N-acetylserotonin Derivative Exerts a Neuroprotective Effect by Inhibiting the NLRP3 Inflammasome and Activating the PI3
- PDF / 8,790,818 Bytes
- 12 Pages / 595.276 x 790.866 pts Page_size
- 98 Downloads / 197 Views
ORIGINAL PAPER
N-acetylserotonin Derivative Exerts a Neuroprotective Effect by Inhibiting the NLRP3 Inflammasome and Activating the PI3K/Akt/ Nrf2 Pathway in the Model of Hypoxic-Ischemic Brain Damage Xing Luo1,2 · Honglan Zeng1 · Chengzhi Fang1 · Bing‑Hong Zhang1 Received: 25 March 2020 / Revised: 31 August 2020 / Accepted: 7 November 2020 © Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract Neonatal hypoxic-ischemic encephalopathy (HIE) is one of the main causes of neonatal disability and death. As a derivative of N-acetylserotonin, N-[2-(5-hydroxy-1H-indol-3-yl) ethyl]-2-oxopiperidine-3-carboxamide (HIOC) can easily cross the blood–brain barrier and have a long half-life in the brain. In this study, the hypothesis was verified that HIOC plays a neuroprotective role in the HIE model and its potential mechanism was evaluated. Firstly, an HIE rat model was established to deliver HIOC, revealing that it can reduce cerebral infarction volume, cerebral edema, and neuronal apoptosis. The results of immunofluorescence staining, Western blots and RT-PCR further showed that HIOC could inhibit the activation of the NLRP3 inflammasome and the expression of related proteins. Finally, the activation of the phosphatidylinositol-3-kinase (PI3K)/Akt/nuclear factor erythroid 2-related factor 2 (Nrf2) pathway by HIOC was verified in vitro and in vivo. It was discovered that HIOC could increase the nuclear translocation of Nrf2, and that this induction can be reversed by the PI3K/Akt pathway inhibitor LY294002. In general terms, the neuroprotective effect of HIOC was confirmed in the HIE model, which is related to the activation of the Pi3k/Akt/Nrf2 signal pathway and the inhibition of the NLRP3 inflammasome. Keywords N-[2-(5-hydroxy-1H-indol-3-yl) ethyl]-2-oxopiperidine-3-carboxamide · Hypoxic-ischemic encephalopathy · NLRP3 inflammasome · Nrf2 Abbreviations Akt Protein kinase B DAPI 4′,6-diamidino-2-phenylindole HIE Hypoxic-ischemic encephalopathy HIOC N-[2-(5-hydroxy-1H-indol-3-yl) ethyl]-2-oxopiperidine-3-carboxamide HO-1 Heme oxygenase-1 Electronic supplementary material The online version of this article (doi:https://doi.org/10.1007/s11064-020-03169-x) contains supplementary material, which is available to authorized users. * Chengzhi Fang [email protected] * Bing‑Hong Zhang [email protected] 1
Departments of Neonatology, Renmin Hospital of Wuhan University, Ziyang Road Wuchang District, No. 99 Jiefang Road, Wuhan 430060, Hubei Province, China
Central Laboratory, Renmin Hospital of Wuhan University, Wuhan, Hubei Province, China
2
Iba-1 Ionized calcium binding adapter molecule 1 IL Interleukin NAS N-acetylserotonin Nrf2 Nuclear factor erythroid 2-related factor 2 PI3K Phosphatidylinositol 3-kinase TNF-α Tumor necrosis factor-α TTC 2, 3, 5-triphenyltetrazolium chloride TUNEL Terminal deoxynucleotidyl transferase dUTP nick end labeling
Introduction Hypoxic-ischemic encephalopathy (HIE) is a common complication which often follows perinatal asphyxia, and can cause neurologi
Data Loading...
