Cadmium Inhibits Neurite Outgrowth in Differentiating Human SH-SY5Y Neuroblastoma Cells

2014 ◽  
Vol 33 (5) ◽  
pp. 412-418 ◽  
Author(s):  
Eun Joo Pak ◽  
Gi Dong Son ◽  
Byung Sun Yoo
Keyword(s):  
Neurite Outgrowth ◽  
Neuroblastoma Cells ◽  
Underlying Mechanism ◽  
Ros Generation ◽  
Dependent Manner ◽  
Cadmium Treatment ◽  
Trans Retinoic Acid ◽  
All Trans Retinoic Acid ◽  
Ros Scavenger ◽  
Dose Dependent

Cadmium, a highly ubiquitous heavy metal, is well known to induce neurotoxicity. However, the underlying mechanism of cadmium-mediated neurotoxicity remains unclear. We have studied cadmium inhibition of neurite outgrowth using human SH-SY5Y neuroblastoma cells induced to differentiate by all- trans-retinoic acid (RA). Cadmium, at a concentration of 3 μmol/L, had no significant effect on the viability of differentiating SH-SY5Y cells. However, the neurite outgrowth of the differentiating SH-SY5Y cells 48 hours after cadmium treatment (1-3 μmol/L cadmium) was significantly inhibited in a dose-dependent manner. Treatment of RA-stimulated differentiating SH-SY5Y cells with 1 to 3 μmol/L cadmium resulted in decreased level of cross-reactivities with 43-kDa growth-associated protein (GAP-43) in a dose-dependent manner. The reactive oxygen species (ROS) scavenger, NAC (N-acetyl-l-cysteine), recovered the expression of GAP-43 in cadmium-treated cells. The results indicate that cadmium is able to inhibit neurite outgrowth of differentiating SH-SY5Y cells and that this effect might result from ROS generation by cadmium.

scholarly journals 9-cis-retinoic acid is a natural antagonist for the retinoic acid receptor response pathway

1993 ◽  
Vol 295 (2) ◽  
pp. 343-346 ◽  
Author(s):  
C Carlberg ◽  
J H Saurat ◽  
G Siegenthaler
Keyword(s):  
Retinoic Acid ◽  
Retinoic Acid Receptor ◽  
Retinoic Acid Receptors ◽  
Dependent Manner ◽  
Receptor Response ◽  
Trans Retinoic Acid ◽  
All Trans Retinoic Acid ◽  
X Receptors ◽  
Dose Dependent

The pleiotropic activities of retinoids are mediated by two types of nuclear receptors, the retinoic acid receptors (RARs) and the retinoid X receptors (RXRs). All-trans-retinoic acid (RA) transcriptionally activates RARs, but not RXRs, whereas its natural stereoisomer, 9-cis-RA, is the ligand for RXRs. Here, we demonstrate that 9-cis-RA did not transcriptionally activate RARs, whereas in the presence of all-trans-RA the transactivation of RARs was inhibited in a dose-dependent manner by 9-cis-RA. RAR homodimer complexes were destabilized in vitro in the presence of 9-cis-RA. This suggests that 9-cis-RA may be a natural antagonist of all-trans-RA for binding to RAR complexes. The levels of 9-cis-RA may determine by which pathway the transcription of retinoid-responsive genes is modulated.

scholarly journals AGE/RAGE-Induced EMP Release via the NOX-Derived ROS Pathway

2018 ◽  
Vol 2018 ◽  
pp. 1-8 ◽  
Author(s):  
Ying-Hua Chen ◽  
Zhang-Wei Chen ◽  
Hong-Mei Li ◽  
Xin-Feng Yan ◽  
Bo Feng
Keyword(s):  
Umbilical Vein ◽  
Underlying Mechanism ◽  
Control Group ◽  
Dependent Manner ◽  
Antioxidant Treatment ◽  
Glycation End Products ◽  
Ros Scavenger ◽  
Umbilical Vein Endothelial Cells ◽  
Dose Dependent

