Rotenone|83-79-4|安捷凯

Background

Rotenone is an inhibitor of the mitochondrial complex I electron transport chain with IC50 value of 1.7 - 2.2 μM.

Electron transport chain (ETC) is a series of compounds that transfer electrons from electron donors to electron acceptors and transfer protons (H+ ions) across a membrane. The proton gradient drives ATP synthesis. Complex I is one of the main sites of production of superoxide.

Rotenone is an inhibitor of the mitochondrial complex I electron transport chain. In the transformed cell line HEK 293 and cancer cell lines U87, rotenone (50 μM) induced cell death by 30% and 40% respectively in a dose dependent way, which was mediated by reactive oxygen species (ROS). Also, rotenone significantly induced autophagy formation [1]. In SH-SY5Y cells, rotenone induced cell apoptosis in a caspase-dependent way. Also, rotenone induced phosphorylation of p38 MAP kinase, c-Jun and JNK, which indicated activation of the p38 and JNK pathways [2]. In differentiated SH-SY5Y neuroblastoma cells, rotenone (50 nM) induced cell death by 60% and slowed mitochondrial movement. While rotenone didn’t induce the formation of resembling Lewy bodies [3].

鱼藤酮是线粒体复合物I电子传输链的抑制剂，IC50值为1.7-2.2μM。

电子传输链（ETC）是一系列将电子从电子供体转移到电子受体并在膜上转移质子（H+离子）的化合物。质子梯度驱动ATP合成。复合体I是产生超氧化物的主要位点之一。

鱼藤酮是线粒体复合体I电子传递链的抑制剂。在转化细胞系HEK 293和癌症细胞系U87中，鱼藤酮（50μM）以活性氧（ROS）介导的剂量依赖性方式分别诱导30%和40%的细胞死亡。此外，鱼藤酮显著诱导自噬形成[1]。在SH-SY5Y细胞中，鱼藤酮以胱天蛋白酶依赖的方式诱导细胞凋亡。此外，鱼藤酮诱导p38 MAP激酶、c-Jun和JNK的磷酸化，这表明p38和JNK途径被激活[2]。在分化的SH-SY5Y神经母细胞瘤细胞中，鱼藤酮（50nM）诱导细胞死亡60%，并减缓线粒体运动。而鱼藤酮没有诱导类似路易体的形成[3]。

参考文献:
[1].? Chen Y, McMillan-Ward E, Kong J, et al. Mitochondrial electron-transport-chain inhibitors of complexes I and II induce autophagic cell death mediated by reactive oxygen species. J Cell Sci, 2007, 120(Pt 23): 4155-4166.
[2].? Newhouse K, Hsuan SL, Chang SH, et al. Rotenone-induced apoptosis is mediated by p38 and JNK MAP kinases in human dopaminergic SH-SY5Y cells. Toxicol Sci, 2004, 79(1): 137-146.
[3].? Borland MK, Trimmer PA, Rubinstein JD, et al. Chronic, low-dose rotenone reproduces Lewy neurites found in early stages of Parkinson's disease, reduces mitochondrial movement and slowly kills differentiated SH-SY5Y neural cells. Mol Neurodegener, 2008, 3: 21.

Protocol

Cell experiment [1]:

Cell lines

differentiated SH-SY5Y neuroblastoma cells

Preparation method

The solubility of this compound in DMSO is ≥77.6mg/mL. General tips for obtaining a higher concentration: Please warm the tube at 37℃ for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below -20℃ for several months.

Reacting condition

50 nM; 21 days

Applications

In differentiated SH-SY5Y neuroblastoma cells, Rotenone (50 nM) produced a biphasic survival curve with ~40% loss by 6 days and a second decline to ~60% loss between 18 and 21 days. Mitochondrial movement velocities were reduced at 8 days.

Animal experiment [2]:

Animal models

20–25-weekold female BALB/c mice

Dosage form

(rotenone: 0.35 mg/kg; DMSO: 9.86 mg/kg) or vehicle (DMSO: 9.86 mg/kg); injected into the right-side nasal cavity of mice; once a day for 2 weeks

Application

In mice, rotenone attenuated the olfactory function and retarded the inhibitory input into the mitral cells, which are output neurons in the olfactory bulb (OB). Rotenone also caused neurite degeneration of DA neurons in the substantia nigra.

Other notes

Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal.

参考文献:

[1]. Borland MK, Trimmer PA, Rubinstein JD, et al. Chronic, low-dose rotenone reproduces Lewy neurites found in early stages of Parkinson's disease, reduces mitochondrial movement and slowly kills differentiated SH-SY5Y neural cells. Mol Neurodegener, 2008, 3: 21.

[2]. Sasajima H1, Miyazono S, Noguchi T, et al. Intranasal Administration of Rotenone to Mice Induces Dopaminergic Neurite Degeneration of Dopaminergic Neurons in the Substantia Nigra. Biol Pharm Bull. 2017;40(1):108-112.

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