白桦酸通过p38MAPK/NF-κB/GPX4/Nrf2/Keap-1/HO-1信号轴保护暴露于脂多糖和硫酸亚铁的SH-SY5Y细胞。

IF 2.9 3区 生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY
Shivam Kumar Pandey, Hardev Singh, Shad Ahmad, Rakesh Kumar Singh
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引用次数: 0

摘要

白桦酸(BA)是一种五环三萜化合物,具有广泛的药理潜力,并因其神经保护作用而得到广泛认可。本研究探讨该化合物对体外分化的人神经母细胞瘤SH-SY5Y细胞抗LPS和feso4诱导的铁凋亡、细胞凋亡、神经炎症和多巴胺能细胞死亡的潜在保护作用,并探讨其机制。将分化的人神经母细胞瘤SH-SY5Y细胞暴露于LPS和FeSO4中,采用MTT法评估细胞活力。流式细胞术观察凋亡细胞的死亡情况。此外,通过western blotting和免疫细胞化学染色技术分析与铁下垂、凋亡相关的关键标志物和其他相关信号蛋白的表达水平。然而,LPS和FeSO4共同暴露会导致细胞活力的剂量依赖性降低,而BA预处理(0.3-30μM)可显著逆转这一趋势。LPS和FeSO4使DMT1、Bax、caspase-3和α -突触核蛋白水平升高,GPX4、FTH1、SLC7A11、Nrf2、Keap1、HO-1、PARK7、Bcl-2、NeuN和TH水平降低,导致细胞铁凋亡、凋亡和多巴胺能细胞死亡。此外,LPS和FeSO4显著增加了细胞中IL-6、TNF-α的表达以及p38、pMAPK和pNFkB的磷酸化。BA预处理显著抑制LPS和feso4诱导的促炎细胞因子、铁下垂、细胞凋亡和多巴胺能细胞死亡标志物的上调。这些发现表明BA通过调节GPX4/Nrf2/Keap-1/HO-1抗氧化防御和p38MAPK/NF-κB炎症信号通路发挥神经保护作用,突出了其作为氧化应激相关神经退行性疾病(如帕金森病)的治疗药物的潜力。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Betulinic acid protects sH-SY5Y cells exposed to lipopolysaccharide and ferrous sulfate through p38MAPK/NF-κB/GPX4/Nrf2/keap-1/HO-1 signaling axis.

Betulinic acid (BA) is a pentacyclic triterpenoid with broad pharmacological potential and widely recognized for its neuroprotective effects. This study investigated the potential protective effects of this compound on in vitro differentiated human neuroblastoma SH-SY5Y cells against LPS and FeSO4-induced ferroptosis, apoptosis, neuroinflammation, and dopaminergic cell death, and explored the underlying mechanisms. Differentiated human neuroblastoma SH-SY5Y cells were exposed to LPS and FeSO4, and the cellular viability was evaluated using the MTT assay. Flow cytometry was performed to assess apoptotic cell death. Additionally, the expression levels of key markers associated with ferroptosis, apoptosis, and other relevant signaling proteins were analyzed through western blotting and Immunocytochemical staining techniques. However, co-exposure with LPS and FeSO4 resulted in a dose-dependent reduction in cell viability, which was significantly reversed by pretreatment with BA (0.3-30μM). Exposure to LPS and FeSO4 increased the DMT1, Bax, caspase-3, and alpha-synuclein, and decreased the GPX4, FTH1, SLC7A11, Nrf2, Keap1, HO-1, PARK7, Bcl-2, NeuN, and TH levels, resulting in cell ferroptosis, apoptosis, and dopaminergic cell death. Furthermore, LPS and FeSO4 significantly increased the expression of IL-6, TNF-α, and phosphorylation of p38, pMAPK, and pNFkB in the cells. Pretreatment with BA markedly suppressed LPS and FeSO4-induced upregulation of pro-inflammatory cytokines, ferroptosis, apoptosis, and dopaminergic cell death markers. These findings suggest that BA exerts neuroprotection by modulating the GPX4/Nrf2/Keap-1/HO-1 antioxidant defense and p38MAPK/NF-κB inflammatory signaling pathways, highlighting its potential as a therapeutic agent for oxidative stress-related neurodegenerative conditions, such as Parkinson's disease (PD).

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来源期刊
Free Radical Research
Free Radical Research 生物-生化与分子生物学
CiteScore
6.70
自引率
0.00%
发文量
47
审稿时长
3 months
期刊介绍: Free Radical Research publishes high-quality research papers, hypotheses and reviews in free radicals and other reactive species in biological, clinical, environmental and other systems; redox signalling; antioxidants, including diet-derived antioxidants and other relevant aspects of human nutrition; and oxidative damage, mechanisms and measurement.
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