Objective. Diabetes is associated with accelerated formation of advanced glycation end products (AGEs) that are extensively found in circulating endothelial microparticles (EMPs). This study aimed to investigate whether AGEs have a direct effect on EMP formation and the possible underlying mechanism. Methods. In vitro, cultured human umbilical vein endothelial cells (HUVECs) were incubated with AGEs (200 and 400 μg/ml) for 24 hours with or without pretreatment with anti-RAGE antibody, NOX inhibitor, or ROS scavenger. The number of CD31-positive EMPs was assessed by flow cytometry. Results. The number of EMPs was significantly increased in HUVECs stimulated by AGEs in a dose-dependent manner. In addition, receptors for AGEs (RAGE), NAD(P)H oxidase (NOX), and reactive oxygen species (ROS) were increased by AGEs as compared to the control group. These changes could be reversed when HUVECs were pretreated with anti-RAGE antibody. Moreover, inhibition of NOX as well as antioxidant treatment reduced the release of EMPs induced by AGEs. Conclusion. Our study suggested that AGEs increased EMP generation, which was mediated by RAGE signaling through NOX-derived ROS.

Novel azolyl-(phenylmethyl)]aryl/heteroarylamines: Potent CYP26 inhibitors and enhancers of all-trans retinoic acid activity in neuroblastoma cells

2008 ◽  
Vol 16 (17) ◽  
pp. 8301-8313 ◽  
Author(s):  
Mohamed Sayed Gomaa ◽  
Jane L. Armstrong ◽  
Beatrice Bobillon ◽  
Gareth J. Veal ◽  
Andrea Brancale ◽  
...  
Keyword(s):  
Retinoic Acid ◽  
Neuroblastoma Cells ◽  
Trans Retinoic Acid ◽  
All Trans Retinoic Acid

scholarly journals Nonylphenol Induces Apoptosis through ROS/JNK Signaling in a Spermatogonia Cell Line

2020 ◽  
Vol 22 (1) ◽  
pp. 307
Author(s):  
Hyun-Jung Park ◽  
Ran Lee ◽  
Hyunjin Yoo ◽  
Kwonho Hong ◽  
Hyuk Song
Keyword(s):  
Molecular Mechanisms ◽  
Mapk Signaling ◽  
Ros Generation ◽  
Dependent Manner ◽  
Jnk Signaling ◽  
Apoptosis Markers ◽  
Testicular Size ◽  
Spermatogonia Cell ◽  
Induced Apoptosis ◽  
Dose Dependent

Nonylphenol (NP) is an endocrine-disruptor chemical that negatively affects reproductive health. Testes exposure to NP results in testicular structure disruption and a reduction in testicular size and testosterone levels. However, the effects of NP on spermatogonia in testes have not been fully elucidated. In this study, the molecular mechanisms of NP in GC-1 spermatogonia (spg) cells were investigated. We found that cell viability significantly decreased and apoptosis increased in a dose-dependent manner when GC-1 spg cells were exposed to NP. Furthermore, the expression levels of the pro-apoptotic proteins increased, whereas anti-apoptosis markers decreased in NP-exposed GC-1 spg cells. We also found that NP increased reactive oxygen species (ROS) generation, suggesting that ROS-induced activation of the MAPK signaling pathway is the molecular mechanism of NP-induced apoptosis in GC-1 spg cells. Thus, NP could induce c-Jun phosphorylation; dose-dependent expression of JNK, MKK4, p53, and p38; and the subsequent inhibition of ERK1/2 and MEK1/2 phosphorylation. The genes involved in apoptosis and JNK signaling were also upregulated in GC-1 spg cells treated with NP compared to those in the controls. Our findings suggest that NP induces apoptosis through ROS/JNK signaling in GC-1 spg cells.

scholarly journals All-Trans Retinoic Acid Enhances Matrix Metalloproteinase 2 Expression and Secretion in Human Myeloid Leukemia THP-1 Cells

2018 ◽  
Vol 2018 ◽  
pp. 1-10 ◽  
Author(s):  
Hien Thi Vu ◽  
Thi Xoan Hoang ◽  
Jae Young Kim
Keyword(s):  
Retinoic Acid ◽  
Matrix Metalloproteinase ◽  
Calcium Ion ◽  
Myeloid Leukemia ◽  
Leukemia Cell Line ◽  
Matrix Metalloproteinase 2 ◽  
Migration And Invasion ◽  
Dependent Manner ◽  
Trans Retinoic Acid ◽  
All Trans Retinoic Acid

