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.
研究领域:
神经毒理学
·
细胞生物学
·
分子生物学
·
环境毒理学
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产品关联
DOI
PubMed
高影响因子
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.
研究领域:
神经生物学
·
细胞生物学
·
电化学分析
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DOI
PubMed
高影响因子
NEUROCHEMICAL RESEARCH
·
2020
·Vol. 46
·期 2
·367-378
·
IF 3.038
Xiang Biao,Li Daowen,Chen Yiqiang,Li Meng,Zhang Yuan,Sun Tun,Tang Shusheng
Impaired homeostasis of copper has been linked to different pathophysiological mechanisms in neurodegenerative diseases and oxidative injury has been proposed as the main mechanism. This study aims to use curcumin, a widely used antioxidative and anti-apoptotic agent, to exert the neuroprotective effect against copper in vitro and illuminate the underlying mechanism. The effect of curcumin was examined by using a cell counting kit-8 assay, flow cytometry, immunofluorescence, spectrophotometer, and western blot. Results revealed that after pretreatment with curcumin for 3 h, copper-induced toxicity and apoptosis show a significant decline. Further experiments showed that curcumin not only decreased the production of ROS and MDA but also increased the activities of the ROS scavenging enzymes SOD and CAT. Moreover, curcumin treatment alleviated the decrease in mitochondrial membrane potential and the nuclear translocation of cytochrome c induced by copper. The protein levels of pro-caspase 3, pro-caspase 9, and PARP1 were up-regulated and the Bax/Bcl-2 ratio was down-regulated in the presence of curcumin. Taken together, our study demonstrates that curcumin has neuroprotective properties against copper in SH-SY5Y cells and the potential mechanisms might be related to oxidative stress and mitochondrial apoptosis.
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
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.
研究领域:
神经科学
·
毒理学
·
分子生物学
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产品关联
DOI
PubMed
高影响因子
Brain Sciences
·
2023
·Vol. 13
·期 3
·382
·
IF 3.3
Jian-Chao Peng,Yue Deng,Han-Xiao Song,Yuan-Yuan Fang,Cui-Liu Gan,Jun-Jie Lin,Jing-Jing Luo,Xiao-Wei Zheng,Michael Aschner,Yue-Ming Jiang
Background: Combined exposure to lead and cadmium is common in occupational environments. However, the effects of co-exposure to Pb-Cd on neurotoxicity have not been fully clarified. Sodium para-aminosalicylic acid (PAS-Na) has previously been shown to protect neurons from Pb-induced toxicity. This study aimed to investigate the beneficial effect of PAS-Na against co-exposure to Pb-Cd-induced neurodegeneration in SH-SY5Y cells. Methods: The MTT assay was used to detect the effects of Pb and Cd alone, or in combination, on SH-SY5Y cell survival. The effects of Pb and Cd alone or in combination on oxidative stress were assessed by reactive oxygen species (ROS) level. Nrf2, the master switch for antioxidant responses, was detected by immunofluorescence. Protein expression levels of PI3K, Akt, p-Akt, Nrf2 and HO-1 were determined by Western blot analysis. Results: MTT assay results established that the survival rate of SH-SY5Y cells was not significantly affected by exposure to 1 μmol/L lead, 0.25 μmol/L cadmium, and 1-fold Pb-Cd mixture (1 μmol/L Pb + 0.25 μmol/L Cd), while 10-fold Pb-Cd combined exposure (10 μmol/L Pb + 2.5 μmol/L Cd) significantly reduced the survival rate of SH-SY5Y cells. Combined Pb-Cd exposure significantly increased intracellular ROS levels, and N-Acetyl-L-cysteine (NAC) treatment in the 10 μmol/L Pb + 2.5 μmol/L Cd group significantly decreased ROS expression levels, attenuating the levels of oxidative stress. Protein expression of PI3K and p-Akt significantly decreased in the 10 μmol/L Pb + 2.5 μmol/L Cd group, while the expression of PI3K and p-Akt protein increased after PAS-Na intervention. Immunofluorescence analysis showed that