NEUROTOXICOLOGY
·
2021
·
IF 4.294
Qingxin Song,Shanxin Peng,Xiaosong Zhu
Baicalein, a major bioactive flavone constituent isolated from Scutellaria baicalensis Georgi, has neuroprotective properties in several neurological disorders. Many studies suggest that oxidative stress plays a central role in the pathogenesis of Parkinson’s disease (PD). Baicalein has also been shown to have antioxidant effects. Therefore, the current study was designed to investigate whether baicalein could protect against MPP + /MPTP-induced neurotoxicity via suppressing oxidative stress in vitro and in vivo . In vitro , our results showed that baicalein increased cell viability in MPP + -treated SH-SY5Y cells. Treatment with baicalein could reversed the increased MDA and ROS levels, and the decreased GSH levels in MPP + -treated SH-SY5Y cells. In MPTP-treated mice, baicalein ameliorated MPTP-induced motor impairment and suppressed the MPTP-induced accumulation of iron and lipid peroxides. Besides, baicalein improved the neurotoxicity induced by MPTP as seen by a significant raise of tyrosine hydroxylase (TH) and simultaneous decrease of monoamine-oxidase-B (MAO-B). The inhibitory effect of baicalein on oxidative stress probably was partially governed by inhibition of ERK activation. In conclusion, our results suggest that baicalein could prevent MPP+/MPTP-induced neurotoxicity via suppressing oxidative stress.
研究领域:
神经科学
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药理学
·
分子生物学
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DOI
PubMed
高影响因子
TOXICOLOGY LETTERS
·
2018
·
IF 3.166
Lin Li,Jiahui Cui,Zi Liu,Xuejiao Zhou,Zengqiang Li,Yang Yu,Yuanyuan Jia,Daiying Zuo,Yingliang Wu
Silver nanoparticles (AgNPs) have many medical and commercial applications, but their effects on human health are poorly understood. The aim of this study was to assess the effect of AgNPs on the human neuroblastoma cell line SH-SY5Y and to explore their potential mechanisms of action. We found that AgNPs decreased SH-SY5Y cell viability in a dose- and time-dependent manner. Exposure to AgNPs activated endoplasmic reticulum (ER) stress, as reflected by upregulated expression of glucose-regulated protein 78 (GRP78), phosphorylated PKR-like endoplasmic reticulum kinase (p-PERK), phosphorylated eukaryotic translation initiation factor 2α (p-eIF2α), C/EBP homology protein (CHOP), spliced X-box binding protein-1 (XBP1), and phosphorylated inositol-requiring enzyme (p-IRE), all of which are involved in the cellular unfolded protein response. Prolonged exposure of cells to AgNPs damaged calcium (Ca 2+ ) homeostasis, increased the length of contact sites between the ER and mitochondria, altered IP 3 R function by the increased levels of phosphatase and tensin homolog deleted on chromosome ten (PTEN) in the ER and enhanced mitochondrial Ca 2+ uptake. Finally, Ca 2+ overload and disrupted homeostasis in the mitochondria triggered apoptotic cell death. Our results suggest that caution should be exercised in the use of AgNPs in humans.