All-trans retinoic acid (ATRA) is an effective drug for the induction therapy of acute promyelocytic leukemia. However, the treatment is associated with adverse events such as retinoic acid syndrome (RAS) in some patients, whose histologic characteristics included organ infiltration by leukemic cells. Matrix metalloproteinase 2 (MMP-2) is often upregulated in tumor cells and plays a role in tumor cell migration and invasion by degrading the extracellular matrix. In this study, we examined the possible modulatory effects of ATRA on MMP-2 expression and secretion in human myeloid leukemia cell line THP-1. The cells were treated with various concentrations of ATRA, and MMP-2 expression and secretion were examined. MMP-2 expression and secretion started to increase with ATRA concentration as low as 0.1 nM and gradually increased thereafter. Agonists of retinoic acid receptor (RAR) or retinoid X receptor (RXR) alone could enhance MMP-2 secretion, and RAR or RXR antagonists alone could reverse ATRA-induced MMP-2 secretion. ATRA increased intracellular calcium ion levels, and a calcium-channel blocker inhibited ATRA-induced MMP-2 secretion. Dexamethasone suppressed ATRA-induced MMP-2 secretion. Our results suggest that ATRA enhances MMP-2 expression and secretion in human myeloid leukemia THP-1 cells in a calcium ion dependent manner through RAR/RXR signaling pathways, and this enhanced expression and secretion may be associated with the possible mechanisms of RAS.

scholarly journals Apamin Enhances Neurite Outgrowth and Regeneration after Laceration Injury in Cortical Neurons

Toxins ◽  
2021 ◽  
Vol 13 (9) ◽  
pp. 603
Author(s):  
Hyunseong Kim ◽  
Jin Young Hong ◽  
Junseon Lee ◽  
Wan-Jin Jeon ◽  
In-Hyuk Ha
Keyword(s):  
Phospholipase A2 ◽  
Neurite Outgrowth ◽  
Cortical Neurons ◽  
Neurological Diseases ◽  
Minor Component ◽  
Underlying Mechanism ◽  
Bee Venom ◽  
Dependent Manner ◽  
Neuroprotective Effects ◽  
Wide Range

Apamin is a minor component of bee venom and is a polypeptide with 18 amino acid residues. Although apamin is considered a neurotoxic compound that blocks the potassium channel, its neuroprotective effects on neurons have been recently reported. However, there is little information about the underlying mechanism and very little is known regarding the toxicological characterization of other compounds in bee venom. Here, cultured mature cortical neurons were treated with bee venom components, including apamin, phospholipase A2, and the main component, melittin. Melittin and phospholipase A2 from bee venom caused a neurotoxic effect in dose-dependent manner, but apamin did not induce neurotoxicity in mature cortical neurons in doses of up to 10 µg/mL. Next, 1 and 10 µg/mL of apamin were applied to cultivate mature cortical neurons. Apamin accelerated neurite outgrowth and axon regeneration after laceration injury. Furthermore, apamin induced the upregulation of brain-derived neurotrophic factor and neurotrophin nerve growth factor, as well as regeneration-associated gene expression in mature cortical neurons. Due to its neurotherapeutic effects, apamin may be a promising candidate for the treatment of a wide range of neurological diseases.

scholarly journals Caffeic Acid Induced Apoptosis in MG63 Osteosarcoma Cells Through Activation of Caspases

2017 ◽  
Vol 1 (1) ◽  
pp. 28
Author(s):  
Ferry Sandra ◽  
Meta Ariyani Sidharta
Keyword(s):  
Caffeic Acid ◽  
Caspase 8 ◽  
Dependent Manner ◽  
Osteosarcoma Cells ◽  
Concentration Dependent Manner ◽  
Trans Retinoic Acid ◽  
All Trans Retinoic Acid ◽  
Proliferation Activity ◽  
Fetal Bovine ◽  
Induced Apoptosis

Background: Caffeic acid has been reported that when it is combined with all-trans retinoic acid, it can inhibit proliferation activity of SaOS-2 or OSA-01 cells. In addition, caffeic acid merely could reduce cell viability of SaOS-2 cells. However, there is not any study in caffeic acid's possible effect to induce apoptosis in osteosarcoma cell.Materials and Methods: MG-63 cells were cultured in Dulbecco’s Modified Eagle Medium containing 10% fetal bovine serum. Cells were treated with various concentrations of caffeic acid. Apoptosis were analyzed with Sub-G1 assay and activation of caspase-8, -9, and -3 were analyzed with immunoblotting. Caffeic acid-induced percentage of apoptotic cells and cleaved-8, -9, -3 were then statistically analyzed.Results: Sub-G1 results showed that caffeic acid significantly induced apoptosis in MG-63 osteosarcoma cells in concentration dependent manner. Immunoblotting results showed that caffeic acid induced cleavage of caspase-8, -9 and -3. Cleaved-caspase-8 and -9 were increased at 1-hour treatment of caffeic acid, while cleaved-caspase 3 was increased markedly at 6-hours treatment of caffeic acid.Conclusions: Caffeic acid induces apoptosis significantly in concentration dependent manner through caspase-dependent intrinsic apoptotic pathway.Keywords: caffeic acid, osteosarcoma, MG-63, apoptosis, caspase

scholarly journals All-Trans Retinoic Acid induces synaptic plasticity in human cortical neurons

