scholarly journals Nrf2, a Potential Therapeutic Target against Oxidative Stress in Corneal Diseases

2017 ◽  
Vol 2017 ◽  
pp. 1-9 ◽  
Author(s):  
Xiu-Fen Liu ◽  
Dan-Dan Zhou ◽  
Tian Xie ◽  
Tayyab Hamid Malik ◽  
Cheng-Bo Lu ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Therapeutic Target ◽  
Expression Profiles ◽  
Corneal Dystrophy ◽  
Antioxidant Response ◽  
Erythroid Cell ◽  
Defense Systems ◽  
Promising Therapeutic Target ◽  
Corneal Wound ◽  
Underlying Mechanisms

Corneal diseases are one of the major causes of blindness worldwide. Conservative medical agents, which may prevent sight-threatening corneal disease progression, are urgently desired. Numerous evidences have revealed the involvement of oxidative stress in various corneal diseases, such as corneal wound healing and Fuchs endothelial corneal dystrophy (FECD). Nuclear factor (erythroid-derived 2)-like 2 (Nrf2)/Kelch-like erythroid-cell-derived protein with CNC homology- (ECH-) associated protein 1 (Keap1)/antioxidant response element (ARE) signaling is well known as one of the main antioxidative defense systems. To the best of our knowledge, this is the first review to elucidate the different expression profiles of Nrf2 signaling as well as the underlying mechanisms in corneal diseases, implicating that Nrf2 may serve as a potentially promising therapeutic target for corneal diseases.

scholarly journals FOXO1, a Potential Therapeutic Target, Regulates Autophagic Flux, Oxidative Stress, Mitochondrial Dysfunction, and Apoptosis in Human Cholangiocarcinoma QBC939 Cells

2018 ◽  
Vol 45 (4) ◽  
pp. 1506-1514 ◽  
Author(s):  
Wei He ◽  
Aiqing Zhang ◽  
Lei Qi ◽  
Chen Na ◽  
Rui Jiang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Mitochondrial Dysfunction ◽  
Therapeutic Target ◽  
Energy Homeostasis ◽  
Serum Starvation ◽  
Autophagic Flux ◽  
Potential Therapeutic Target ◽  
New Strategy ◽  
Underlying Mechanisms ◽  
Foxo1 Gene

Background/Aims: Autophagy is an evolutionarily conserved catabolic mechanism to maintain energy homeostasis and to remove damaged cellular components, which plays an important role in the survival of various cells. Inhibiting autophagy is often applied as a new strategy to halt the growth of cancer cells. Methods: The effect of FOXO1 gene on cellular function and apoptosis and its underlying mechanisms were investigated in cultured QBC939 cells by the methylthiazoletetrazolium (MTT) assay, western blot, DCFDA mitochondrial membrane potential, and ATP content measurement. FOXO1 siRNA was applied to down-regulate FOXO1 expression in QBC939 cells. Results: Here we reported that FOXO1, acetylation of FOXO1 (Ac-FOXO1) and the following interaction between Ac-FOXO1 and Atg7 regulated the basal and serum starvation (SS)-induced autophagy as evidenced by light chain 3 (LC3) accumulation and p62 degration. Either treatment with FOXO1 siRNA or resveratrol, a sirt1 agonist, inhibited autophagic flux, resulting in oxidative stress, mitochondrial dysfunction (MtD) and apoptosis in QBC939 cells, which were attenuated by enhancing autophagy with rapamycin. On the contrary, inhibiting autophagic flux with 3-MA worsened all these effects in QBC939 cells. Conclusions: Taken together, our study for the first time identified FOXO1 as a potential therapeutic target to cure against human cholangiocarcinoma via regulation of autophagy, oxidative stress and MtD.

scholarly journals Epigenetic Modifier SETD8 as a Therapeutic Target for High-Grade Serous Ovarian Cancer

Biomolecules ◽  
2020 ◽  
Vol 10 (12) ◽  
pp. 1686
Author(s):  
Miku Wada ◽  
Asako Kukita ◽  
Kenbun Sone ◽  
Ryuji Hamamoto ◽  
Syuzo Kaneko ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cell Proliferation ◽  
Therapeutic Target ◽  
Expression Profiles ◽  
High Grade ◽  
Histone H4 ◽  
Nonhistone Proteins ◽  
Functional Studies ◽  
Promising Therapeutic Target ◽  
Interfering Rna