研究领域:
纳米技术
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细胞生物学
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毒理学
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神经科学
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DOI
PubMed
高影响因子
TOXICOLOGY
·
2021
·
IF 4.221
Shuangyu Guo,Bo Zhang,Wen Qi,Xiaolian Cao,Yixuan Xu,Xueting Zhang,Xu Li,Liting Zhou,Lin Ye
Estrogen receptors are involved in regulating the proliferation and invasion process of neuroblastoma . As a kind of estrogen-like environmental endocrine disruptors (EEDs), whether mono-2-ethylhexyl phthalate (MEHP) can affect the proliferation and invasion of neuroblastoma cells via ERs is unknown. The present study aimed to explore the role of ERα in MEHP-induced proliferation, migration, and invasion of SH-SY5Y cells. SH-SY5Y cells were cultured in DMEM with 10 % FBS. Wild-type SH-SY5Y cells and ERα-knockdown SH-SY5Y cells were treated with MEHP (0, 10, 50, and 250 μM) for 12 h and 24 h. The viability of SH-SY5Y cells was detected with a CCK8 kit and cell cycle was measured by flow cytometry. Cell migration was measured using a scratch assay, and cell invasion was tested using a Transwell migration assay. The expression levels of proliferating cell nuclear antigen (PCNA), matrix metalloproteinase 2 (MMP-2), matrix metalloproteinase 9 (MMP-9), tissue inhibitor of matrix metalloproteinase 2 (TIMP-2), ERα, and ERβ were detected with real-time qPCR and western blotting . MEHP promoted the proliferation of SH-SY5Y cells. The results also showed that MEHP significantly increased the relative migration distance of wild-type SH-SY5Y cells. Conversely, MEHP treatment did not increase the relative migration distance of ERα-knockdown SH-SY5Y cells, suggesting that MEHP promotes the migration of neuroblastoma through ERα. Similarly, MEHP significantly increased the relative number of invaded wild-type SH-SY5Y cells, while the MEHP-induced invasion effect was significantly decreased in ERα-knockdown SH-SY5Y cells. Moreover, the expression levels of PCNA, MMP-2, MMP-9, and ERα cells were upregulated by MEHP in wild-type SH-SY5Y, and the expression level of its tissue inhibitor TIMP-2 was downregulated. In contrast, the expression of PCNA, MMP-2, MMP-9, and ERα was significantly downregulated in ERα-knockdown SH-SY5Y cells, while the expression of TIMP-2 was significantly upregulated. In conclusion, MEHP can upregulate PCNA, MMP-2, and MMP-9, and downregulate TIMP-2, further promoting proliferation, migration, and invasion of neuroblastoma through ERα.
研究领域:
癌症生物学
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毒理学
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细胞生物学
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DOI
PubMed
高影响因子
NEUROCHEMICAL RESEARCH
·
2016
·Vol. 41
·期 9
·2311-2323
·
IF 2.472
Liu Jie,Su Hua,Qu Qiu-Min
Beta-amyloid (Aβ), the hallmark protein in Alzheimer’s disease (AD), induces neurotoxicity that involves oxidative stress and mitochondrial dysfunction, leading to cell death. Carnosic acid (CA), a polyphenolic diterpene isolated from the herb rosemary ( Rosemarinus officinalis ), was investigated in our study to assess its neuroprotective effect and underlying mechanism against Aβ-induced injury in human neuroblastoma SH-SY5Y cells. We found that CA pretreatment alleviated the Aβ 25–35 -induced loss of cell viability, inhibited both Aβ 1–42 accumulation and tau hyperphosphorylation, reduced reactive oxygen species generation, and maintained the mitochondrial membrane potential. Moreover, CA increased the microtubule-associated protein light chain 3 (LC3)-II/I ratio and decreased SQSTM1(p62), indicating that CA could induce autophagy. Autophagy inhibitor 3-methyladenine (3-MA) attenuated the neuroprotective effect of CA, suggesting that autophagy was involved in the neuroprotection of CA. It was also observed that CA activated AMP-activated protein kinase (AMPK) but inhibited mammalian target of rapamycin (mTOR). Furthermore, blocking AMPK with si-AMPKα successfully inhibited the upregulation of LC3-II/I, prevented the downregulation of phosphorylation of mTOR and SQSTM1(p62), indicating that CA induced autophagy in SH-SY5Y cells via the activation of AMPK. These results suggested that CA might be a potential agent for preventing AD.
