MPP+ Iodide
(Synonyms: 1-甲基-4-苯基吡啶鎓碘化物) 目录号 : GC18188
MPP+ Iodide（1-methyl-4-phenylpyridinium iodide）是神经毒素 MPTP 的一种有毒代谢物，通过选择性破坏黑质中的多巴胺能神经元，在体外模型中成功诱导了帕金森样综合征。
Cas No.:36913-39-0
Sample solution is provided at 25 µL, 10mM.
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Related Biological Data
Nicotine treatment mitigates MPP+- induced apoptosis in HEK293T cells.d The bright field and live/dead staining images of different treatment groups.
Group 1, normal control; group 2, nicotine treatment group; group 3, nicotine + MPP+ treatment group (nicotine was added 4 h before MPP+ treatment); and group 4, MPP+(GlpBio) treatment group. After incubation for 24 h, the cells were washed and incubated with calcein AM and propidium iodide for 30 min.
J Transl Med 22.1 (2024): 1-21. PMID: PMID: 38609979 IF: 7.4001 -
Related Biological Data
Neuroprotective activity of novel natural compounds from marine coral.(C, D) The cell viability of SH-SY5Ycells treated with compounds from the primary screening and MPP+ (500 μM) or H2O2 (100 μM).
SH-SY5Y cell damage models were successfully established by 500 μM MPP+ （Glpbio）or 100 μM H2O2.
CNS Neuroscience & Therapeutics (2022). PMID: 36419251 IF: 7.0348
Quality Control & SDS
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| Cell experiment [1]: | |
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Cell lines |
Bv-2 cells |
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Preparation Method |
The cell experiment took Bv-2 cells as the object, set the MPP+ Iodidefinal concentration of 0.1, 0.2, 0.5 mmol as the interference concentration, and after 24 h of culture, Western blot detected the expression level of NLRP3 protein in cells, and selected the optimal concentration. |
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Reaction Conditions |
0.1, 0.2, 0.5 mmol, 24h |
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Applications |
After 0.1/0.2/0.5 mmol MPP+ Iodide intervention cells for 24 h, MPP+ Iodideactivated cells expressed NLRP3 and MIF protein significantly higher than in the control group. 0.2 mmol MPP+ Iodideis the optimal concentration of NLRP3 inflammasomes that activate Bv-2. |
| Animal experiment [2]: | |
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Animal models |
Male Sprague–Dawley rats |
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Preparation Method |
Four days after siRNA infusion, rats were re-anesthetized for intranigral infusion of MPP+ Iodide(3 µg/µl) at a rate of 0.2 µl/min. After the surgery, rats recovered from anesthesia and were placed in home cages for the indicated times. |
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Dosage form |
3 µg/µl;intranigral infusion |
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Applications |
The results shown intranigral infusion of MPP+ Iodideincreased HO-1 levels in a time-dependent manner; significant HO-1 elevation was observed 24 h to 7 d after MPP+ Iodideinfusion. |
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References: [1]. Huang H, et al. [Macrophage migration inhibitory factor meditates MPP+/MPTP-induced NLRP3 inflammasome activation in microglia cells]. Nan Fang Yi Ke Da Xue Xue Bao. 2021 Jul 20;41(7):972-979. Chinese. [2]. Hung KC, et al. Roles of autophagy in MPP+-induced neurotoxicity in vivo: the involvement of mitochondria and α-synuclein aggregation. PLoS One. 2014 Mar 19;9(3):e91074. |
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MPP+ Iodide (1-methyl-4-phenylpyridinium?iodide) is a toxic metabolite of the neurotoxin MPTP, and has successfully induced Parkinson-like syndromes in an in vitro model by selectively destroying dopaminergic neurons in substantia nigra.[1]