The histone methyltransferase SETD8, which methylates the lysine 20 of histone H4 (H4K20), is reportedly involved in human carcinogenesis along with nonhistone proteins such as p53. However, its expression profiles and functions in the context of high-grade serous ovarian carcinoma (HGSOC) are still unknown. The purpose of this study was to investigate the role of SETD8 in HGSOC. We performed quantitative real-time PCR and immunohistochemistry to detect the expression of SETD8 in HGSOC samples and normal ovarian specimens. Then, we assessed the effect of the inhibition of SETD8 expression using small interfering RNA (siRNA) and a selective inhibitor (UNC0379) on cell proliferation and apoptosis in HGSOC cells. The expression of SETD8 was significantly upregulated in clinical ovarian cancer specimens compared to that in the corresponding normal ovary. In addition, suppression of SETD8 expression in HGSOC cells with either siRNA or UNC0379 resulted in reduced levels of H4K20 monomethylation, inhibition of cell proliferation, and induction of apoptosis. Furthermore, UNC0379 showed a long-term antitumor effect against HGSOC cells, as demonstrated by colony-formation assays. SETD8 thus constitutes a promising therapeutic target for HGSOC, warranting further functional studies.

scholarly journals BNIP3 phosphorylation by JNK1/2 promotes mitophagy via enhancing its stability under hypoxia

2020 ◽  
Author(s):  
Yun-Ling He ◽  
Sheng-Hui Gong ◽  
Xiang Cheng ◽  
Ming Zhao ◽  
Tong Zhao ◽  
...  
Keyword(s):  
Membrane Protein ◽  
Outer Membrane Protein ◽  
Therapeutic Target ◽  
Proteasomal Degradation ◽  
Mitochondrial Outer Membrane ◽  
Hypoxic Conditions ◽  
Promising Therapeutic Target ◽  
Direct Binding ◽  
Metabolic Mechanism ◽  
Underlying Mechanisms

AbstractMitophagy is an important metabolic mechanism that modulates mitochondrial quality and quantity by selectively removing damaged or unwanted mitochondria. BNIP3, a mitochondrial outer membrane protein, is a mitophagy receptor that mediates mitophagy under various stresses, particularly hypoxia, since BNIP3 is a hypoxia-responsive protein. However, the underlying mechanisms that regulate BNIP3 and thus mediate mitophagy under hypoxic conditions remain elusive. Here, we demonstrate that in hypoxia JNK1/2 phosphorylates BNIP3 at Ser 60/Thr 66, which hampers proteasomal degradation of BNIP3 and drives mitophagy by facilitating the direct binding of BNIP3 to LC3, while PP1/2A represses mitophagy by dephosphorylating BNIP3 and triggering its proteasomal degradation. These findings reveal the intrinsic mechanisms cells use to regulate mitophagy via the JNK1/2-BNIP3 pathway in response to hypoxia. Thus, the JNK1/2-BNIP3 signaling pathway strongly links mitophagy to hypoxia and may be a promising therapeutic target for hypoxia-related diseases.

scholarly journals S-ketamine alleviates carbon tetrachloride-induced hepatic injury and oxidative stress by targeting the Nrf2/HO-1 signaling pathway

2021 ◽  
Author(s):  
Weimin Xu ◽  
Peng Wang ◽  
Dalong Wang ◽  
Ke Liu ◽  
Shuaishuai Zhang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Carbon Tetrachloride ◽  
Signaling Pathway ◽  
Cell Apoptosis ◽  
Biochemical Parameters ◽  
Antioxidant Response ◽  
Histopathological Analysis ◽  
Underlying Mechanisms ◽  
Related Proteins ◽  
And Oxidative Stress

