scholarly journals Role of trehalose in MPTP-induced injury of SH-SY5Y cells and its mechanism

2021 ◽  
Vol 3 (1) ◽  
pp. 9-25
Author(s):  
Anxia Hu ◽  
Changhao Yin ◽  
Benxuan Wang ◽  
Xing Liu
Keyword(s):  
Survival Rate ◽  
Culture Medium ◽  
Cell Model ◽  
Neuroblastoma Cells ◽  
Control Group ◽  
Human Neuroblastoma ◽  
Er Stress Response ◽  
Related Proteins ◽  
Significant Protective Effect

Objective: To establish a Parkinson's disease (PD) cell model of human neuroblastoma cells (SH-SY5Y) induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), and to explore the possible mechanism of trehalose in PD. Methods: SH-SY5Y cells were cultured and divided into four groups: control group, trehalose group, MPTP group and trehalose +MPTP group.The trehalose was detected with MTT assay for its effect of on the viability of injured SH-SY5Y cells. The lactate dehydrogenase (LDH) was detected by kit for its level in culture medium. The ROS was assessed by DCFH-DA for its average level in cells. Besides, Hoechst 33342 staining was used to detect apoptosis. The endoplasmic reticulum stress (ERS) related proteins GRP78, IRE1, PERK and ATF6 were also detected by Western blot for its expression levels. Results: The survival rate of MPTP group decreased significantly and the levels of LDH and ROS increased compared with the control group. In addition, the survival rate of cells in trehalose +MPTP group increased significantly and the levels of LDH and ROS decreased compared with MPTP group. The expressions of GRP78, IRE1, p- IRE1, PERK, p- PERK and ATF6 in MPTP group increased, but decreased in trehalose +MPTP group compared with the control group. Conclusion: Trehalose has a significant protective effect on MPTP-induced SH-SY5Y cells injury, and its mechanism may be related to the effect of trehalose on oxidative stress by inhibiting ER stress response.

scholarly journals Methylmercury Induced Apoptosis of Human Neuroblastoma Cells Through the ROS Mediated Caspase and PARP/AIF Dependent Pathways

2021 ◽  
Author(s):  
Shanshan Hou ◽  
Xiayu Zhang ◽  
Xiaofan Ning ◽  
Hao Wu ◽  
Xinyue Li ◽  
...  
Keyword(s):  
Neuronal Apoptosis ◽  
Neuroblastoma Cells ◽  
Human Neuroblastoma Cells ◽  
Irreversible Damage ◽  
Human Neuroblastoma ◽  
Apoptosis Inhibition ◽  
Caspase Pathway ◽  
Induced Apoptosis ◽  
Related Proteins

Abstract Methylmercury (MeHg) is an environmental neurotoxic substance, which can be absorbed by the human body through the digestive tract, and easily cross the blood-brain barrier, causing irreversible damage to the human central nervous system. Reactive oxygen species (ROS) are involved in various ways of intracellular physiological or pathological processes including neuronal apoptosis. The current studies attempted to explore the role of ROS-mediated PARP/AIF apoptosis signal in the process of MeHg inducing human neuroblastoma cells (SH-SY5Y) death. Here, the present studies found that SH-SY5Y cells underwent apoptosis in response to MeHg, which was accompanied by increased the levels of ROS and calcium ion, and the activation of caspase cascades and poly ADP-ribose polymerase (PARP). The decrease in ROS levels significantly reduced the expression of these proteins and the rate of apoptosis. Inhibition of caspase pathway can reduce the rate of apoptosis, but can not prevent the occurrence of apoptosis. Furthermore, inhibition of PARP signaling can significantly reduce the apoptosis rate and the expression of caspase pathway related proteins. Collectively, these results indicated that ROS mediated activation of caspase pathway and PARP /AIF signaling pathway are involved in MeHg induced apoptosis, and there is a certain relationship between the two pathways.

scholarly journals proBDNF expression induces apoptosis and inhibits synaptic regeneration by regulating the RhoA-JNK pathway in an in vitro post-stroke depression model

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Bangkun Yang ◽  
Lesheng Wang ◽  
Ying Nie ◽  
Wei Wei ◽  
Wenping Xiong
Keyword(s):  
Neural Plasticity ◽  
Cell Model ◽  
Neurotrophin Receptor ◽  
Control Group ◽  
P75 Neurotrophin Receptor ◽  
Post Stroke ◽  
Post Stroke Depression ◽  
Cellular Apoptosis ◽  
Related Proteins

