The Nrf2 Signaling in Retinal Ganglion Cells under Oxidative Stress in Ocular Neurodegenerative Diseases

Liu, Xiufen; Zhou, Dandan; Xie, Tian; Hao, Ji‐Long; Malik, Tayyab Hamid; Lu, Cheng-Bo; Qi, Jing; Pant, Om Prakash; Lu, Cheng‐Wei

doi:10.7150/ijbs.25996

Cited by 59 publications

(46 citation statements)

References 89 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Then, transcription of antioxidant enzymes and phase II detoxification enzymes occurs, including heme oxygenase-1 (HO-1), NAD(P)H: quinone oxidoreductase 1 (NQO1) [17]. Also, g-glutamyl cysteine ligase catalytic subunit (GCLC), glutathione peroxidase [13], glutathione-S-transferase (GST), catalase, superoxide dismutase, and thioredoxin uridine 5'-diphospho-glucuronosyltransferase) (UDP)-glucuronosyltransferase occurs [18][19][20][21]. However, Nrf2 may be dissociated from the cytoplasmic Nrf2-keap1-cul3 complex by p62, which is a marker of cell autophagy [22].…”

Section: Introductionmentioning

confidence: 99%

The Potential Role of Nuclear Factor Erythroid 2-Related Factor 2 (Nrf2) in Glaucoma: A Review

Wang

Zheng

2020

Med Sci Monit

View full text Add to dashboard Cite

Departmental sources Nuclear factor erythroid 2-related factor 2 (Nrf2) acts as a regulator of many biological processes and plays an essential role in preventing oxidation, inflammation, and fibrosis. In the past 20 years, there has been increasing research on the role of Nrf2 and oxidative stress in human glaucoma, including the roles of inflammation, trabecular meshwork cells, retinal ganglion cells, Tenon's capsule, antioxidants, fibrosis, and noncoding RNAs. Studies have shown that the upregulation of Nrf2 can reduce damage from oxidative stress in the trabecular meshwork cells and the retinal ganglion cells, reduce fibrosis in Tenon's capsule fibroblasts, which may reduce the progression of fibrosis after surgery for glaucoma. The regulatory roles of Nrf2, microRNAs (miRNAs), long noncoding RNAs (lncRNAs), and exogenous compounds on trabecular meshwork cells (TMCs) and retinal ganglion cells have also been studied. The use of Nrf2 agonists, including noncoding RNAs, control the expression of Nrf2 through signaling pathways that continue to be investigated to identify effective treatments to improve clinical outcome following surgery for glaucoma. This review of publications between 1999 and 2019 aims to focus on the potential mechanisms of Nrf2 in the occurrence and development of glaucoma and the prognosis following surgical treatment. Also, several factors that induce the expression of Nrf2 in trabecular meshwork cells, retinal ganglion cells, and human Tenon's capsule fibroblasts are discussed.

show abstract

Section: Introductionmentioning

confidence: 99%

The Potential Role of Nuclear Factor Erythroid 2-Related Factor 2 (Nrf2) in Glaucoma: A Review

Wang

Zheng

2020

Med Sci Monit

View full text Add to dashboard Cite

show abstract

“…Nuclear factor erythroid 2‐related factor 2 (Nrf2) is an important transcription factor that regulates cellular antioxidant activity and has been shown to protect organs in several animal models . Nrf2–mediated antioxidant gene expression can reduce the macrophage M1 phenotype and ROS production; therefore, activating the Nrf2 pathway may inhibit the progression of inflammation and may be a potential therapeutic strategy for many disorders such as cardiovascular diseases, neurodegenerative diseases and multiple sclerosis . Moreover, Nrf2 has been reported to be an important regulator in protecting against TBI–induced secondary brain injury.…”

Section: Introductionmentioning

confidence: 99%

Dexmedetomidine Attenuates Neuroinflammatory–Induced Apoptosis after Traumatic Brain Injury via Nrf2 signaling pathway