2020 ◽  
Author(s):  
Maximilian Lenz ◽  
Pia Kruse ◽  
Amelie Eichler ◽  
Julia Muellerleile ◽  
Jakob Straehle ◽  
...  
Keyword(s):  
Retinoic Acid ◽  
Synaptic Plasticity ◽  
Cortical Neurons ◽  
Mrna Translation ◽  
Dependent Manner ◽  
Human Cortex ◽  
Functional Changes ◽  
Trans Retinoic Acid ◽  
All Trans Retinoic Acid ◽  
Structural And Functional Properties

ABSTRACTA defining feature of the brain is its ability to adapt structural and functional properties of synaptic contacts in an experience-dependent manner. In the human cortex direct experimental evidence for synaptic plasticity is currently missing. Here, we probed plasticity in human cortical slices using the vitamin A derivative all-trans retinoic acid, which has been suggested as medication for the treatment of neuropsychiatric disorders, e.g., Alzheimer’s disease. Our experiments demonstrate coordinated structural and functional changes of excitatory synapses of superficial (layer 2/3) pyramidal neurons in the presence of all-trans retinoic acid. This synaptic adaptation is accompanied by ultrastructural remodeling of the calcium-storing spine apparatus organelle and requires mRNA-translation. We conclude that all-trans retinoic acid is a potent mediator of synaptic plasticity in the adult human cortex.

scholarly journals Triterpenoid Saponin AG8 from Ardisia gigantifolia stapf. Induces Triple Negative Breast Cancer Cells Apoptosis through Oxidative Stress Pathway

2020 ◽  
Vol 2020 ◽  
pp. 1-11
Author(s):  
Li-Hua Mu ◽  
Li-Hua Wang ◽  
Teng-Fei Yu ◽  
Yu-Ning Wang ◽  
Hong Yan ◽  
...  
Keyword(s):  
Triple Negative ◽  
Growth Factor Receptor ◽  
Cell Types ◽  
Ros Generation ◽  
Triterpenoid Saponin ◽  
Dependent Manner ◽  
Breast Cancers ◽  
Underlying Mechanisms ◽  
Apoptotic Pathways ◽  
Dose Dependent

Triple-negative breast cancers (TNBCs) are associated with poor patient survival because of the absence of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) expressions. Our previous studies have shown that the triterpenoid saponin AG8 from Ardisia gigantifolia stapf. inhibits the proliferation of MDA-MB-231 cells. In this study, the effects of AG8 were further analyzed in different TNBC cell types: MDA-MB-231, BT-549, and MDA-MB-157 cells. AG8 inhibited the viability of MDA-MB-231, BT-549, and MDA-MB-157 cells in a dose-dependent manner and showed stronger cytotoxicity to African American (AA) and mesenchymal (M) subtypes than Caucasian (CA) and mesenchymal stem-like (MSL) subtypes, respectively. AG8 impaired the uptake of MitoTracker Red CMXRos by the mitochondria of TNBC cells in a dose-dependent manner, and this was recovered by N-acetyl-l-cysteine (NAC). AG8 affected GSH, SOD, and MDA levels of TNBC cells, but different TNBC subtypes had different sensitivities to AG8 and NAC. In addition, we found that AG8 increased the Bax/Bcl-2 ratio and the levels of cytoplasmic cytochrome c and significantly decreased phosphorylation of ERK and AKT in BT549 and MDA-MB-157 cells. AG8 elicited its anticancer effects through ROS generation, ERK and AKT activation, and by triggering mitochondrial apoptotic pathways in TNBC cells. AG8 had selective cytotoxic effects against the AA and M TNBC subtypes and markedly induced MDA-MB-157 (AA subtype) cell apoptosis through pathways that were not associated with ROS, which was different from the other two subtypes. The underlying mechanisms should be further investigated.

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