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A Guide to Production, Crystallization, and Structure Determination of Human IKK1/α
Published on: November 2, 2018
Brazilin-Ce nanoparticles attenuate inflammation by de/anti-phosphorylation of IKKβ
Shengxuan Li1, Kun Wang2, Kai Jiang1
1State Key Laboratory of Cardiology, Shanghai East Hospital, School of Life Sciences and Technology, Tongji University, Shanghai, 200092, China.
Abstract:
Inflammation is associated with a series of diseases like cancer, cardiovascular disease and infection, and phosphorylation/dephosphorylation modification of proteins are important in inflammation regulation. Here we designed and synthesized a novel Brazilin-Ce nanoparticle (BX-Ce NPs) using Brazilin, which has been used for anti-inflammation in cardiovascular diseases but with narrow therapeutic window, and Cerium (IV), a lanthanide which has the general activity in catalyzing the hydrolysis of phosphoester bonds, to conferring de/anti-phosphorylation of IKKβ. We found that BX-Ce NPs specifically bound to Asn225 and Lys428 of IKKβ and inhibited its phosphorylation at Ser181, contributing to appreciably anti-inflammatory effect in cellulo (IC50 = 2.5 μM). In vivo mouse models of myocardial infarction and sepsis also showed that the BX-Ce NPs significantly ameliorated myocardial injury and improved survival in mice with experimental sepsis through downregulating phosphorylation of IKKβ. These findings provided insights for developing metal nanoparticles for guided ion interfere therapy, particularly synergistically target de/anti-phosphorylation as promising therapeutic agents for inflammation and related diseases.
Insights
Novel Brazilin-Cerium nanoparticles (BX-Ce NPs) effectively reduce inflammation by inhibiting IKKβ phosphorylation. These nanoparticles show promise for treating inflammatory diseases like cardiovascular conditions and sepsis.
Area of Science:
- Biomedical Engineering
- Nanotechnology
- Inflammation Research
Background:
- Protein phosphorylation/dephosphorylation is crucial in regulating inflammation.
- Brazilin offers anti-inflammatory benefits but has a narrow therapeutic window.
- Cerium (IV) nanoparticles can catalyze phosphoester bond hydrolysis.
Purpose of the Study:
- To design and synthesize novel Brazilin-Cerium nanoparticles (BX-Ce NPs).
- To investigate the anti-inflammatory effects of BX-Ce NPs by targeting IKKβ phosphorylation.
- To evaluate the therapeutic potential of BX-Ce NPs in vivo models.
Main Methods:
- Synthesis of Brazilin-Cerium nanoparticles (BX-Ce NPs).
- In vitro assays to determine binding sites and inhibition of IKKβ phosphorylation.
- In vivo studies using mouse models of myocardial infarction and sepsis.
Main Results:
- BX-Ce NPs specifically bind to Asn225 and Lys428 of IKKβ, inhibiting its phosphorylation at Ser181 (IC50 = 2.5 μM).
- BX-Ce NPs demonstrated significant anti-inflammatory effects in vitro.
- In vivo studies showed amelioration of myocardial injury and improved survival in sepsis models.
Conclusions:
- BX-Ce NPs exhibit potent anti-inflammatory activity by downregulating IKKβ phosphorylation.
- These nanoparticles offer a promising therapeutic strategy for inflammation-related diseases.
- BX-Ce NPs represent a novel approach for guided ion interference therapy targeting de/anti-phosphorylation.
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