Mitoquinone mesylate (Mitoquinone methanesulfonate)
(Synonyms: 米托蒽醌甲磺酸盐; MitoQ mesylate; MitoQ10 mesylate) 目录号 : GC31292
甲磺酸对苯二酚（Mitoquinone mesylate (Mitoquinone methanesulfonate)甲磺酸对醌）是广泛使用的针对线粒体的抗氧化剂之一。
Cas No.:845959-50-4
Sample solution is provided at 25 µL, 10mM.
Quality Control & SDS
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- Purity: >98.00%
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| Cell experiment [1]: | |
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Cell lines |
HSC-T6 cells |
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Preparation Method |
Mitoquinone mesylate was added directly to the culture medium at final concentrations of 2 µM, 20 µM, 13 µM, 50 nM, or 10 µM, respectively, for 24 h. |
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Reaction Conditions |
2 µM, 20 µM, 13 µM, 50 nM, or 10 µM for 24 hours |
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Applications |
Confocal fluorescence microscopy showed that mitoquinone mesylate treatment reversed fragmented mitochondria in active HSCs to an elongated state. Immunoblot analysis showed significantly downregulated Fis1 and Drp1 after mitoquinone mesylate treatment. |
| Animal experiment [2]: | |
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Animal models |
male Wistar rats |
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Preparation Method |
For pharmacokinetic study, groups of rats (n = 4-5) were administered either an intravenous (IV) dose (5 mg/kg) via the cannula or an oral dose (25 mg/kg) by gavage. |
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Dosage form |
Intravenous injection, 5 mg/kg; oral, 25 mg/kg. |
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Applications |
After oral administration, mitoquinone mesylate was rapidly absorbed giving a plasma concentration of about 25 ng/mL after about 1 h. Thereafter, mitoquinone mesylate concentration fluctuated reaching a maximum (Cmax) of 31.2 ± 6.9 ng/mL at 4.0 h. After IV administration, the plasma concentration of mitoquinone mesylate exhibited an exponential decline with a rapid distribution phase followed by a slower elimination phase |
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References: [1]: Zhou Y, Long D, Zhao Y, et al. Oxidative stress-mediated mitochondrial fission promotes hepatic stellate cell activation via stimulating oxidative phosphorylation[J]. Cell death & disease, 2022, 13(8): 1-15. |
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Mitoquinone mesylate (Mitoquinone methanesulfonate) is among the widely used antioxidants that target the mitochondria. It was developed to readily penetrate the BBB and neuronal membranes, where it is concentrated into several hundred-folds within the mitochondria where it mediates the local anti-oxidative capacity [1]. Within the ETC, complex II, also known as succinate dehydrogenase, reduces Mitoquinone mesylate ubiquinone moiety to the active antioxidant ubiquinol which scavenges excess ROS [2].
Mitoquinone mesylate (50 nM) reduced 6-OHDA-induced mitochondrial fragmentation, when used in SH-SY5Y cell line. It inhibited mitochondrial fission protein and the translocation of pro-apoptotic protein (Bax) in the mitochondria [3].
Mitoquinone mesylate treatment inhibited the loss of dopaminergic neurons and enhanced behavioral performance, showed neuroprotective effects in mouse models of PD [4]. Mitoquinone mesylate treatment enhanced the fine motor control and reduced markers of oxidative damage in muscles in a Huntington's disease (HD) mouse model [5]. Mitoquinone mesylate reduced white matter injury, improved neurological performance, and decreased motor-evoked potential latency in intracerebral hemorrhagic (ICH) mice [6].
References:
[1]. Murphy M P, Smith R A J. Targeting antioxidants to mitochondria by conjugation to lipophilic cations[J]. Annu. Rev. Pharmacol. Toxicol., 2007, 47: 629-656.
[2]. James A M, Cochemé H M, Smith R A J, et al. Interactions of Mitochondria-targeted and Untargeted Ubiquinones with the Mitochondrial Respiratory Chain and Reactive Oxygen Species: IMPLICATIONS FOR THE USE OF EXOGENOUS UBIQUINONES AS THERAPIES AND EXPERIMENTAL TOOLS. Journal of Biological Chemistry, 2005, 280(22): 21295-21312.
[3]. Solesio M E, Prime T A, Logan A, et al. The mitochondria-targeted anti-oxidant MitoQ reduces aspects of mitochondrial fission in the 6-OHDA cell model of Parkinson's disease[J]. Biochimica et Biophysica Acta (BBA)-Molecular Basis of Disease, 2013, 1832(1): 174-182.
[4]. Pinho B R, Duarte A I, Canas P M, et al. The interplay between redox signalling and proteostasis in neurodegeneration: In vivo effects of a mitochondria-targeted antioxidant in Huntington's disease mice[J]. Free Radical Biology and Medicine, 2020, 146: 372-382.
[5]. Pinho B R, Duarte A I, Canas P M, et al. The interplay between redox signalling and proteostasis in neurodegeneration: In vivo effects of a mitochondria-targeted antioxidant in Huntington's disease mice[J]. Free Radical Biology and Medicine, 2020, 146: 372-382.
