidoptera: Noctuidae) larvae[J]. Pesticide Biochemistry and Physiology, 2019, 157: 19-25.
[5] Hwang J H, Kim J Y, Cha M R, et al. Etoposide‐resistant HT‐29 human colon carcinoma cells during glucose deprivation are sensitive to piericidin A, a GRP78 down‐regulator[J]. Journal of cellular physiology, 2008, 215(1): 243-250.
[6] Liemburg-Apers D C, Wagenaars J A L, Smeitink J A M, et al. Acute stimulation of glucose influx upon mitoenergetic dysfunction requires LKB1, AMPK, Sirt2 and mTOR–RAPTOR[J]. Journal of cell science, 2016, 129(23): 4411-4423.
[7] Schleifer G, Marutani E, Ferrari M, et al. Impaired hypoxic pulmonary vasoconstriction in a mouse model of Leigh syndrome[J]. American Journal of Physiology-Lung Cellular and Molecular Physiology, 2019, 316(2): L391-L399.
[8] Höllerhage M, Deck R, De Andrade A, et al. Piericidin A aggravates Tau pathology in P301S transgenic mice[J]. PLoS One, 2014, 9(12): e113557.
Piericidin A是一种天然的线粒体NADH-泛醌氧化还原酶（复合物I）抑制剂[1]。Piericidin A是一种强效神经毒素，通过作用于NADH-泛醌还原酶破坏电子传递系统，从而抑制线粒体呼吸[2]。Piericidin A已被广泛用作群体感应抑制剂，以抑制Erwinia carotovora subsp. atroseptica (Eca)中毒力基因的表达[3]。
在体外，Piericidin A处理48小时显著抑制了Tn5B1-4、HepG2和Hek293细胞的活力，IC50值分别为0.061µM、233.97µM和228.96µM[4]。使用100nM的Piericidin A处理HT-29细胞18小时，在低葡萄糖条件下诱导了GRP78表达的下调，并对依托泊苷耐药的HT-29细胞具有高毒性[5]。用100nM的Piericidin A预处理30分钟，增加了C2C12成肌细胞的葡萄糖摄取和消耗，而不影响质膜上的Glut1水平[6]。
在体内，单次腹腔注射0.5mg/kg剂量的Piericidin A 30分钟，导致小鼠动脉血氧分压显著降低[7]。每日皮下注射0.5mg/kg剂量的Piericidin A，持续28天，显著增加了P301S+/+小鼠的病理性磷酸化tau蛋白水平，并导致皮层突触密度降低[8]。
| Cell experiment [1]: | |
Cell lines | Tn5B1-4 cells |
Preparation Method | Tn5B1-4 cells were cultured in TNM-FH medium at 28°C in 5% (v/v) CO2 to 70% confluency. 1×105 cells/ml were seeded in 96-well plates (100μl per well) and cultured for 8h. Tn5B1-4 cells were exposed to 0.02, 0.04, 0.08, 0.16, and 0.32μM Piericidin A, and cell viability was measured 48h later. |
Reaction Conditions | 0.02, 0.04, 0.08, 0.16, and 0.32μM; 48h |
Applications | Piericidin A treatment reduced the cell viability of Tn5B1-4 cells in a dose-dependent manner. |
| Animal experiment [2]: | |
Animal models | P301S transgenic mice (C57BL/6J mice) |
Preparation Method | P301S transgenic mice (12 weeks of age) were housed in a specific pathogen-free (SPF) animal house maintained at 23°C with a 12h light/dark cycle and free access to water and food. The average weight of the animals was 28g. Mice were anaesthetized by intraperitoneal (i.p.) injection of ketamine (10mg/kg) and xylazine (20mg/kg) diluted in saline. Then, a small skin cut was made in the neck region of the mice, and anatomical forceps were used to open a subcutaneous pocket in the back of the mice. Osmotic minipumps were placed in this skin pocket, and the skin was sutured. Mice were injected subcutaneously with Piericidin A (0.5mg/kg/day) for 28 consecutive days, and then the brain tissues were collected for analysis. |
Dosage form | 0.5mg/kg/day for 28 days; s.c. |
Applications | Piericidin A treatment increased levels of pathologically phosphorylated tau in P301S transgenic mice. |
References: | |
| Cas No. | 2738-64-9 | SDF | |
| 别名 | 粉蝶霉素A,AR 054, Shaoguanmycin B, SN 198E | ||
| 化学名 | 2-[(2E,5E,7E,11E)-10R-hydroxy-3,7,9R,11-tetramethyl-2,5,7,11-tridecatetraen-1-yl]-5,6-dimethoxy-3-methyl-4-pyridinol | ||
| Canonical SMILES | COC1=C(O)C(C)=C(C/C=C(C)/C/C=C/C(C)=C/[C@H]([C@@H](O)/C(C)=C/C)C)N=C1OC | ||
| 分子式 | C25H37NO4 | 分子量 | 415.6 |
| 溶解度 | Soluble in DMSO, Soluble in DMF, Soluble in Ethanol, Soluble in Methanol | 储存条件 | Store at -80°C,protect from light |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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1 mg | 5 mg | 10 mg |
| 1 mM | 2.4062 mL | 12.0308 mL | 24.0616 mL |
| 5 mM | 481.2 μL | 2.4062 mL | 4.8123 mL |
| 10 mM | 240.6 μL | 1.2031 mL | 2.4062 mL |
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| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
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| % DMSO % % Tween 80 % saline | ||||||||||
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2.
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