AbstractBrain-derived neurotrophic factor (BDNF) plays an important role in the pathophysiology of post-stroke depression (PSD). However, the precise function and potential mechanism of proBDNF, the precursor form of BDNF, are unknown. In our study, a PSD-like model was established by treating neuronal cells with oxygen-glucose deprivation and corticosterone. We found that the protein proBDNF levels were significantly higher in the cortex and hippocampus in the PSD group than in the control group, suggesting that proBDNF plays a role in the pathophysiology of PSD. Furthermore, we re-established the PSD-like cell model using recombinant p75 neurotrophin receptor (p75NTR) or silencing c-Jun N-terminal kinase (JNK), and found that the PSD-induced upregulation of proBDNF was inhibited by recombinant p75NTR and JNK silencing (siJNK), and increased cellular apoptosis. Moreover, the application of recombinant p75NTR and siJNK in the PSD-like cell model significantly reversed the expression of apoptosis-related and depression-related proteins and decreased cellular apoptosis. Our findings suggest that proBDNF is involved in neural plasticity in PSD in vitro. The RhoA-JNK signaling pathway is activated after proBDNF binds to the p75NTR receptor, followed by the expression of apoptosis-related proteins (PSD95, synaptophysin, and P-cofilin), which contribute to PSD progression. The mechanism might involve the promotion of cellular apoptosis and the inhibition of nerve synapses regeneration by proBDNF.

Role of the mitochondrial Ca2+ uniporter in Pb2+-induced oxidative stress in human neuroblastoma cells

2014 ◽  
Vol 1575 ◽  
pp. 12-21 ◽  
Author(s):  
Xinyi Yang ◽  
Bin Wang ◽  
Hongqiang Zeng ◽  
Chunqing Cai ◽  
Qiansheng Hu ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Neuroblastoma Cells ◽  
Human Neuroblastoma Cells ◽  
Human Neuroblastoma

scholarly journals Repression of BIRC5/Survivin by FOXO3/FKHRL1 Sensitizes Human Neuroblastoma Cells to DNA Damage-induced Apoptosis

2009 ◽  
Vol 20 (7) ◽  
pp. 2041-2048 ◽  
Author(s):  
Petra Obexer ◽  
Judith Hagenbuchner ◽  
Thomas Unterkircher ◽  
Nora Sachsenmaier ◽  
Christoph Seifarth ◽  
...  
Keyword(s):  
Nuclear Translocation ◽  
Chemotherapy Resistance ◽  
Neuroblastoma Cells ◽  
Phosphatidylinositol 3 Kinase ◽  
Human Neuroblastoma Cells ◽  
Hairpin Rna ◽  
Human Neuroblastoma ◽  
Dna Damaging Agents ◽  
Induced Apoptosis

The phosphatidylinositol 3-kinase (PI3K)–protein kinase B (PKB) pathway regulates survival and chemotherapy resistance of neuronal cells, and its deregulation in neuroblastoma (NB) tumors predicts an adverse clinical outcome. Here, we show that inhibition of PI3K-PKB signaling in human NB cells induces nuclear translocation of FOXO3/FKHRL1, represses the prosurvival protein BIRC5/Survivin, and sensitizes to DNA-damaging agents. To specifically address whether FKHRL1 contributes to Survivin regulation, we introduced a 4-hydroxy-tamoxifen-regulated FKHRL1(A3)ERtm allele into NB cells. Conditional FKHRL1 activation repressed Survivin transcription and protein expression. Transgenic Survivin exerted a significant antiapoptotic effect and prevented the accumulation of Bim and Bax at mitochondria, the loss of mitochondrial membrane potential as well as the release of cytochrome c during FKHRL1-induced apoptosis. In concordance, Survivin knockdown by retroviral short hairpin RNA technology accelerated FKHRL1-induced apoptosis. Low-dose activation of FKHRL1 sensitized to the DNA-damaging agents doxorubicin and etoposide, whereas the overexpression of Survivin diminished FKHRL1 sensitization to these drugs. These results suggest that repression of Survivin by FKHRL1 facilitates FKHRL1-induced apoptosis and sensitizes to cell death induced by DNA-damaging agents, which supports the central role of PI3K-PKB-FKHRL1 signaling in drug resistance of human NB.

Artemisia capillaris Thunberg Produces Sedative-Hypnotic Effects in Mice, Which are Probably Mediated Through Potentiation of the GABAA Receptor

2015 ◽  
Vol 43 (04) ◽  
pp. 667-679 ◽  
Author(s):  
Irene Joy I. dela Peña ◽  
Eunyoung Hong ◽  
Hee Jin Kim ◽  
June Bryan de la Peña ◽  
Tae Sun Woo ◽  
...  
Keyword(s):  
Ion Channel ◽  
Motor Coordination ◽  
Neuroblastoma Cells ◽  
Control Group ◽  
Human Neuroblastoma ◽  
Reference Drug ◽  
Artemisia Capillaris ◽  
Oral Control ◽  
Ion Influx ◽  
Eeg Recordings