In vitro efficacy test it shown that when SH-SY5Y cells were exposed to MPP+ Iodidein the range of 1–100 M for 3–24 h, MPP+ Iodide exhibited a dose-time dependent cytotoxicity.[1] In vitro experiment it indicated that SH-SY5Y cells were treated with 0.2, 0.4, 0.8, or 1.0 mM MPP?+ for 24 h, MPP+ Iodide?could significantly reduce cell viability in a dose-dependent manner.[2] In vitro, treatment with 1-7.5 mM of MPP+ Iodide dose-dependently increased the neurodegeneration in the L1 larvae of BZ555 worms. The percentages of worms exhibiting neurodegeneration after treatment with 1 mM, 2.5 mM, 5 mM and 7.5 mM MPP+ Iodide were 24%, 27%, 67% and 87%, respectively.[3] Both TSM1 and primary neurons were treated with 0.1 to 2 mM of MPP+ Iodide induced neuronal cell death in a concentration dependent manner in vitro. TSM1 cells and primary neurons were treated with 400 μM MPP+ Iodide decreased by 60% and 80% the cell viability as compared to the control, respectively.[4] In vitro to test the role of MAC1 in MPTP/MPP+-induced neurotoxicity, neuron-glia cultures were treated with 0.125, 0.25, or 0.5 μM of MPP+ Iodidefound that MPP+-induced DAergic neurotoxicity in neuron-glia cultures was attenuated in the absence of MAC1.[5]
In vivo study indicated that intranigral infusion of 3 μg/μl MPP+ Iodideinduced oxidative injury in nigrostriatal dopaminergic system of rat brain; and autophagy is pro-death in the MPP+-induced oxidative injury.[6]
References:
[1].Reudhabibadh R, et al. Suppressing Cdk5 Activity by Luteolin Inhibits MPP+-Induced Apoptotic of Neuroblastoma through Erk/Drp1 and Fak/Akt/GSK3β Pathways. Molecules. 2021 Feb 28;26(5):1307.
[2].Yan J, et al. Artemisinin attenuated oxidative stress and apoptosis by inhibiting autophagy in MPP+-treated SH-SY5Y cells. J Biol Res (Thessalon). 2021 Feb 25;28(1):6.
[3].Anjaneyulu J, et al. Differential effect of Ayurvedic nootropics on C.?elegans models of Parkinson's disease. J Ayurveda Integr Med. 2020 Oct-Dec;11(4):440-447.
[4].Petit-Paitel A, et al. Involvment of cytosolic and mitochondrial GSK-3beta in mitochondrial dysfunction and neuronal cell death of MPTP/MPP-treated neurons. PLoS One. 2009;4(5):e5491.
[5].Hu X, et al. Macrophage antigen complex-1 mediates reactive microgliosis and progressive dopaminergic neurodegeneration in the MPTP model of Parkinson's disease. J Immunol. 2008 Nov 15;181(10):7194-204.
[6].Hung KC, et al. Roles of autophagy in MPP+-induced neurotoxicity in vivo: the involvement of mitochondria and α-synuclein aggregation. PLoS One. 2014 Mar 19;9(3):e91074.
MPP+ Iodide（1-methyl-4-phenylpyridinium iodide）是神经毒素 MPTP 的一种有毒代谢物，通过选择性破坏黑质中的多巴胺能神经元，在体外模型中成功诱导了帕金森样综合征。[ 1]
体外药效试验表明，当 SH-SY5Y 细胞暴露于 1-100 M 范围内的 MPP+ 碘化物 3-24 小时时，MPP+ 碘化物表现出剂量时间依赖性细胞毒性。[1]< /sup> 体外实验表明，SH-SY5Y 细胞用 0.2、0.4、0.8 或 1.0 mM MPP + 处理 24 h，MPP+ Iodide〉 可以剂量依赖性方式显着降低细胞活力。[2 ] 在体外，用 1-7.5 mM 的 MPP+ 碘化物处理会剂量依赖性地增加 BZ555 蠕虫 L1 幼虫的神经变性。用 1 mM、2.5 mM、5 mM 和 7.5 mM MPP+ 碘化物处理后表现出神经变性的蠕虫百分比分别为 24%、27%、67% 和 87%。[3] TSM1 和用 0.1 至 2 mM 的 MPP+ 碘化物处理初级神经元，在体外以浓度依赖性方式诱导神经元细胞死亡。 TSM1 细胞和原代神经元用 400 μM MPP+ 碘化物处理，与对照相比，细胞活力分别降低了 60% 和 80%。[4] 在体外测试 MAC1 在 MPTP 中的作用/MPP+- 诱导的神经毒性，神经胶质培养物用 0.125、0.25 或 0.5 μM 的 MPP+ 碘化物处理，发现在没有 MAC1 的情况下，MPP+- 诱导的神经胶质培养物中的 DAergic 神经毒性减弱。[5]/ p>\n
体内研究表明，黑质内输注 3 μg/μl MPP+ 碘化物可诱导大鼠大脑黑质纹状体多巴胺能系统的氧化损伤；在 MPP+- 诱导的氧化损伤中，自噬促进死亡。[6]
| Cas No. | 36913-39-0 | SDF | |
| 别名 | 1-甲基-4-苯基吡啶鎓碘化物 | ||
| 化学名 | 1-methyl-4-phenyl-pyridinium, monoiodide | ||
| Canonical SMILES | C[N+](C=C1)=CC=C1C2=CC=CC=C2.[I-] | ||
| 分子式 | C12H12N.I | 分子量 | 297.1 |
| 溶解度 | 100 mM in Water | 储存条件 | Store at RT |
| 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 | 3.3659 mL | 16.8294 mL | 33.6587 mL |
| 5 mM | 0.6732 mL | 3.3659 mL | 6.7317 mL |
| 10 mM | 0.3366 mL | 1.6829 mL | 3.3659 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。
Mitochondrial dysfunction and apoptosis are attenuated through activation of AMPK/GSK-3β/PP2A pathway in Parkinson's disease
Eur J Pharmacol.2021 Sep 15;907:174202.PMID:34048739DOI: 10.1016/j.ejphar.2021.174202.
