Experimental and Therapeutic Medicine
·
2019
·Vol. 18
·期 5
·3643-3649
·
IF 1.448
Cui Huang,Jing Ma,Bai‑Xiang Li,Yan Sun
Wingless (Wnt) signaling regulates the proliferation and differentiation of midbrain dopamine (DA) neurons. Paraquat (PQ) and maneb (MB) are environmental pollutants that can be used to model Parkinson's disease (PD) in rodents. A previous study demonstrated that developmental exposure to PQ and MB affects the expression of Wnt1, Wnt5a, nuclear receptor‑related factor 1 (NURR1) and tyrosine hydroxylase (TH). However, how Wnt signaling regulates these developmental factors in vitro is yet to be determined. To explore this, SH‑SY5Y cells were exposed to PQ and MB. The results of the current study indicated that exposure to PQ and MB decreased Wnt1, β‑catenin, NURR1 and TH levels and increased Wnt5a levels. Furthermore, Wnt1 silencing has the same effect as exposure to PQ and MB. Additionally, the neurotoxicity induced by PQ and MB is more severe in siWnt1‑SH‑SY5Y cells compared with normal SH‑SY5Y cells. Therefore, Wnt1 may serve an important role in regulating developmental DA factors, and may be a candidate gene for PD diagnosis or gene therapy.
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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.
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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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ENVIRONMENTAL TOXICOLOGY
·
2023
·
IF 4.5
Zhihui Li,Yan Shi,Yougang Wang,Haomin Qi,Haiyu Chen,Jinquan Li,Li Li
Cadmium (Cd) is a hypertoxic heavy metal that may be exposed to environmental pollutants by humans and animals. It can lead to cognitive disfunction, and is linked to neurodegenerative diseases. Cadmium reportedly can induce endoplasmic reticulum (ER) stress, but few studies have concentrated on it in nerve cells, and the connection between ER stress and neuroinflammation. In this study, in vitro experiments on SH-SY5Y neuroblastoma cells were carried out. We aimed at exploring whether Cd attributed to the cell pyroptosis and the role of PERK in promoting this form of cell damage which can induce strong inflammatory responses. Our results demonstrated that CdCl 2 treatment induced excess reactive oxygen species (ROS) production, caused significant modifications in the expression of PERK and increased TXNIP, NLRP3, IL-1β, IL-18, and caspase1 in SH-SY5Y cells. In addition, scavenging ROS with N -acetylcysteine or inhibiting the expression of PERK by using GSK2606414, rescued the SH-SY5Y cells from cadmium-induced pyroptosis. In conclusion, the results suggest that Cd induces pyroptotic death of SH-SY5Y cells through ER stress, and this may be the potential mechanism of Cd incurring neurological diseases.
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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.
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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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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.
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Oxidative Medicine and Cellular Longevity
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2021
·
IF 6.543
Zhen-Dong Zhang,Ya-Jun Yang,Zhe Qin,Xi-Wang Liu,Shi-Hong Li,Li-Xia Bai,Jian-Yong Li
Aspirin eugenol ester (AEE) is a new pharmaceutical compound esterified by aspirin and eugenol, which has anti-inflammatory, antioxidant, and other pharmacological activities. The aim of this study was to investigate the protective effect of AEE on paraquat- (PQ-) induced cell damage of SH-SY5Y human neuroblastoma cells and its potential molecular mechanism. There was no significant change in cell viability when AEE was used alone. PQ treatment reduced cell viability in a concentration-dependent manner. However, AEE reduced the PQ-induced loss of cell viability. Flow cytometry, terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL), and 46-diamidino-2-phenylindole (DAPI) staining were used to evaluate cell apoptosis. Compared with the PQ group, AEE pretreatment could significantly inhibit PQ-induced cell damage. AEE pretreatment could reduce the cell damage of SH-SY5Y cells induced by PQ via reducing superoxide anion, intracellular reactive oxygen species (ROS), and mitochondrial ROS (mtROS) and increasing the levels of mitochondrial membrane potential (). At the same time, AEE could increase the activity of glutathione peroxidase (GSH-Px), catalase (CAT), and superoxide dismutase (SOD) and decrease the activity of malondialdehyde (MDA). The results showed that compared with the control group, the expression of p-PI3K, p-Akt, and Bcl-2 was significantly decreased, while the expression of caspase-3 and Bax was significantly increased in the PQ group. In the AEE group, AEE pretreatment could upregulate the expression of p-PI3K, p-Akt, and Bcl-2 and downregulate the expression of caspase-3 and Bax in SH-SY5Y cells. PI3K inhibitor LY294002 and the silencing of PI3K by shRNA could weaken the protective effect of AEE on PQ-induced SH-SY5Y cells. Therefore, AEE has a protective effect on PQ-induced SH-SY5Y cells by regulating the PI3K/Akt signal pathway to inhibit oxidative stress.
