UCH-L1 mitigates neurotoxicity induced by ZnO particles via stabilizing the inhibitor of NF-kappa B signaling, IκB-α.

08:00 EDT 13th May 2019 | BioPortfolio

Summary of "UCH-L1 mitigates neurotoxicity induced by ZnO particles via stabilizing the inhibitor of NF-kappa B signaling, IκB-α."

Our study determined the toxic effects of zinc oxide (ZnO) particles with different diameters on dopaminergic (DA) neurons, the role of ubiquitin C-terminal hydrolase L1 (UCH-L1) for ZnO particles-induced neurotoxicity, and corresponding molecular mechanisms. We constructed an in vitro cell injury model for DA neurons to analyze the cytotoxicity of ZnO particles using SH-SY5Y cells. Following cell viability assays and flow cytometry, we found that the cytotoxicity of ZnO particles was affected by particle size, time, and dose of exposure. For example, the toxicity of ZnO particles with 50 nm or 100 nm diameter was stronger than that of ZnO particles with 1000 nm diameter. Furthermore, ZnO particles exposure resulted in a significant decrease in UCH-L1 expression in SH-SY5Y; whereas UCH-L1 overexpression led to a significant increase in cell viability and a sharp decrease in ROS level. Western blotting and adenovirus transfection found that exposure to ZnO particles with different diameters all activate the NF-κB signaling in SH-SY5Y cells; whereas UCH-L1 over-expression resulted in increased levels of IκBα, an endogenous inhibitor of NF-κB signaling pathway. ZnO particles with different diameters all induced cytotoxicity in DA neurons, which may be related to the free Zn in the suspension. Regarding the neurotoxic effect of ZnO particles, UCH-L1 protects against and/or alleviates neuronal damage, possibly by deubiquitination of the endogenous inhibitor, IκBα, which leads to activation of NF-κB signaling. Therefore, one possible mechanism for ZnO particle-induced neurotoxicity may be mediated via the down-regulation of UCH-L1 expression in DA cells.


Journal Details

This article was published in the following journal.

Name: Ecotoxicology and environmental safety
ISSN: 1090-2414
Pages: 259-268


DeepDyve research library

PubMed Articles [18641 Associated PubMed Articles listed on BioPortfolio]

Hydrogen Sulfide Inhibits Formaldehyde-Induced Senescence in HT-22 Cells via Upregulation of Leptin Signaling.

It has been previously demonstrated that hydrogen sulfide (HS) prevents formaldehyde (FA)-induced neurotoxicity. However, the exact mechanisms underlying this protection remain to be fully elucidated....

Dexmedetomidine protects against lipopolysaccharide-induced early acute kidney injury by inhibiting the iNOS/NO signaling pathway in rats.

Increasing evidence has demonstrated that dexmedetomidine (DEX) possesses multiple pharmacological actions. Herein, we explored the protective effect and potential molecular mechanism of DEX on lipopo...

Thymosin beta 4-Induced Autophagy Increases Cholinergic Signaling in PrP (106-126)-Treated HT22 Cells.

Prion protein peptide (PrP) has been associated with neurotoxicity in brain cells and progression of prion diseases due to spongiform degeneration and accumulation of the infectious scrapie prion prot...

Neurotoxicity of anesthetics: Mechanisms and meaning from mouse intervention studies.

Volatile anesthetics are widely used in human medicine and generally considered to be safe in healthy individuals. In recent years, the safety of volatile anesthesia in pediatric patients has been que...

Mechanistic Interplay between Autophagy and Apoptotic Signaling in Endosulfan-induced Dopaminergic Neurotoxicity: Relevance to the Adverse Outcome Pathway in Pesticide Neurotoxicity.

Chronic exposure to pesticides is implicated in the etiopathogenesis of Parkinson's disease (PD). Previously, we showed that dieldrin induces dopaminergic neurotoxicity by activating a cascade of apop...

Clinical Trials [5854 Associated Clinical Trials listed on BioPortfolio]

Evaluate the Neuroprotective Effect of Vitamin B6 and Vitamin B12 Against Vincristine Induced Neurotoxicity in Acute Lymphoblastic Leukaemia Patients

This study will be conducted to evaluate the effect of vitamin B6 and vitamin B12 in reducing the incidence and severity and delaying the onset of Vincristine Induced neurotoxicity in Acut...

To Study the Individual Variants of Chemotherapy-Induced Neurotoxicity

To study the risk prediction of chemotherapy-induced peripheral neuropathy (CIPN) by the clinical bioinformatics and genomic profile.

Monosialoganglioside Preventing Neurotoxicity Induced by Albumin-bound Paclitaxel Chemotherapy in Lung Cancer Patients

The purpose of this study is to determine whether monosialoganglioside are effective in the prevention of neurotoxicity induced by albumin-bound paclitaxel chemotherapy in lung cancer pati...

The Neuroprotective Effects of Dexmedetomidine During Brain Surgery

Dexmedetomidine (DEX) is a Alpha-2 specific agonist, is a common ICU sedation medication. In brain tumor resection craniotomy, it is proven to be effective in improving postoperative hyper...

Analysis of Induced Sputum and Lung Biopsies by SEM: a Tool to Identify Source of Exposure of Workers to Hazardous Dust

Aim : to validate the qualitative analysis by Scanning Electron Microscope (SEM) of lung samples first in induced sputum in correlation to disease second by comparing hazardous particles...

Medical and Biotech [MESH] Definitions

An I-kappa B protein that inhibits the activity of dimeric NF-KAPPA B P50-REL complexes, sequesters transcription factor NF-kappaB as an inactive complex in the cytoplasm; and prevents NF-kappaB nuclear translocation and DNA binding.

A family of inhibitory proteins which bind to the REL PROTO-ONCOGENE PROTEINS and modulate their activity. In the CYTOPLASM, I-kappa B proteins bind to the transcription factor NF-KAPPA B. Cell stimulation causes its dissociation and translocation of active NF-kappa B to the nucleus.

A component of NF-kappa B transcription factor. It is proteolytically processed from NF-kappa B p100 precursor protein and is important for maturation of B-LYMPHOCYTES and adaptive HUMORAL IMMUNITY.

A widely expressed member of the TNF receptor-associated family that may play a role in neuronal development and EMBRYOGENESIS. Although TNF receptor-associated factor 4 does not strongly associate with TUMOR NECROSIS FACTOR RECEPTORS it may be a signaling partner with the GLUCOCORTICOID-INDUCED TNFR-RELATED PROTEIN that plays a role in the activation of JNK MITOGEN-ACTIVATED PROTEIN KINASES and NF-KAPPA B.

Ubiquitous, inducible, nuclear transcriptional activator that binds to enhancer elements in many different cell types and is activated by pathogenic stimuli. The NF-kappa B complex is a heterodimer composed of two DNA-binding subunits: NF-kappa B1 and relA.

Quick Search


DeepDyve research library

Relevant Topic

Immunoassay - ELISA
Immunoassays are quick and accurate tests to detect specific molecules. Immunoassays rely on an antibody to bind to the specific structure of a molecule. Antibodies are proteins generated by animals in response to the invasion of a foreign molecule (anti...

Searches Linking to this Article