研究领域:
神经科学
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药理学
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细胞生物学
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DOI
PubMed
高影响因子
MOLECULAR AND CELLULAR BIOCHEMISTRY
·
2024
·
IF 3.5
Wang Liwei,Zhang Lu,Yun Yang,Liang Tingting,Yan Chaoqun,Mao Zhuoya,Zhang Jingfang,Liu Baoshe,Zhang Jian,Liang Taigang
Occupational and unintentional exposure of zinc oxide nanoparticles (ZnONPs) raises concerns regarding their neurotoxic potential and there is an urgent need for the development of effective agents to protect against the toxic effects of ZnONPs. Astragalus memeranaceus (AM), a famous Traditional Chinese Medicine, as well as its bioactive components, showing a potential neuroprotective function. This study aims to investigate the neuroprotective effects of bioactive components of AM against ZnONPs-induced toxicity in human neuroblastoma SH-SY5Y cells and its underlying mechanisms. The cell apoptosis, ROS generation, MMP changes, mitochondrial fission/fusion, biogenesis, and mitophagy were assessed. In this study, AM treatment inhibited ZnONPs-induced cell apoptosis and ROS overproduction in SH-SY5Y cells. And astragaloside IV (ASIV) played a dominant role in the attenuation of cytotoxicity after ZnONPs exposure, rather than flavonoids and polysaccharides. ASIV treatment significantly reduced ROS generation and MMP collapse in ZnONPs-exposed cells. Furthermore, the protein expressions of mitochondrial biogenesis (PGC-1α), fusion (Mfn1 and Mfn2), and fission (Drp1) were markedly increased. Meanwhile, the PINK1/Parkin-mediated mitophagy was activated after ASIV administration, which ameliorated ZnONPs-induced SH-SY5Y cell death. Collectively, ASIV administration mitigated ZnONPs-induced cytotoxicity in SH-SY5Y cells through restoring mitochondrial quality control process, which hinted the protective role of ASIV in ZnONPs-induced neurotoxicity. Graphical abstract
研究领域:
药理学
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毒理学
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神经科学
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细胞生物学
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DOI
PubMed
高影响因子
BMC NEUROSCIENCE
·
2017
·Vol. 18
·期 1
·1-10
·
IF 2.312
Xu Zhiming,Liu Yingliang,Yang Dianxu,Yuan Fang,Ding Jun,Chen Hao,Tian Hengli
Background Sesamin is a well-known antioxidant extracted from sesame seeds that exhibits various curative effects. The present study investigated whether sesamin would protect neuroblastoma SH-SY5Y cells against mechanical stretch injury-induced increases in reactive oxygen species (ROS) and apoptosis. Additionally, the mechanisms underlying these actives were investigated. Following exposure to mechanical stretch injury, cells were incubated for further investigations. Lactate dehydrogenase and Cell Counting Kit-8 assays were used to assess cell viability, and a terminal deoxynucleotidyl transferase dUTP nick end labeling assay and flow cytometric analysis were performed to evaluate changes in mitochondrial membrane potential (ΔΨm). Furthermore, intracellular levels of ROS production were measured by 20, 70-dichlorofluorescein diacetate staining, the mRNA levels of matrix metallopeptidase 9 (MMP-9) were evaluated using real-time polymerase chain reaction analysis, and the determinations had also been made on related proteins by Western blot analysis. Results Exposure to mechanical stretch injury significantly decreased cell viability but this decrease was attenuated by pretreatment with sesamin (50 μM). Sesamin also significantly inhibited mechanical stretch injury-induced increases in intracellular ROS production, attenuated declines in ΔΨm, diminished the expressions of pro-apoptotic proteins, and decreased cell apoptosis. Stretch injury increased Bax and cleaved caspase 3 levels, enhanced the gene expression of MMP-9, increased the phosphorylation levels of Akt, p38, and JNK and decreased Bcl-2 levels in the cells. However, pretreatment with sesamin reduced the mechanical stretch injury-induced overexpression of MMP-9. Conclusions Sesamin protected SH-SY5Y cells against stretch injury by attenuating increases in ROS levels and suppressing apoptosis. Accordingly, sesamin seems to be a potentially therapeutic agent in the treatment of traumatic brain injury.
研究领域:
神经生物学
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细胞生物学
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药理学
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DOI
PubMed
高影响因子
PROCESS BIOCHEMISTRY
·
2022
·
IF 4.885
Yatong Yu,Hangyu Shen,Xiaoying Wang,Magdi E. Gibril,Fangong Kong,Shoujuan Wang
Bacterial cellulose (BC) possesses good physical and mechanical properties for tissue engineering, but its negatively charged surface hinders cell adhesion . Here, the surface charge of BC was modulated with 2 −bromoethylamine hydrobromide (2 −BrEA) via a one-step synthesis method performed in alkaline aqueous solutions at room temperature. Positively charged spherical nanoparticles were thus formed in situ on BC. The amination degree of ethylamine-modified BC materials (BC−EAs) reached 2.80 mmol/g; whereas the crystallinity, fiber diameter, and water contact angle were 55.5 − 65.5%, 30 − 45 nm, and 32.5 − 44.9°, respectively. BC−EAs possess good antibacterial effectiveness against Escherichia coli and Staphylococcus aureus . The CCK− 8 and live/dead assays suggest that BC modified with 0.09 g/mL 2 −BrEA (BC−EA3) is biocompatible and possesses a high efficiency for promoting human neuroblastoma SH−SY5Y cell proliferation and differentiation. Its antibacterial ability is beneficial for preventing the formation of biofilms in the extracellular matrix during tissue and organoid formation, while the properties promoting SH−SY5Y cell proliferation and differentiation make BC−EA3 a good candidate for nerve- or other tissue engineering.
