异吲哚啉二酮的新合成衍生物:合成、神经保护试验以及对神经元样细胞系中氧化应激相关基因表达水平的影响。

IF 2.6 4区 生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY Journal of Receptors and Signal Transduction Pub Date : 2023-12-01 Epub Date: 2024-02-13 DOI:10.1080/10799893.2023.2291559
Abdolrahim Pourparizi, Mina Vazirinia, Fatemeh Pourrajab, Hamid Nadri, Asghar Davood
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引用次数: 0

摘要

目的:氧化应激会损伤细胞并导致与年龄有关的疾病,如阿尔茨海默氏症、帕金森氏症和亨廷顿氏症。本研究考察了新合成的异吲哚衍生物及其通过 NRF2 信号通路对处于氧化应激下的 SH-SY5Y 神经母细胞瘤细胞的影响。NRF2 转录因子在氧化应激反应和细胞稳态中发挥着重要作用:方法:通过邻苯二甲酸酐与 4-(2-氨基乙基)-1-苄基哌啶反应合成了三种异吲哚啉二酮衍生物。它们的结构通过傅立叶变换红外光谱、核磁共振和质谱进行了确认。然后,在过氧化氢(H2O2)诱导的氧化应激模型下,在人 SH-SY5Y 细胞上测试了这些衍生物。24 小时后,对细胞活力、ROS 水平、蛋白质羰基含量以及 NRF2 和第二阶段抗氧化酶的基因表达进行了测定:结果:观察到三种异吲哚啉衍生物(3a-3c)通过保护细胞免受氧化应激、减少细胞内活性氧和羰基化蛋白、增加 NRF2 和相关基因(如 NQO-1 和 GSTK1)的基因表达水平来提高 SH-SY5Y 细胞的活力:结论:异吲哚啉衍生物通过多种神经保护机制对 SH-SY5Y 细胞具有神经保护作用,但还需要更多的研究。
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New synthetic derivatives of isoindoline-dione: synthesis, neuroprotection assay and impact on the expression level of oxidative stress-related genes in neuronal-like cell line.

Purpose: Oxidative stress can damage cells and cause age-related illnesses such as Alzheimer's, Parkinson's, and Huntington's. This study looked at newly synthesized isoindole derivatives and their effects on SH-SY5Y as a neuroblastoma cell under oxidative stress through the NRF2 signaling pathway. NRF2 transcription factor plays a vital role in the oxidative stress response and cellular homeostasis.

Method: Three isoindoline-dione derivatives were synthesized by reacting phthalic anhydrides with 4-(2-aminoethyl)-1-benzyl piperidine. Their structures were confirmed through FT-IR, NMR, and Mass spectroscopy. The derivatives were then tested on human SH-SY5Y cells under an oxidative stress model induced by hydrogen peroxide (H2O2). The cell viability, ROS levels, protein carbonyl content, and gene expression of NRF2 and phase II antioxidative enzymes were measured after 24 h.

Results: Three isoindoline derivatives (3a-3c) were observed to increase the viability of SH-SY5Y cells by protective against oxidative stress, reducing intracellular reactive oxygen species and carbonylated proteins, and increasing gene expression levels of NRF2 and associated genes such as NQO-1, and GSTK1.

Conclusion: Isoindoline derivatives demonstrated a neuroprotective effect on SH-SY5Y cells through various neuroprotective mechanisms, although more studies are needed.

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来源期刊
Journal of Receptors and Signal Transduction
Journal of Receptors and Signal Transduction 生物-生化与分子生物学
CiteScore
6.60
自引率
0.00%
发文量
19
审稿时长
>12 weeks
期刊介绍: Journal of Receptors and Signal Tranduction is included in the following abstracting and indexing services: BIOBASE; Biochemistry and Biophysics Citation Index; Biological Abstracts; BIOSIS Full Coverage Shared; BIOSIS Previews; Biotechnology Abstracts; Current Contents/Life Sciences; Derwent Chimera; Derwent Drug File; EMBASE; EMBIOLOGY; Journal Citation Reports/ Science Edition; PubMed/MedLine; Science Citation Index; SciSearch; SCOPUS; SIIC.
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