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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
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MOLECULAR AND CELLULAR BIOCHEMISTRY
·
2011
·Vol. 363
·期 1
·309-313
·
IF 2.168
Zhao Hui,Li Ling,Fan Hua-Jun,Wang Fei,Jiang Li-Ming,He Pin-Gang,Fang Yu-Zhi
Communication between cells by release of specific chemical messengers via exocytosis plays crucial roles in biological process. Catecholamines, like dopamine, epinephrine, and norepinephrine, which are types of neurotransmitters released from cells, can be oxidized and detected by the microelectrodes, and amperometric detection of exocytosis is an effective method for studying the communication between cells. The experimental results depend on many factors, among which the property of the microelectrode, cell states, and their positions to each other are particularly important. A type of indium tin oxide (ITO) micro-pore electrodes, which is characterized by its stability, has been developed with photolithography. SH-SY5Y cells can adhere and spread on ITO micro-pore electrodes. Therefore, it is possible to investigate the correlation between cell morphology and exocytosis. The results show that cells with clear process have higher release frequency of norepinephrine compared with cells in spherical shape. Combined with fluorescence observation, this technique provides a simple and convenient methodology for cell study.
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MOLECULAR NEUROBIOLOGY
·
2025
·
IF 4.3
Li Xinying,Li Weiran,Xie Xinying,Fang Ting,Yang Jingwen,Shen Yue,Wang Yicheng,Wang Hongyan,Tao Liqing,Zhang Heng
Rotenone, a plant-derived natural insecticide, is widely used to induce Parkinson’s disease (PD) models. However, the mechanisms of rotenone-induced cell death remain unclear. Here, we found that rotenone (0.01, 0.1, or 1 μmol/L) suppressed SH-SY5Y dopamine neuron viability and led to PD-like pathological changes, such as reduced tyrosine hydroxylase (TH) but increased α-synuclein. Rotenone increased the levels of intracellular reactive oxygen species (ROS) and mitochondrial ROS, as well as the levels of the antioxidants nuclear factor E2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1), ultimately resulting in oxidative stress. Moreover, rotenone significantly downregulated the expression of GPX4 and xCT but upregulated the expression of COX2 and NCOA4, which are markers of ferroptosis. Furthermore, rotenone decreased phosphorylated mTOR level but increased Beclin-1, ATG5, LC3 and p62 expression, suggesting that rotenone enhances autophagy and reduces autophagy flux. Additionally, rotenone reduced Bcl-2 levels and the mitochondrial membrane potential (MMP) while promoting BAX and Caspase-3 expression, thus initiating cell apoptosis. N-acetylcysteine (NAC), a ROS scavenger, and ferrostatin-1 (Fer-1) and deferoxamine (DFO), two ferroptosis inhibitors, significantly eliminated rotenone-induced autophagy and apoptosis. Moreover, ML385, a specific inhibitor of Nrf2, suppressed rotenone-induced ferroptosis. Our results demonstrated that ROS might mediate rotenone-induced PD-like pathological changes by regulating iron death, autophagy, and apoptosis. Inhibiting ferroptosis blocked the rotenone-induced increase in autophagy and apoptosis. Thus, the ability of ROS to regulate rotenone-induced death through autophagy and apoptosis is dependent on ferroptosis. The findings require validation in multiple neuronal cell lines and in vivo.
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Polymers
·
2022
·Vol. 14
·期 9
·1882
·
IF 4.967
Zhiyuan Zhao,Tong Wu,Yu Cui,Rui Zhao,Qi Wan,Rui Xu
The development and treatment of some diseases, such as large-area cerebral infarction, cerebral hemorrhage, brain tumor, and craniocerebral trauma, which may involve the injury of the dura mater, elicit the need to repair this membrane by dural grafts. However, common dural grafts tend to result in dural adhesions and scar tissue and have no further neuroprotective effects. In order to reduce or avoid the complications of dural repair, we used PLGA, tetramethylpyrazine, and chitosan as raw materials to prepare a nanofibrous dura mater (NDM) with excellent biocompatibility and adequate mechanical characteristics, which can play a neuroprotective role and have an antifibrotic effect. We fabricated PLGA NDM by electrospinning, and then chitosan was grafted on the nanofibrous dura mater by the EDC-NHS cross-linking method to obtain PLGA/CS NDM. Then, we also prepared PLGA/TMP/CS NDM by coaxial electrospinning. Our study shows that the PLGA/TMP/CS NDM can inhibit the excessive proliferation of fibroblasts, as well as provide a sustained protective effect on the SH-SY5Y cells treated with oxygen–glucose deprivation/reperfusion (OGD/R). In conclusion, our study may provide a new alternative to dural grafts in undesirable cases of dural injuries.Keywords:nanofibrous dura mater;antifibrosis;neuroprotection;PLGA;tetramethylpyrazine
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