Background
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]
参考文献:
[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]
Protocol
| Cell experiment [1]: |
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Cell lines
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Bv-2 cells
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Preparation Method
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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
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0.1, 0.2, 0.5 mmol, 24h
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Applications
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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.
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| Animal experiment [2]: |
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Animal models
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Male Sprague–Dawley rats
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Preparation Method
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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
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3 μg/μl;intranigral infusion
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Applications
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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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参考文献:
[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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