Parkinson's disease (PD) is a common neurological disorder worldwide, characterized by loss of dopaminergic neurons and decrease of dopamine content. Mitochondria plays an important role in the development of PD. Adenosine 5'-monophosphate-activated protein kinase (AMPK), glycogen synthase kinase 3 (GSK-3β) and protein phosphatase 2A (PP2A) are all key proteins that regulate mitochondrial metabolism and apoptosis, and they are involved in a variety of neurodegenerative diseases. Here, we aimed to explore the involvement of mitochondrial dysfunction and apoptosis in 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine hydrochloride (MPTP)-induced PD mice and MPP+ iodide-induced PC12 cells. MPTP-induced mice were subjected to behavioral testing to assess PD-like behaviors. Various molecular biological techniques including ELISA, Western blot, TUNEL assay, flow cytometry, and the important instruments Seahorse XF24 Extracellular and high performance liquid chromatography (HPLC), were used to identify the underlying molecular events of mitochondria. Treatment with the AMPK activator GSK621 dramatically ameliorated PD by increasing the levels of dopamine and rescuing the loss of dopaminergic neurons, which is dependent on the mitochondrial pathway. Moreover, regulation of AMPK/GSK-3β/PP2A pathway-related proteins by GSK621 was partially inhibited the development of PD, suggesting a negative feedback loop exists between AMPK action and mitochondrial dysfunction-mediated apoptosis. Our data preliminarily indicated that mitochondrial dysfunction and apoptosis in the pathogenesis of PD might be mediated by AMPK/GSK-3β/PP2A pathway action, which might be a promising new option for future therapy of PD.
Neuroprotective actions of deferiprone in cultured cortical neurones and SHSY-5Y cells
J Neurochem.2008 Jun 1;105(6):2466-76.PMID:18331585DOI: 10.1111/j.1471-4159.2008.05332.x.
Alzheimer's disease (AD) is a common neurodegenerative disorder, but the initiating molecular processes contributing to neuronal death are not well understood. AD is associated with elevated soluble and aggregated forms of amyloid beta (Abeta) and with oxidative stress. Furthermore, there is increasing evidence for a detrimental role of iron in the pathogenic process. In this context, iron chelation by compounds such as 3-hydroxypyridin-4-one, deferiprone (Ferriprox) may have potential neuroprotective effects. We have evaluated the possible neuroprotective actions of deferiprone against a range of AD-relevant insults including ferric iron, H(2)O(2) and Abeta in primary mouse cortical neurones. We have investigated the possible neuroprotective actions of deferiprone (1, 3, 10, 30 or 100 microM) in primary neuronal cultures following exposure to ferric iron [ferric nitrilotriacetate (FeNTA); 3 and 10 microM], H(2)O(2) (100 microM) or Abeta1-40 (3, 10 and 20 microM). Cultures were treated with deferiprone or vehicle either immediately or up to 6 h after the insult in a 24-well plate format. In order to elucidate a possible neuroprotective action of deferiprone against Parkinson's disease relevant insults another group of experiments were performed in the human neuroblastoma catecholaminergic SHSY-5Y cell line. SHSY-5Y cells were treated with MPP(+) iodide, the active metabolite of the dopaminergic neurotoxin MPTP and the neuroprotective actions of deferiprone evaluated. Cytotoxicity was assessed at 24 h by lactate dehydrogenase release, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium-bromide turnover (FeNTA and hydrogen peroxide) and morphometric analysis of cell viability by Hoechst 33324/propidium iodide (FeNTA, Abeta and MPP(+)) or 6-carboxyfluorescein diacetate and annexin V-Cy3 (Abeta). The present study demonstrates that deferiprone protects against FeNTA, hydrogen peroxide, MPP(+) and Abeta1-40-induced neuronal cell death in vitro, which is consistent with previous in vitro and in vivo studies that have demonstrated similar protection with other iron chelators.