levels of Nrf2 in the nucleus increased in the 10 μmol/L Pb + 2.5 μmol/L Cd group, along with Nrf2 protein levels, suggesting that Nrf2 was translocated from the cytoplasm into the nucleus upon combined Pb-Cd exposure. In addition, HO-1 protein expression level, a downstream gene product of Nrf2, was increased. In response to NAC intervention, HO-1 protein expression levels significantly decreased. PAS-Na had the same intervention effect as NAC. Conclusion: Combined exposure to Pb-Cd induced oxidative stress and cytotoxicity in SH-SY5Y cells. PAS-Na displayed antagonistic effects on neurodegenerative changes induced by combined Pb-Cd exposure; hence, it may afford a novel treatment modality for exposure to these metals.Keywords:lead;cadmium;oxidative stress;co-exposure
研究领域:
神经科学
·
毒理学
·
细胞生物学
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产品关联
DOI
PubMed
高影响因子
Molecular Medicine Reports
·
2019
·Vol. 20
·期 1
·529-538
·
IF 1.851
Shasha Chen,Feng Cai,Jirong Wang,Zhouxin Yang,Chi Gu,Guofu Wang,Genxiang Mao,Jing Yan
The abnormal aggregation of α‑synuclein (α‑syn), which is an important pathological feature of Parkinson's disease (PD), is cytotoxic to dopaminergic neurons and causes cellular damage and apoptosis. Salidroside (SAL) is the main active component of the traditional Chinese medicine Rhodiola rosea. Previous research has demonstrated that SAL exerts cellular protection against cell senescence and neurodegeneration. However, the role and mechanism of action of SAL in PD remain unclear. The present study used overexpression of the wild‑type and the A53T mutation of α‑syn to induce a neuronal model of PD in SH‑SY5Y cells, which led to neuronal toxicity and a reduced cell proliferation index. SAL increased the cell proliferation index of both PD model groups in a dose‑dependent manner. Additionally, SAL alleviated pathogenic phosphorylated (Ser129) α‑syn expression as well as the ratio of microtubule‑associated proteins 1A/1B light chain 3 (LC3)‑I to LC3‑II expression, which is related to autophagic function. Furthermore, the results suggested that the underlying mechanism for the SAL‑induced protection of PD model neurons may involve the preservation of autophagy, which attenuates the phosphorylation of α‑syn in neurons predominantly via mTOR/p70S6K, and is independent of the PI3K/Akt signaling pathway.
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
PHARMACEUTICAL CHEMISTRY JOURNAL
·
2023
·Vol. 57
·期 5
·712-724
·
IF 0.9
Li Danqi,Li Weihong,Shi Wenhao,Wu XiaoJing,Liu Xuegui,Gao Pinyi
Depression is a common mental health disease, with the characteristics of significant and persistent low mood. Traditionally, Ziziphus jujuba Mill . was used to treat depression. However, its chemical pharmacologic profiles remain to be elucidated. The present study was aimed to explore the potential targets and mechanisms of Z. jujuba in the treatment of depression using network pharmacology and in vitro neuroprotective experiment. In this study, 11 compounds of Z. jujuba were obtained by multiple column chromatography. Based on the network pharmacology, the C-T network was established by the results of molecular docking. The information on target proteins was enriched via DAVID database, followed by the analysis of GO and KEGG. The results indicated that 10 compounds, 5 target proteins and 3 signaling pathways played important roles in treating depression. Based on the predicted result of network pharmacology, compounds 1 , 9 and 10 were identified with significant neuroprotective effects by in vitro cell experiments with human neuroblastoma cell line SH-SY5Y. This study was the first to investigate the mechanisms of Z. jujuba action in the treatment of depression from the system level, and could provide the basis of the mechanism with action of compounds for the in-depth utilization of Z. jujuba.