Xiao-dong

Zhang

et al. 2019

Ann Clin Transl Neurol

View full text Add to dashboard Cite

Objective Dexmedetomidine (DEX) exhibits neuroprotective effects as a multifunctional neuroprotective agent in numerous neurological disorders. However, in traumatic brain injury (TBI), the molecular mechanisms of these neuroprotective effects remain unclear. The present study investigated whether DEX, which has been reported to exert protective effects against TBI, could attenuate neuroinflammatory‐induced apoptosis and clarified the underlying mechanisms. Methods A weight‐drop model was established, and DEX was intraperitoneally injected 30 min after inducing TBI in rats. The water content in the brain tissue was measured. Terminal deoxynucleotidyl transferase‐mediated dUTP nick‐end labeling (TUNEL) assays were performed on histopathological tissue sections to evaluate neuronal apoptosis. Enzyme‐linked immunosorbent assay and PCR were applied to detect the levels of the inflammatory factors, TNF‐α, IL‐1β, IL‐6, and NF‐κB. Results TBI–challenged rats exhibited significant neuronal apoptosis, which was characterized via the wet‐to‐dry weight ratio, neurobehavioral functions, TUNEL assay results and the levels of cleaved caspase‐3, Bax upregulation and Bcl‐2, which were attenuated by DEX. Western blot, immunohistochemistry, and PCR results revealed that DEX promoted Nrf2 expression and upregulated expression of the Nrf2 downstream factors, HO‐1 and NQO‐1. Furthermore, DEX treatment markedly prevented the downregulation of inflammatory response factors, TNF‐α, IL‐1β and NF‐κB, and IL‐6. Interpretation Administering DEX attenuated inflammation‐induced brain injury in a TBI model, potentially via the Nrf2 signaling pathway.

show abstract

“…The current study confirmed that an APAP and ROX co-treatment increased the MDA level and depressed GPX and SOD activities ( Figure 5), suggesting the impairment of hepatic redox homeostasis, accumulation of ROS and formation of lipid peroxidation. Co-treatment significantly increased the mRNA expression of Nrf2 (Figure 6), which is significant because the activated Nrf2 is a transcription factor that modulates endogenous antioxidant enzymes [18,19]. APAP and ROX stimulate Nrf2 activation, which binds to the antioxidant response element and further activates the transcription of gene-encoding for antioxidants and detoxification, including haem oxygenase-1 (HO-1), NADPH, quinone oxidoreductase-1 (NQO-1) and glutathione-synthesising enzymes glutamatecysteine ligase catalytic subunit (GCLC).…”

Section: Discussionmentioning

confidence: 96%

Drug-drug interaction of acetaminophen and roxithromycin with the cocktail of cytochrome P450 and hepatotoxicity in rats

2020

View full text Add to dashboard Cite

Acetaminophen (APAP) and roxithromycin (ROX) are often used in combination in clinical practice. To evaluate their drug-drug interactions (DDIs) and the hepatotoxicity of co-administration, rats were randomly separated into four groups: Control, APAP (50 mg/kg), ROX (5.5 mg/kg) and APAP-ROX (50 mg/kg and 5.5 mg/kg, respectively). The pharmacokinetic parameters between APAP and ROX were assayed by HPLC, and a cocktail method was used to evaluate the activities of cytochrome (CYP) 450. The liver microsome CYP2E1 protein was detected using Western blot. The levels of plasma parameters, mRNA levels of inflammatory factors (TNF-α, INF-γ, VCAM-1, CXCL-1 and STAT-3) and antioxidant factors (Nrf-2, GSTA, GCLC-1, HO-1 and NQO1) were determined using real-time PCR, along with the observation on histopathological changes in the liver tissue. APAP and ROX co-treatment significantly increased CYP2E1 activity, decreased CYP2D6 activity and prolonged APAP and ROX clearance. Co-treatment increased mRNA expressions of TNF-α, NQO1 and MDA while decreasing GPX and SOD levels. Histopathological evidence showed the changes of liver tissues in terms of structure, size and tight arrangement. This study confirmed that a combination of APAP and ROX inhibited APAP metabolism and that the peak concentration of ROX was delayed. The resulting high level of CYP2E1 may induce oxidative stress and cause liver damage.

show abstract

The Nrf2 Signaling in Retinal Ganglion Cells under Oxidative Stress in Ocular Neurodegenerative Diseases

Cited by 59 publications

References 89 publications

The Potential Role of Nuclear Factor Erythroid 2-Related Factor 2 (Nrf2) in Glaucoma: A Review

The Potential Role of Nuclear Factor Erythroid 2-Related Factor 2 (Nrf2) in Glaucoma: A Review

Dexmedetomidine Attenuates Neuroinflammatory–Induced Apoptosis after Traumatic Brain Injury via Nrf2 signaling pathway

Drug-drug interaction of acetaminophen and roxithromycin with the cocktail of cytochrome P450 and hepatotoxicity in rats

Contact Info

Product

Resources

About