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Ionomycin calcium salt

(Synonyms: 罗红霉素钙盐(链霉菌属载体),SQ23377 calcium) 目录号 : GC15148

Ionomycin calcium salt是一种窄谱抗生素,对革兰氏阳性菌具有活性,由丛生链霉菌(Streptomyces conglobatus)产生。

Ionomycin calcium salt Chemical Structure

Cas No.:56092-82-1

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Sample solution is provided at 25 µL, 10mM.

Description

Ionomycin calcium salt is a narrow spectrum antibiotic being active against Gram-positive bacteria, which produced by the bacterium Streptomyces conglobatus[1]. Ionomycin calcium salt promotes apoptosis. Ionomycin also induces the activation of protein kinase C (PKC)[2].

In vitro, treatment with 2 µM Ionomycin in LCLC 103H cells results in an instantaneous increase in intracellular Ca2+ concentration from 50 to 180 nM. And in Ionomycin-treated cultures, there is obvious DNA fragmentation and PARP cleavage to an 85-kDa fragment, and necrosis could be detected in ~1-5% of the Ionomycin treated cells[2]. In ras oncogene expressing cells, Ionomycin leads to a dose dependent increase of intracellular calcium activity. At 100 nmol/l ionomycin intracellular calcium is increased from 114 ± 17 nmol/l to 342 ± 24 nmol/l, a value within the range of intracellular calcium concentrations following application of bradykinin[3].

In vivo efficacy test, treatment with 1 µm ionomycin for 6 h, ubiquitination of ENaC-β was robustly enhanced in cells overexpressing wild-type Nedd4-2a[4].

References:
[1] Liu WC, et al. Ionomycin, a new polyether antibiotic. J Antibiot (Tokyo). 1978 Sep;31(9):815-9.
[2] Chatila T, et al. Mechanisms of T cell activation by the calcium ionophore ionomycin. J Immunol. 1989 Aug 15;143(4):1283-9.
[3] WÖll E, et al. The role of calcium in cell shrinkage and intracellular alkalinization by bradykinin in Ha-ras oncogene expressing cells. FEBS Lett. 1993 May 17;322(3):261-5.
[4] Wang J, et al. Calcium activates Nedd4 E3 ubiquitin ligases by releasing the C2 domain-mediated auto-inhibition. J Biol Chem. 2010 Apr 16;285(16):12279-88.

Ionomycin calcium salt是一种窄谱抗生素,对革兰氏阳性菌具有活性,由丛生链霉菌(Streptomyces conglobatus)产生[1]。Ionomycin calcium salt可促进细胞凋亡。Ionomycin calcium salt还能诱导激活蛋白激酶 C (PKC)[2]。

在体外,用 2 µM Ionomycin calcium sal处理 LCLC 103H 细胞,细胞内 Ca2+ 浓度会瞬间从 50 nM 增至 180 nM。在经Ionomycin calcium sal处理的培养物中,会出现明显的 DNA 断裂和 PARP 分裂,形成 85 kDa 的片段,在约 1-5% 经Ionomycin calcium sal处理的细胞中可检测到坏死[2]。在表达ras癌基因的细胞中,Ionomycin calcium sal会导致细胞内钙活性的剂量依赖性增加。当Ionomycin calcium sal浓度为 100 nmol/l 时,细胞内钙的浓度从 114 ± 17 nmol/l 增至 342 ± 24 nmol/l,这一数值在使用缓激肽后细胞内钙浓度的范围内[3]。

在体内药效试验中,用 1 µm Ionomycin calcium sal处理 6 小时后,在过表达野生型 Nedd4-2a 的细胞中,ENaC-β 的泛素化显著增强[4]。

实验参考方法

Cell experiment [1]:

Cell lines

N1E-115 cells

Preparation Method

Cells were treated with various concentrations (0, 0.2, 0.5, 1, 2, and 10 µM) and incubation times (3, 6, 12, and 24 h) of ionomycin, and cell survival was determined using the trypan blue dye exclusion assay.

Reaction Conditions

0, 0.2, 0.5, 1, 2, and 10 µM;3, 6, 12, and 24 h

Applications

Ionomycin treatment induced cell death in a concentration- and time-dependent manner.

Animal experiment [2]:

Animal models

Adult male C57BL/6 wild type (20-25 g, 8-10 weeks old) and FXR KO mice (20-25 g, 8-10 weeks old)

Preparation Method

In order to investigate the biological function of FXR in vivo, an L-type calcium channel agonist, Bayk8644 (2 mg/kg) was given intraperitoneally at 10 min after reperfusion. Bayk8644 stock solution (1 mmol/L in dimethyl sulfoxide, DMSO) was diluted in 1× phosphate-buffered saline (PBS) with a final DMSO concentration of 4.6%. Similarly, PBS with 4.6% DMSO was given intraperitoneally in sham, wild-type vehicle, and FXR knockout vehicle groups as control. A dose range of ionomycin (50 nmol/L), GW4064 (0, 1, 1.5, 3, and 6 µmol/L), or Z-guggulsterone (Z-GS, 0, 2.5, 5, and 10 µmol/L) was given for 18 h before oxygen and glucose deprivation (OGD).

Dosage form

50 nmol/L (4.6% DMSO); 18 h; i.p.

Applications

TUNEL staining demonstrated that Z-GS treatment reduced neuronal apoptosis and addition of IM (Ionomycin) significantly increased apoptotic neurons compared to OGD group, suggesting that inhibition of FXR (Farnesoid X receptor) can reduce neuronal apoptosis through reducing calcium influx after OGD/R.

References:

Nakamura S, et al. Ionomycin-induced calcium influx induces neurite degeneration in mouse neuroblastoma cells: analysis of a time-lapse live cell imaging system. Free Radic Res. 2016;50(11):1214-1225.
Shan HM, et al. Farnesoid X receptor knockout protects brain against ischemic injury through reducing neuronal apoptosis in mice. J Neuroinflammation. 2020 May 25;17(1):164.

化学性质

Cas No. 56092-82-1 SDF
别名 罗红霉素钙盐(链霉菌属载体),SQ23377 calcium
化学名 calcium (4S,6S,8S,10E,12R,14R,16E,18S,19S,20R,21S)-19,21-dihydroxy-22-((2R,2'R,5R,5'S)-5'-((R)-1-hydroxyethyl)-2,5'-dimethyloctahydro-[2,2'-bifuran]-5-yl)-4,6,8,12,14,18,20-heptamethyl-11-oxido-9-oxodocosa-10,16-dienoate
Canonical SMILES O[C@H](C)[C@@]1(C)O[C@H](CC1)[C@]2(C)O[C@@H](C[C@@H]([C@@H](C)[C@H]([C@H](/C=C/C[C@@H](C)C[C@@H](C)/C([O-])=C\C([C@@H](C)C[C@@H](C)C[C@@H](C)CCC([O-])=O)=O)C)O)O)CC2.[Ca+2]
分子式 C41H70O9.Ca 分子量 747.08
溶解度 20mg/mL in enathol, 1.6mg/mL in DMSO, 1.2mg/mL in DMF 储存条件 Store at -20°C,protect from light
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1 mM 1.3385 mL 6.6927 mL 13.3854 mL
5 mM 0.2677 mL 1.3385 mL 2.6771 mL
10 mM 0.1339 mL 0.6693 mL 1.3385 mL
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