[6]. Chen W, Guo C, Jia Z, et al. Inhibition of mitochondrial ROS by MitoQ alleviates white matter injury and improves outcomes after intracerebral haemorrhage in mice[J]. Oxidative medicine and cellular longevity, 2020, 2020.
Mitoquinone mesylate（Mitoquinone methanesulfonate）是广泛使用的靶向线粒体的抗氧化剂之一。它被开发成很容易穿透 BBB 和神经元膜，在那里它在线粒体中浓缩成数百倍，在线粒体中调节局部抗氧化能力 [1]。在 ETC 中，复合物 II（也称为琥珀酸脱氢酶）将甲磺酸丝裂醌泛醌部分还原为活性抗氧化剂泛醇，后者清除过量的 ROS [2]。
当用于 SH-SY5Y 细胞系时，Mitoquinone mesylate (50 nM) 减少了 6-OHDA 诱导的线粒体断裂。抑制线粒体分裂蛋白和促凋亡蛋白（Bax）在线粒体中的转位[3]。
Mitoquinone mesylate 治疗抑制了多巴胺能神经元的损失并增强了行为表现，在 PD 小鼠模型中显示出神经保护作用 [4]。在亨廷顿舞蹈症 (HD) 小鼠模型中，甲磺酸米托醌治疗增强了精细运动控制并减少了肌肉氧化损伤的标志物[5]。甲磺酸米托醌减少了脑出血 (ICH) 小鼠的白质损伤，改善了神经功能，并减少了运动诱发电位潜伏期 [6]。
| Cas No. | 845959-50-4 | SDF | |
| 别名 | 米托蒽醌甲磺酸盐; MitoQ mesylate; MitoQ10 mesylate | ||
| Canonical SMILES | [O-]S(=O)(C)=O.O=C(C(CCCCCCCCCC[P+](C1=CC=CC=C1)(C2=CC=CC=C2)C3=CC=CC=C3)=C4C)C(OC)=C(OC)C4=O | ||
| 分子式 | C38H47O7PS | 分子量 | 678.81 |
| 溶解度 | DMSO : 50 mg/mL (73.66 mM);Water : < 0.1 mg/mL (insoluble) | 储存条件 | Store at -20°C |
| 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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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 1.4732 mL | 7.3658 mL | 14.7317 mL |
| 5 mM | 0.2946 mL | 1.4732 mL | 2.9463 mL |
| 10 mM | 0.1473 mL | 0.7366 mL | 1.4732 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 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 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
Mitoquinone mesylate (MitoQ) prevents sepsis-induced diaphragm dysfunction
J Appl Physiol (1985)2021 Aug 1;131(2):778-787.PMID: 34197233DOI: 10.1152/japplphysiol.01053.2020
Sepsis-induced diaphragm dysfunction is a major contributor to respiratory failure in mechanically ventilated patients. There are no pharmacological treatments for this syndrome, but studies suggest that diaphragm weakness is linked to mitochondrial free radical generation. We hypothesized that administration of Mitoquinone mesylate (MitoQ), a mitochondrially targeted free radical scavenger, would prevent sepsis-induced diaphragm dysfunction. We compared diaphragm function in 4 groups of male mice: 1) sham-operated controls treated with saline (0.3 mL ip), 2) sham-operated treated with MitoQ (3.5 mg/kg/day given intraperitoneally in saline), 3) cecal ligation puncture (CLP) mice treated with saline, and 4) CLP mice treated with MitoQ. Forty-eight hours after surgery, we assessed diaphragm force generation, myosin heavy chain content, state 3 mitochondrial oxygen consumption (OCR), and aconitase activity. We also determined effects of MitoQ in female mice with CLP sepsis and in mice with endotoxin-induced sepsis. CLP decreased diaphragm specific force generation and MitoQ prevented these decrements (e.g. maximal force averaged 30.2 ± 1.3, 28.0 ± 1.3, 12.8 ± 1.9, and 30.0 ± 1.0 N/cm2 for sham, sham + MitoQ, CLP, and CLP + MitoQ groups, respectively, P < 0.001). CLP also reduced diaphragm mitochondrial OCR and aconitase activity; MitoQ blocked both effects. Similar responses were observed in female mice and in endotoxin-induced sepsis. Moreover, delayed MitoQ treatment (by 6 h) was as effective as immediate treatment. These data indicate that MitoQ prevents sepsis-induced diaphragm dysfunction, preserving force generation. MitoQ may be a useful therapeutic agent to preserve diaphragm function in critically ill patients with sepsis.NEW & NOTEWORTHY This is the first study to show that Mitoquinone mesylate (MitoQ), a mitochondrially targeted antioxidant, treats sepsis-induced skeletal muscle dysfunction. This biopharmaceutical agent is without known side effects and is currently being used by healthy individuals and in clinical trials in patients with various diseases. When taken together, our results suggest that MitoQ has the potential to be immediately translated into treatment for sepsis-induced skeletal muscle dysfunction.