研究领域:
材料科学
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生物医学工程
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细胞生物学
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组织工程
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DOI
高影响因子
JOURNAL OF HAZARDOUS MATERIALS
·
2026
·
IF 10.6
Ziyan Cheng,Xinru Wang,Zhimin Yang,Jingtong Yu,Nan Zhao,Chenyang Ji,Quan Zhang,Meirong Zhao
Neonicotinoid insecticides (NNIs) are ubiquitously detected in the environment, yet their comparative neurotoxicity and mechanisms remain insufficiently characterized. This study systematically evaluated the neurotoxic potential of eight common NNIs (imidacloprid, acetamiprid, thiacloprid, thiamethoxam, clothianidin, flonicamid, sulfoxaflor, and imidaclothiz) using human SH-SY5Y cells. Results demonstrated that all tested NNIs significantly reduced cell viability. Mechanistically, NNI exposure triggered excessive reactive oxygen species (ROS) production, inhibited superoxide dismutase (SOD) activity, and elevated malondialdehyde (MDA) levels, indicating severe oxidative stress. Notably, Exposure to NNIs caused a dissipation of mitochondrial membrane potential (MMP) and profoundly disrupted mitochondrial bioenergetics. Analysis of energy metabolism revealed that NNIs suppressed both the oxygen consumption rate (OCR) and extracellular acidification rate (ECAR), suggesting an impairment of oxidative phosphorylation and glycolysis. These findings suggested that NNIs induced neurotoxicity through coordinated oxidative stress and mitochondrial dysfunction, resulting in global bioenergetic suppression characterized by concurrent impairment of oxidative phosphorylation and glycolysis. This study provides critical toxicological evidence for the environmental risk assessment of NNIs and underscores their potential impact on human neurological health.
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PubMed
高影响因子
ENVIRONMENTAL TOXICOLOGY
·
2014
·Vol. 31
·期 4
·496-504
·
IF 2.562
Zhu Enhui,Chen Na,Liu MengYun,Li Jia,Li Dan,Yang Yongsheng,Zhang Ying,He DeFu
As an organochlorine insecticide, endosulfan has been widely banned or restricted, but it is still largely used in many developing countries. Previous studies have shown multiple adverse health effects of endosulfan. However, the neurotoxicity of endosulfan has not been fully elucidated. In this study, endosulfan isomers (α-/β-endosulfan) and their major metabolites (endosulfan sulfate, endosulfan diol, and endosulfan lactone) were, respectively, exposed to human neuroblastoma SH-SY5Y cells. Results showed that both α-endosulfan and β-endosulfan caused decrease of cell viability and morphological damages in a dose-dependent manner. Their median effective concentrations (EC 50s ) were respectively 79.6 μM (α-endosulfan) and 50.37 μM (β-endosulfan) for 72 h exposure. EC 50s of α/β-endosulfan mixture were lower than that of the single isomer. However, EC 50s of its metabolites were higher than that of technical endosulfan. Endosulfan and its metabolites caused increases of reactive oxygen species and the lipid peroxidation, but decrease of superoxide dismutase in a dose-dependent manner. These results indicate that α-endosulfan exhibits higher neurotoxicity than β-endosulfan. Mixture of endosulfan isomers shows stronger cytotoxicity than the single isomer. After endosulfan is degraded, cytotoxicity of its metabolites decreases gradually. The neurotoxicity of endosulfan and its metabolites is closely related to oxidative damage and antioxidative deficit. © 2014 Wiley Periodicals, Inc. Environ Toxicol 31: 496–504, 2016.