The aim of the present study was to investigate the protective effect of S-ketamine (S-KET) against carbon tetrachloride (CCl4)-induced liver damage and oxidative stress, as well as to elucidate the related underlying mechanisms. Blood was collected to measure biochemical parameters (ALT, AST, ALP, TB and γ-GT) and the liver was harvested for histopathological analysis of enzymes related to the antioxidant response (MDA, SOD, GSH, and GSH-PX). Liver cell apoptosis was evaluated using the TUNEL assay. In addition, the expression levels of apoptosis-related proteins and the Nrf2/HO-1 signaling pathway were detected by western blot analysis to explore potential mechanisms. S-KET protected the liver from CCl4-induced damage. The changes to the liver biochemical parameters (increased ALT, AST, ALP, TB, and γ-GT) and oxidative stress-related indicators (increased MDA; depleted SOD, GSH, and GSH-PX) induced by CCl4 were inhibited by S-KET. S-KET also inhibited CCl4-induced cell apoptosis, the changes in expression of related proteins, and blocked CCl4-induced liver injury and oxidative stress via activation of the Nrf2/HO-1 signaling pathway. S-KET effectively protected the liver by inhibition of CCl4-induced damage via up-regulation the Nrf2/HO-1 signaling pathway.

Nrf2—a Promising Therapeutic Target for Defensing Against Oxidative Stress in Stroke

2016 ◽  
Vol 54 (8) ◽  
pp. 6006-6017 ◽  
Author(s):  
Rongrong Zhang ◽  
Mengxue Xu ◽  
Yu Wang ◽  
Fei Xie ◽  
Gang Zhang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Therapeutic Target ◽  
Promising Therapeutic Target

scholarly journals NLRP3 Inflammasome: A Promising Therapeutic Target for Drug-Induced Toxicity

2021 ◽  
Vol 9 ◽  
Author(s):  
Shanshan Wei ◽  
Wanjun Ma ◽  
Bikui Zhang ◽  
Wenqun Li
Keyword(s):  
Nlrp3 Inflammasome ◽  
Therapeutic Target ◽  
Pathological Process ◽  
Protective Effects ◽  
Drug Induced ◽  
Human Organ ◽  
Pyrin Domain ◽  
Promising Therapeutic Target ◽  
Underlying Mechanisms ◽  
External Stimuli

Drug-induced toxicity, which impairs human organ function, is a serious problem during drug development that hinders the clinical use of many marketed drugs, and the underlying mechanisms are complicated. As a sensor of infections and external stimuli, nucleotide-binding oligomerization domain (NOD)-like receptor family pyrin domain containing 3 (NLRP3) inflammasome plays a key role in the pathological process of various diseases. In this review, we specifically focused on the role of NLRP3 inflammasome in drug-induced diverse organ toxicities, especially the hepatotoxicity, nephrotoxicity, and cardiotoxicity. NLRP3 inflammasome is involved in the initiation and deterioration of drug-induced toxicity through multiple signaling pathways. Therapeutic strategies via inhibiting NLRP3 inflammasome for drug-induced toxicity have made significant progress, especially in the protective effects of the phytochemicals. Growing evidence collected in this review indicates that NLRP3 is a promising therapeutic target for drug-induced toxicity.

scholarly journals MicroRNA-200b-3p promotes endothelial cell apoptosis by targeting HDAC4 in atherosclerosis

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Fan Zhang ◽  
Naixuan Cheng ◽  
Jie Du ◽  
Haibo Zhang ◽  
Congcong Zhang
Keyword(s):  
Oxidative Stress ◽  
Endothelial Cells ◽  
Coronary Arteries ◽  
Coronary Atherosclerosis ◽  
Expression Profiles ◽  
Family Members ◽  
Annexin V ◽  
Differentially Expressed ◽  
Expression Levels ◽  
Promising Therapeutic Target