研究领域:
中药学
·
神经科学
·
生物信息学
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DOI
高影响因子
ENVIRONMENTAL POLLUTION
·
2024
·
IF 7.6
Ling Wang,Binquan Wang,Xiaoyan Zhang,Ziyi Yang,Xing Zhang,Hongyang Gong,Yuanyuan Song,Ke Zhang,Mingkuan Sun
Tris (1,3-dichloro-2-propyl) phosphate (TDCPP), a halogen-containing phosphorus flame retardant, is widely used and has been shown to possess health risks to humans. The sustained release of artificial nanomaterials into the environment increases the toxicological risks of their coexisting pollutants. Nanomaterials may seriously change the environmental behavior and fate of pollutants. In this study, we investigated this combined toxicity and the potential mechanisms of toxicity of TDCPP and titanium dioxide nanoparticles (TiO 2 NPs) aggregates on human neuroblastoma SH-SY5Y cells. TDCPP and TiO 2 NPs aggregates were exposed in various concentration combinations, revealing that TDCPP (25 μg/mL) reduced cell viability, while synergistic exposure to TiO2 NPs aggregates exacerbated cytotoxicity. This combined exposure also disrupted mitochondrial function, leading to dysregulation in the expression of mitochondrial fission proteins (DRP1 and FIS1) and fusion proteins (OPA1 and MFN1). Consequently, excessive mitochondrial fission occurred, facilitating the translocation of cytochrome C from mitochondria to activate apoptotic signaling pathways. Furthermore, exposure of the combination of TDCPP and TiO 2 NPs aggregates activated upstream mitochondrial autophagy but disrupted downstream Parkin recruitment to damaged mitochondria, preventing autophagosome-lysosome fusion and thereby disrupting mitochondrial autophagy. Altogether, our findings suggest that TDCPP and TiO 2 NPs aggregates may stimulate apoptosis in neuronal SH-SY5Y cells by inducing mitochondrial hyperfission and inhibiting mitochondrial autophagy.
研究领域:
毒理学
·
神经科学
·
细胞生物学
·
环境科学
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产品关联
DOI
PubMed
高影响因子
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.
研究领域:
神经科学
·
药理学
·
细胞生物学
·
帕金森病研究
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Oxidative Medicine and Cellular Longevity
·
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.
研究领域:
药理学
·
毒理学
·
细胞生物学
·
神经科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
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
研究领域:
生物材料
·
神经科学
·
组织工程
·
生物医学工程
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产品关联
DOI
PubMed
高影响因子
Metallomics
·
2019
·Vol. 12
·期 2
·173-182
·
IF 3.571
Lv Xiaoguang,Zheng Qiaoqiao,Li Ming,Huang Zhiwei,Peng Min,Sun Jing,Shi Ping
Clioquinol is recently considered to be the most promising drug for treating cancer and neurodegenerative diseases. However, its mode of action varies from different disease models. In this study, we found that clioquinol inhibited cell growth in human neurotypic SHSY-5Y cells, which was attributed to both S-phase cell-cycle arrest and autophagic cell death. Clioquinol increased the intracellular contents of iron and zinc as well as calcium as measured by ICP-AES. Staining of Fluo-3 confirmed an increase in the level of calcium. Analysis of the metal-binding ability of clioquinol showed that it was not a chelating agent of calcium ions and the elevation of intracellular calcium content is not achieved by clioquinol as an ionophore. CaCl2 could simulate or even aggravate the cytotoxicity of clioquinol and it increased S-phase cell cycle arrest induced by clioquinol in a concentration dependent manner. Staining of acridine orange demonstrated that autophagy induced by clioquinol was not affected by addition of calcium ions. In contrast, the intracellular calcium ion chelator BAPTA-am abolished the clioquinol-induced S phase arrest and reduced the cell death caused by clioquinol. The WB assay of cell cycle-related proteins (CDK2, p21 and p27) further confirmed that S phase arrest is positively correlated with intracellular calcium elevation, which was due to the alterations of the mRNA and protein levels of calcium pumps (SERCA and SPCA). Taken together, these data indicate that clioquinol regulates the level of intracellular calcium ions to induce S-phase cell cycle arrest in human SH-SY5Y cells. Our results demonstrate for the first time that an increase of intracellular calcium content is one of the mechanisms of clioquinol in the inhibition of human neurotypic SHSY-5Y cells.
研究领域:
肿瘤学
·
神经科学
·
细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）