Mitochondrial rescue prevents glutathione peroxidase-dependent ferroptosis
Free Radic Biol Med2018 Mar;117:45-57.PMID: 29378335DOI: 10.1016/j.freeradbiomed.2018.01.019
Research into oxidative cell death is producing exciting new mechanisms, such as ferroptosis, in the neuropathologies of cerebral ischemia and hemorrhagic brain insults. Ferroptosis is an oxidative form of regulated necrotic cell death featuring glutathione (GSH) depletion, disrupted glutathione peroxidase-4 (GPX4) redox defense and detrimental lipid reactive oxygen species (ROS) formation. Further, our recent findings identified mitochondrial damage in models of oxidative glutamate toxicity, glutathione peroxidase depletion, and ferroptosis. Despite knowledge on the signaling pathways of ferroptosis increasing, the particular role of mitochondrial damage requires more in depth investigation in order to achieve effective treatment options targeting mitochondria. In the present study, we applied RSL3 to induce ferroptosis in neuronal HT22 cells and mouse embryonic fibroblasts. In both cell types, RSL3 mediated concentration-dependent inhibition of GPX4, lipid peroxidation, enhanced mitochondrial fragmentation, loss of mitochondrial membrane potential, and reduced mitochondrial respiration. Ferroptosis inhibitors, such as deferoxamine, ferrostatin-1 and liproxstatin-1, but also CRISPR/Cas9 Bid knockout and the BID inhibitor BI-6c9 protected against RSL3 toxicity. We found compelling new information that the mitochondria-targeted ROS scavenger Mitoquinone (MitoQ) preserved mitochondrial integrity and function, and cell viability despite significant loss of GPX4 expression and associated increases in general lipid peroxidation after exposure to RSL3. Our data demonstrate that rescuing mitochondrial integrity and function through the inhibition of BID or by the mitochondria-targeted ROS scavenger MitoQ serves as a most effective strategy in the prevention of ferroptosis in different cell types. These findings expose mitochondria as promising targets for novel therapeutic intervention strategies in oxidative cell death.
Mitophagy Reduces Oxidative Stress Via Keap1 (Kelch-Like Epichlorohydrin-Associated Protein 1)/Nrf2 (Nuclear Factor-E2-Related Factor 2)/PHB2 (Prohibitin 2) Pathway After Subarachnoid Hemorrhage in Rats
Stroke2019 Apr;50(4):978-988.PMID: 30890112DOI: 10.1161/STROKEAHA.118.021590
Background and Purpose- Mitoquinone has been reported as a mitochondria-targeting antioxidant to promote mitophagy in various chronic diseases. Here, our aim was to study the role of Mitoquinone in mitophagy activation and oxidative stress-induced neuronal death reduction after subarachnoid hemorrhage (SAH) in rats. Methods- Endovascular perforation was used for SAH model of male Sprague-Dawley rats. Exogenous Mitoquinone was injected intraperitoneally 1 hour after SAH. ML385, an inhibitor of Nrf2 (nuclear factor-E2-related factor 2), was given intracerebroventricularly 24 hours before SAH. Small interfering RNA for PHB2 (prohibitin 2) was injected intracerebroventricularly 48 hours before SAH. Nuclear, mitochondrial, and cytoplasmic fractions were gathered using nucleus and mitochondria isolation kits. SAH grade evaluation, short- and long- term neurological function tests, oxidative stress, and apoptosis measurements were performed. Pathway related proteins were investigated with Western blot and immunofluorescence staining. Results- Expression of Keap1 (Kelch-like epichlorohydrin-associated protein 1, 2.84× at 24 hours), Nrf2 (2.78× at 3 hours), and LC3II (light chain 3-II; 1.94× at 24 hours) increased, whereas PHB2 (0.46× at 24 hours) decreased after SAH compared with sham group. Mitoquinone treatment attenuated oxidative stress and neuronal death, both short-term and long-term. Administration of Mitoquinone resulted in a decrease in expression of Keap1 (0.33×), Romo1 (reactive oxygen species modulator 1; 0.24×), Bax (B-cell lymphoma-2 associated X protein; 0.31×), Cleaved Caspase-3 (0.29×) and an increase in Nrf2 (2.13×), Bcl-xl (B-cell lymphoma-extra large; 1.67×), PINK1 (phosphatase and tensin-induced kinase 1; 1.67×), Parkin (1.49×), PHB2 (1.60×), and LC3II (1.67×) proteins compared with SAH+vehicle group. ML385 abolished the treatment effects of Mitoquinone on behavior and protein levels. PHB2 small interfering RNA reversed the outcomes of Mitoquinone administration through reduction in protein expressions downstream of PHB2. Conclusions- Mitoquinone inhibited oxidative stress-related neuronal death by activating mitophagy via Keap1/Nrf2/PHB2 pathway after SAH. Mitoquinone may serve as a potential treatment to relieve brain injury after SAH.