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PubMed
高影响因子
MOLECULES
·
2016
·Vol. 21
·期 8
·1071
·
IF 2.465
Liang Cai,Li-Fang Wang,Jun-Ping Pan,Xiang-Nan Mi,Zheng Zhang,Hai-Ju Geng,Jia-Hui Wang,Song-Hui Hu,Wei Zhang,Qin Gao,Wu-Tian Wu,Huan-Min Luo
This study investigated the neuroprotective effects of methyl 3,4-dihydroxybenzoate (MDHB) againstt-butyl hydroperoxide (TBHP) induced oxidative damage in SH-SY5Y (human neuroblastoma cells) and the underlying mechanisms. SH-SY5Y were cultured in DMEM + 10% FBS for 24 h and pretreated with different concentrations of MDHB orN-acetyl-l-cysteine (NAC) for 4 h prior to the addition of 40 μM TBHP for 24 h. Cell viability was analyzed using the methylthiazolyltetrazolium (MTT) and lactate dehydrogenase (LDH) assays. An annexin V-FITC assay was used to detect cell apoptosis rates. The 2′,7′-dichlorofluorescin diacetate (DCFH-DA) assay was used to determine intracellular ROS levels. The activities of antioxidative enzymes (GSH-Px and SOD) were measured using commercially available kits. The oxidative DNA damage marker 8-OHdG was detected using ELISA. Western blotting was used to determine the expression of Bcl-2, Bax, caspase 3, p-Akt and Akt proteins in treated SH-SY5Y cells. Our results showed that MDHB is an effective neuroprotective compound that can mitigate oxidative stress and inhibit apoptosis in SH-SY5Y cells.Keywords:methyl 3,4-dihydroxybenzoate;oxidative stress;apoptosis;neuroprotection;nuclear factor erythroid 2-related factor 2
研究领域:
神经科学
·
药理学
·
细胞生物学
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产品关联
DOI
PubMed
高影响因子
NATURAL PRODUCT RESEARCH
·
2021
·
IF 2.862
Yi Lin,Jingjing Liang,Xiaogang Peng,Hanli Ruan
Three new phenolic compounds, 2,3,4-trihydroxy-1-(4′-hydroxybenzyl)benzoic acid (1), 2,3,4-trihydroxy-1-(4′-hydroxy-3′-methoxybenzyl)benzoic acid (2), and 2-(4′-hydroxy-3′-methoxybenzyl)-3,5-dimethoxy-1,4-benzoquinone (3), were isolated from the fresh pericarps of Juglans sigillata Dode. Their structures were elucidated by integrated spectroscopic techniques. Bioactivity screening results showed that compounds 1–3 exhibited moderate neuroprotective effects against H2O2-induced or CoCl2-induced cellular damage in human neuroblastoma SH-SY5Y cell line.
研究领域:
植物化学
·
药理学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF NEUROIMMUNOLOGY
·
2026
·
IF 3.1
Guihua Wu,Fuwei Wang,Zihao Chen,Nan Zheng,Qiong Zhou,Lihua Xie,Xinyu Yang,Daibo Song,Qiang Sun,Jiantao Lin,Li Li
Alzheimer's disease (AD) is a devastating neurodegenerative disorder that currently lacks efficacious therapeutic interventions. It's well documented that ferroptosis is extensively involved in the progression and pathogenesis of AD. Betaine, a critical nutrient for mammal health, is reported to possess neuroprotective actions. The objective of the current research was to investigate whether betaine could mitigate neuronal impairments by suppressing ferroptosis in SH-SY5Y neuroblastoma cells injured by glutamate. The results indicate that betaine improved the survival rate and reversed morphology changes of glutamate-damaged SH-SY5Y cells. Additionally, betaine reduced the intracellular accumulation of Fe 2+ , malondialdehyde (MDA), lipid reactive oxygen species (ROS), and lactate dehydrogenase (LDH) release induced by glutamate. And reversed the decreased glutathione (GSH) content and downregulation of ferroptosis inhibitor glutathione peroxidase 4 (GPX4) expression were observed upon betaine administration. Additionally, betaine facilitated the translocation of nuclear factor erythroid 2-related factor 2 (Nrf2) from the cytoplasm to the nucleus in SH-SY5Y cells induced by glutamate. Molecular docking validated high-affinity binding between betaine and Nrf2. Collectively, betaine could exert neuroprotective effects by alleviating ferroptosis via activation of the Nrf2 pathway, thereby positioning it as a potential candidate for targeting ferroptosis-driven neurodegeneration in AD.
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高影响因子
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