Differential effect of Ayurvedic nootropics on C. elegans models of Parkinson's disease
J Ayurveda Integr Med.2020 Oct-Dec;11(4):440-447.PMID:32978047DOI: 10.1016/j.jaim.2020.07.006.
Background: Globally, there is increased incidence of Parkinson's Disease (PD), which is the second most common age-related neurodegenerative disease. The currently available PD-therapeutics provide only symptomatic relief. Thus, there is an urgent need to devise an effective and safe treatment strategy for PD. The holistic approach of Ayurveda can be a potential effective strategy for treating PD. The integration of different medicine systems, such as modern bio-medicine and Ayurveda can be an effective strategy for treatment of complex diseases, including PD. Objective: This study aimed to evaluate the neuroprotective mechanism of six Ayurvedic nootropics that are commonly used to treat PD. Material and methods: Six Ayurvedic herbs, namely Mucuna pruriens (MP), Bacopa monnieri (BM), Withania somnifera (WS), Centella asiatica (CA), Sida cordifolia (SC), and Celastrus paniculatus (CP), were selected after consultation with Ayurvedic scholars and physicians. The mode of action of methanolic herbal extracts was evaluated using the Caenorhabditis elegans BZ555 and NL5901 strains, which can be used to model the two main hallmarks of PD, namely degeneration of dopaminergic neurons and aggregation of α-synuclein protein. Results: All six herbal extracts exhibited neuroprotective effect. The extracts of BM and MP exhibited maximum protection against 1-methyl-4-phenylpyridinium iodide (MPP+ iodide)-induced dopaminergic neurodegeneration in the BZ555 strain. Furthermore, the herbal extracts, except CA extract, inhibited the aggregation of heterologously expressed human α-synuclein in the NL5901 strain. Conclusion: Ayurvedic herbs used in the treatment of PD exhibited differential neuroprotective and protein aggregation mitigating effects in C. elegans.
UNC-51-like kinase 1 blocks S6k1 phosphorylation contributes to neurodegeneration in Parkinson's disease model in vitro
Biochem Biophys Res Commun.2015 Apr 3;459(2):196-200.PMID:25680463DOI: 10.1016/j.bbrc.2015.02.008.
Objective: This study was aim to determine the role and underling mechanism of ribosomal protein S6 kinases 1 (S6k1) phosphorylation in Parkinson's disease (PD). Methods: The dopaminergic neuron MN9D was employed and 1-methyl-4-phenylpyridium (MPP) iodide (MPP(+)) was used to generate PD model in vitro. The S6k1 phosphorylation and UNC-51-like kinase 1 (ULK1) protein levels were analyzed by western blot. The ULK1 mRNA level was evaluated by Real-time RT-PCR. The S6k1 threonine 389 (T389) site-directed mutagenesis, the phosphodeficit T389A (threonine to alanine) and the phosphomimetic T389D (threonine to aspartate) were generated to examine the phosphorylation site of S6k1. Results: An increase in the ULK1 mRNA and protein levels were detected in the MPP(+)-treated MN9D cells compared to control. ULK1 knockdown increased neuronal cell viability, and enhanced S6k1 phosphorylation. Further investigation demonstrated ULK1 knockdown promoted the S6k1 T389 phosphorylation in particular. T389A enhanced the viability of MPP iodide-treated MN9D, whereas T389D decreased the cell viability. Conclusion: ULK1 acts to inhibit S6k1 phosphorylation at T389, leading to MN9D viability reduction under MPP(+) treatment. These results provide evidence for a novel mechanism by which the ULK1 inhibit S6k1 T389 phosphorylation contributes to neurodegeneration in MPP(+) treated-MN9D, and suggests a new therapeutic strategy for PD.