Abstract Background Epicardial adipose tissue (EAT) shares the same microcirculation with coronary arteries through coronary arteries branches, and contributes to the development of atherosclerosis. MicroRNAs (miRNAs) are involved in the formation of atherosclerosis. However, the alteration of miRNA profile in EAT during atherosclerosis is still uncovered. Methods The miRNA expression profiles of EAT from non-coronary atherosclerosis disease (CON, n = 3) and coronary atherosclerosis disease (CAD, n = 5) patients was performed to detect the differentially expressed miRNA. Then the expression levels of miRNA in other CON (n = 5) and CAD (n = 16) samples were confirmed by realtime-PCR. miR-200b-3p mimic was used to overexpress the miRNA in HUVECs. The apoptosis of HUVECs cells was induced by H2O2 and ox-LDL, and detected by Annexin V/PI Staining, Caspase 3/7 activity and the expression of BCL-2 and BAX. Results 250 miRNAs were differentially expressed in EAT from CAD patients, which were associated with metabolism, extracellular matrix and inflammation process. Among the top 20 up-regulated miRNAs, the expression levels of miR-200 family members (hsa-miR-200b/c-3p, miR-141-3p and miR-429), which were rich in endothelial cells, were increased in EAT from CAD patients significantly. Upregulation of miR-200 family members was dependent on the oxidative stress. The overexpression of miR-200b-3p could promote endothelial cells apoptosis under oxidative stress by targeting HDAC4 inhibition. Conclusions Our study suggests that EAT derived miR-200b-3p promoted oxidative stress induced endothelial cells damage by targeting HDAC4, which may provide a new and promising therapeutic target for AS.

scholarly journals Tuberculosis latent infection in health care workers: oxidative stress and Quantiferon-TB Plus

2020 ◽  
Vol 30 (Supplement_5) ◽  
Author(s):  
A Santoro ◽  
S Petrillo ◽  
P Nijhawan ◽  
M G Gallo ◽  
R Brugaletta ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Health Care ◽  
Health Care Workers ◽  
Diagnostic Performance ◽  
Expression Profiles ◽  
Antioxidant Response ◽  
Reduced Form ◽  
Antioxidant Genes ◽  
Care Workers ◽  
Latent Tb

Abstract Background This study moves from recent evidences highlighting: 1) the high sensitivity of Mycobacterium tuberculosis (MT) to perturbation of redox homeostasis induced by oxidative stress; 2) the improvement of Tuberculosis (TB) diagnosis following the introduction of Quantiferon-TB Plus (QFT-Plus) assay. Methods The QFT-Plus diagnostic performance and the blood antioxidant capacity, expressed as ratio between oxidized (GSSG) and reduced (GSH) forms of glutathione, were determined on three selected populations (40 Health care workers (HCWs) controls, 63 latent TB HCWs, 8 active TB patients). Quantitative Real Time PCR analysis on leukocytes of active TB patients was also performed, in order to identify “redox profiles” of genes mainly involved in the antioxidant response. Results 1) The glutathione homeostasis was shifted towards an oxidative status in active TB patients respect to controls, as evidenced by the significant decrease of the ratio between free and total GSH, an indirect index of oxidative stress. More reducing conditions were observed in latent TB subjects. 2) The expression profiles of antioxidant genes confirmed the major susceptibility of active TB patients to oxidative stress compared to controls, and highlighted a great individual variability. 3) The diagnostic performance of QFT-Plus test present a moderate concordance with QFT-GIT one, in this preliminary phase. Conclusions Glutathione has anti-mycobacterial effects in its reduced form GSH, thus the quantification of Free/Total GSH ratio may represent a systemic marker of TB infection and be useful in developing combined therapies. Moreover, the identification of personalized redox profiles will additionally provide an individual antioxidant response to the infection. This project was funded by the Ministry of Health (RF 2016) Key messages LTBI management represents an objective of primary importance in the field of occupational medicine in order to define a personalized prevention in HCW. A new approach that combines biochemical determinations of redox biomarkers and gene expression in blood will be a novel biomarkers of tuberculosis.

Skeletal-Muscle Metabolic Reprogramming in ALS-SOD1 G93G Mice Predates Disease Onset and is a Promising Therapeutic Target

2019 ◽  
Author(s):  
Silvia Scaricamazza ◽  
Illari Salvatori ◽  
Giacomo Giacovazzo ◽  
Jean Philippe Loeffler ◽  
Frederique Renè ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Therapeutic Target ◽  
Disease Onset ◽  
Metabolic Reprogramming ◽  
Promising Therapeutic Target
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