An antibiotic that inhibits protein and DNA synthesis
Anisomycin is a specific agonist of JNK with a concentration of 25 ng/ml [1].
JNK is short for c-Jun N-terminal kinase which reported as a proapoptotic kinase and plays an important role in many cellular events, such as cell cycle, proliferation, apoptosis and cell stress. It is also reported that JNK plays a pivotal role in the cell apoptosis induced by UV and activated JNK pathway could enhance TNF-α mediated apoptosis thus often regarded as a potent target in clinic [2] [3].
Anisomycin is a potent JNK agonist. When tested with hormone refractory cell line DU 145(highly resist to Fas mediated apoptosis), 250 ng/ml anisomysin treatment induced DU145 cells apoptosis together with Fas (200 ng/ml) via activating JNK [4]. In HL-60 cells, treatment of anisomysin activated JNK pathway activity which further induced cell apoptosis [5]. When tested with primary murine embryonic fibroblasts, anisomycin treatment stimulated cell apoptosis via activating JNK expression [6].
山霉素是JNK的特异性激动剂，浓度为25 ng/ml[1]。
JNK是c-Jun N-末端激酶的缩写，据报道，它是一种促凋亡激酶，在许多细胞事件中发挥重要作用，如细胞周期、增殖、凋亡和细胞应激。另据报道，JNK在紫外线诱导的细胞凋亡中起着关键作用，激活的JNK通路可增强TNF-α介导的细胞凋亡，因此在临床上常被视为一个有效的靶点[2][3]。
山霉素是一种强效JNK激动剂。当用激素难治性细胞系DU 145（对Fas介导的细胞凋亡具有高度抵抗力）进行测试时，250 ng/ml的异肌松处理通过激活JNK与Fas（200 ng/ml）一起诱导DU145细胞凋亡[4]。在HL-60细胞中，异肌松处理激活了JNK通路活性，从而进一步诱导细胞凋亡[5]。当用原代小鼠胚胎成纤维细胞测试时，山莨菪碱处理通过激活JNK表达刺激细胞凋亡[6]。
参考文献:
[1].? Jiang, J., et al., Spermassociated antigen 9 promotes astrocytoma cell invasion through the upregulation of podocalyxin. Mol Med Rep, 2014. 10(1): p. 417-22.
[2].? Lin, A., Activation of the JNK signaling pathway: breaking the brake on apoptosis. Bioessays, 2003. 25(1): p. 17-24.
[3].? Liu, J. and A. Lin, Role of JNK activation in apoptosis: a double-edged sword. Cell Res, 2005. 15(1): p. 36-42.
[4].? Curtin, J.F. and T.G. Cotter, Anisomycin activates JNK and sensitises DU 145 prostate carcinoma cells to Fas mediated apoptosis. Br J Cancer, 2002. 87(10): p. 1188-94.
[5].? Stadheim, T.A. and G.L. Kucera, c-Jun N-terminal kinase/stress-activated protein kinase (JNK/SAPK) is required for mitoxantrone- and anisomycin-induced apoptosis in HL-60 cells. Leuk Res, 2002. 26(1): p. 55-65.
[6].? Tournier, C., et al., Requirement of JNK for stress-induced activation of the cytochrome c-mediated death pathway. Science, 2000. 288(5467): p. 870-4.
Cell experiment: | PC-12 cells are seeded in 96-well plates at a concentration of 1×104 cells/well and cultured in an incubator at 37°C with 5% CO2 for at least 12 h prior to exposure to different concentrations of SP600125 (0-80 μM) or Anisomycin (0-20 μM) for 24 h. Subsequently, the culture medium is added to 20 μL of 5 mg/mL MTT working solution and the plate is incubated for 2 h at 37°C. The culture supernatant is removed and the formazan crystals are dissolved in 150 μL DMSO. Finally, the absorbance of each well is measured at 490 nm by a microplate reader. Cell viability is expressed as the percentage of the control group, which is set to 100%[1]. |
Animal experiment: | Mice[2]Adult male TNFRp55/p75 mice, adult male wild-type C57/BL and homozygous Nox2-/- mice are used in this study. Mice are randomized into six experimental groups that undergo the following treatments,. Animals are divided into six groups: group 1: control ischemia/reperfusion, wild-type mice are injected with DMSO (0.1 mL); group 2: Anisomycin+wild-type mice, wild-type mice are injected with Anisomycin (0.1 mg/kg ip); group 3: Anisomycin+TNFR p55/p75-/- mice, TNFR p55/75-/- mice are injected with Anisomycin (0.1 mg/kg ip); group 4: TNFR p55/p75-/- mice, TNFR p55/75-/- mice are not injected with Anisomycin; group 5: Anisomycin+Nox2-/- mice, Nox2-/- mice are injected with Anisomycin (0.1 mg/kg ip); and group 6: Nox2-/- mice, Nox2-/- mice are not injected with Anisomycin. Later (24 h), the hearts are subjected to 30 min of ischemia followed by 30 min of reperfusion[2]. |
参考文献: [1]. Lu Z, et al. Colistin-induced autophagy and apoptosis involves the JNK-Bcl2-Bax signaling pathway and JNK-p53-ROS positive feedback loop in PC-12 cells. | |
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