The Artemisia group of plants has long been used as a traditional remedy for various conditions. The present study assessed the sleep-promoting (sedative-hypnotic) effects of Artemisia capillaris Thunberg (A. capillaris), and elucidated a possible mechanism behind its effect. ICR mice were given A. capillaris extract (oral) at different dosages (50, 100, 200, 300, or 400 mg/kg), distilled water (oral; control), or diazepam (intraperitoneal; reference drug). One hour after administration, locomotion (open-field test) and motor coordination (rota-rod test) were assessed. The extract's effect on pentobarbital-induced sleep was also evaluated. Additionally, electroencephalographic (EEG) recordings were measured in rats. To evaluate a possible mechanism behind its effects, changes in chloride ( Cl -) ion influx were measured in human neuroblastoma cells. As compared to the control group, mice treated with A. capillaris demonstrated significantly decreased locomotor activity and impaired motor balance and coordination. The extract also shortened the onset and lengthened the duration of sleep induced by pentobarbital sodium. These effects were comparable to that induced by diazepam. Furthermore, A. capillaris-treated rats showed increased delta and decreased alpha EEG waves; an electroencephalographic pattern indicative of relaxation or sedation. In neuroblastoma cells, the extract dose-dependently increased Cl - ion influx, which was blocked by co-administration of bicuculline, a GABAA receptor competitive antagonist, suggesting that its effects are mediated through the GABAA receptor– Cl - ion channel complex. Altogether, the results of the present study demonstrate that A. capillaris possesses potent sedative-hypnotic effects, which are probably mediated through potentiation of the GABAA receptor– Cl - ion channel complex.

scholarly journals The essential role of ERK in 4-oxo-2-nonenal-mediated cytotoxicity in SH-SY5Y human neuroblastoma cells

2009 ◽  
Vol 108 (6) ◽  
pp. 1434-1441 ◽  
Author(s):  
Hyun-Pil Lee ◽  
Xiaochun Zhu ◽  
Xiongwei Zhu ◽  
S. Chad Skidmore ◽  
George Perry ◽  
...  
Keyword(s):  
Essential Role ◽  
Neuroblastoma Cells ◽  
Human Neuroblastoma Cells ◽  
Human Neuroblastoma

Generation and metabolism of Ins(1,4,5)P3 in SH-SY5Y human neuroblastoma cells: The regulatory role of Ca2+

1991 ◽  
Vol 19 (4) ◽  
pp. 424S-424S ◽  
Author(s):  
DAVID G. LAMBERT ◽  
RICHARD J. H. WOJCIKIEWICZ ◽  
STEFAN R. NAHORSKI
Keyword(s):  
Neuroblastoma Cells ◽  
Regulatory Role ◽  
Human Neuroblastoma Cells ◽  
Human Neuroblastoma

scholarly journals Class I HDAC Inhibitor Rescues Synaptic Damage and Neuron Loss in APP-Transfected Cells and APP/Ps1 Mice through the GRIP1/AMPA Pathway

2021 ◽  
Author(s):  
Ying Han ◽  
Le Chen ◽  
Jingyun Liu ◽  
Chunyang Wang ◽  
Yu Guo ◽  
...  
Keyword(s):  
Ampa Receptor ◽  
Ampa Receptors ◽  
Hippocampal Neurons ◽  
Cell Model ◽  
Cytoskeletal Proteins ◽  
Synaptic Proteins ◽  
Human Neuroblastoma ◽  
Transfected Cells ◽  
Related Proteins

Abstract As a neurodegenerative disease, Alzheimer's disease (AD) seriously affects the health of older people. It is now known that changes in synapses occur first in the course of disease, perhaps even before the formation of Aβ plaques. Histone deacetylase (HDAC) can mediate the damage of Aβ oligomers to dendritic spines. Therefore, we examined the relationship between HDAC activity and synaptic defects by using an HDACI, BG45 in Human neuroblastoma SH-SY5Y cell line with stable overexpression of Swedish mutant APP (APPsw) and in APP/Ps1 transgenic mice during this study. The cells were treated with 15µM BG45 and the APP/Ps1 mice 30mg/kg BG45. We detected the level of synapse-related proteins, HDACs, tau phosphorylation and AMPA receptors by western bloting and immunohistochemistry. We also measured the expression of cytoskeletal proteins in the cell model. The mRNA level of GRIK2, SCN3B, SYNPR, Grm2, Grid2IP, GRIP1,GRIP2 were. to explore the effects of HDACi on regulating the synaptic proteins and AMPA receptors. Our studies demonstrated that the expression of HDAC1、HDAC2 and HDAC3 was increased, which was accompanied by the downregulation of the synapse-related proteins synaptophysin (SYP), postsynaptic dendritic protein (PSD-95) and spinophilin as early as 24 h after transfection with APPsw gene. BG45 upregulated the expression of synapse-related proteins and repaired cytoskeletal damage. In vivo, BG45 alleviated the apoptotic loss of hippocampal neurons, upregulated synapse-related proteins, reduced Aβ deposition and phosphorylation of tau and increased the level of the synapse-related genes GRIK2, SCN3B, SYNPR, Grm2, and Grid2IP. BG45 increased the expression of the AMPA receptor subunits GluA1, GluA2 and GluA3 on APPsw-transfected cells and increased GRIP1 and GRIP2 expression and AMPA receptor phosphorylation in vivo. These results suggest that HDACs are involved in the early process of synaptic defects of AD and that BG45 may rescue synaptic damage and loss of hippocampal neurons by specifically inhibiting HDAC1、HDAC2 and HDAC3, thereby modulating AMPA receptor transduction, increasing synapse-related gene expression and finally improving excitatory synapses. BG45 may be considered as a potential drug for the treatment of early AD for further study.

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