scholarly journals Stimulatory Heterotrimeric GTP-binding Protein Inhibits Hydrogen Peroxide-induced Apoptosis by Repressing BAK Induction in SH-SY5Y Human Neuroblastoma Cells

2007 ◽  
Vol 283 (3) ◽  
pp. 1350-1361 ◽  
Author(s):  
So-Young Kim ◽  
MiRan Seo ◽  
Yeni Kim ◽  
Yun-Il Lee ◽  
Jung-Min Oh ◽  
...  
Keyword(s):  
Hydrogen Peroxide ◽  
Cancer Cells ◽  
Neuroblastoma Cells ◽  
Camp Signaling ◽  
Human Neuroblastoma Cells ◽  
Human Neuroblastoma ◽  
Gtp Binding ◽  
Camp Signaling Pathway ◽  
Induced Apoptosis

Heterotrimeric stimulatory GTP-binding protein (Gs) stimulates adenylate cyclases to activate the cAMP signaling pathway. Although the cAMP pathway has been reported to be involved in apoptosis, the role of the Gs-cAMP signaling pathway during reactive oxygen species (ROS)-mediated apoptosis, which is involved in the resistance of cancer cells to chemotherapy and radiation, is not clearly understood. Thus, in this study we aimed to investigate the role of the α subunit of Gs (Gαs) in the ROS-induced apoptosis of cancer cells. The stable expression of constitutively active Gαs (GαsQL) inhibited the hydrogen peroxide-induced apoptosis of SH-SY5Y human neuroblastoma cells and reduced the hydrogen peroxide-induced increase in Bak and the decrease in Bcl-xL protein expression. Exogenous Bak expression abolished these inhibitory effects of GαsQL, but Bak small interfering RNA decreased hydrogen peroxide-induced apoptosis. Gαs repressed hydrogen peroxide-induced Bak expression by inhibiting the transcription of Bak mRNA, which resulted from the inhibition of the hydrogen peroxide-induced activation of transcription factors such as AP1, NF-κB, and NFAT. Moreover, Gαs also inhibited the hydrogen peroxide-induced binding of AP1, NF-κB, and NFAT to the Bak promoter. Furthermore, hydrogen peroxide-induced apoptosis was reduced by treating cells with prostaglandin E2, which activates Gαs, but this was augmented by CCPA, which activates Gαi causing a decrease in cAMP levels. From the results, we conclude that Gαs protects neuroblastoma cells from hydrogen peroxide-induced apoptosis by repressing Bak induction, which is mediated by the inhibition of the hydrogen peroxide-induced activations of AP1, NF-κB, and NFAT through cAMP-PKA-CREB signaling system.

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.

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.

Bax-activation during lidocaine-induced apoptosis in human neuroblastoma cells

2007 ◽  
Vol 32 (Suppl. 1) ◽  
pp. 186
Author(s):  
M. F. Stevens ◽  
S. Braun ◽  
H. Hermanns ◽  
P. Lipfert ◽  
F. Essmann ◽  
...  
Keyword(s):  
Neuroblastoma Cells ◽  
Human Neuroblastoma Cells ◽  
Human Neuroblastoma ◽  
Induced Apoptosis

Lichen Based Synthesis of Zinc Oxide Nanoparticles and Evaluation of its Neurotoxic Effects on Human Neuroblastoma Cells

2019 ◽  
Vol 59 ◽  
pp. 15-24
Author(s):  
Fatih Doğan Koca ◽  
Gökhan Ünal ◽  
Mehmet Gökhan Halici
Keyword(s):  
Hydrogen Peroxide ◽  
Zinc Oxide Nanoparticles ◽  
Neuroblastoma Cells ◽  
Oxide Nanoparticles ◽  
Human Neuroblastoma Cells ◽  
Zno Nps ◽  
Human Neuroblastoma ◽  
Neurotoxic Effects ◽  
Higher Doses ◽  
Scanning Electron

Nanoparticles, smaller than 100 nm are synthesized by chemical and physical methods. Biological synthesis of nanoparticles is very popular in science recently. The aim of the study is green synthesis of zinc oxide nanoparticles (ZnO NPs) using the lichen extract (Ramalina fraxinea) and investigating the cytotoxic effects of ZnO NPs on human neuroblastoma cells (SHSY-5Y). Despite the widespread use of ZnO NPs, a limited number of studies have investigated the neurobiological effects of ZnO NP. Therefore, we tested the neurotoxic effect of green synthesized ZnO NPs administration and its neuroprotective effect against hydrogen peroxide-induced cell damage on SH-SY5Y human neuroblastoma cell line. The absorbance peak of the ZnO NPs was detected by UV–visible spectroscopy (UV-Vis) at 330 nm. The average diameter of ZnO NPs was measured as about 21 nm by Scanning Electron Microscope (SEM) and Field Emission Scanning Electron Microscope (FE-SEM) images. According to X-ray Diffraction (XRD) diagram, ZnO NPs were hexagonal in structure. The peaks observed in the Fourier Transform Infrared (FT-IR) test showed functional groups in the structure of the nanoparticles. According to our results, ZnO NPs may have beneficial effects at the low concentrations while neurotoxic effects at the higher doses in SH-SY5Y. In addition, we indicate that hydrogen peroxide-induced cell death could not reverse by ZnO NPs and its higher doses potentiated the neurodegenerative effect of hydrogen peroxide. In conclusion, here we report that ZnO NPs, widely used in various products, may have beneficial or harmful effects in a dose-dependent manner and play a role in neuropsychiatric disease, especially neurodegenerative diseases. This is the first study dealing with neurotoxicity on SHSY-5Y of Ramalina fraxinea extract based ZnO NPs.

Morroniside Prevents Peroxide-induced Apoptosis by Induction of Endogenous Glutathione in Human Neuroblastoma Cells

2007 ◽  
Vol 28 (2) ◽  
pp. 293-305 ◽  
Author(s):  
Wen Wang ◽  
Wenting Huang ◽  
Lin Li ◽  
Houxi Ai ◽  
Fangling Sun ◽  
...  
Keyword(s):  
Neuroblastoma Cells ◽  
Human Neuroblastoma Cells ◽  
Human Neuroblastoma ◽  
Induced Apoptosis
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