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https://www.readbyqxmd.com/read/29149616/protective-effects-of-proanthocyanidins-against-cadmium-induced-testicular-injury-through-the-modification-of-nrf2-keap1-signal-path-in-rats
#1
Liu He, Peng Li, Li-Hui Yu, Lin Li, Yi Zhang, Yang Guo, Miao Long, Jian-Bin He, Shu-Hua Yang
The purpose of this study was to evaluate the potential chemoprotective effects of proanthocyanidins (PAs) against cadmium (Cd)-induced oxidative damage of testes via Nrf2-Keap1 signal pathway in rats. Briefly, by using biochemical histological analysis, as well as the real time PCR and western blot approach, oxidative damage in rat testicular tissue was observed after exposure to Cd. In addition, significant down-regulations of mRNA and protein levels of nuclear erythroid 2-related factor 2 (Nrf2) and heme oxygenase 1 (HO-1), γ-glutamyl cysteine synthetase (γ-GCS), glutathione peroxidase (GSH-Px) and quinone oxidoreductase 1 (NQO1), as well as a significant up-regulation of Kelch sample related protein-1 (Keap1) levels in testicular tissue were observed after Cd exposure...
November 3, 2017: Environmental Toxicology and Pharmacology
https://www.readbyqxmd.com/read/29147905/transcriptional-regulation-of-dj-1
#2
Kazuko Takahashi-Niki, Takeshi Niki, Sanae M M Iguchi-Ariga, Hiroyoshi Ariga
DJ-1 is an oncogene and also a causative gene for familial Parkinson's disease. DJ-1 has various functions, and the oxidative status of a cysteine residue at position 106 (C106) is crucial for determination of the activation level of DJ-1.DJ-1 binds to many proteins, including various transcription factors, and acts as a coactivator or corepressor for regulating their target genes without direct binding to DNA, thereby affecting various cell functions. DJ-1-regulating transcription factors and their modified proteins are the androgen receptor and its regulatory proteins, p53; polypyrimidine tract-binding protein-associated splicing factor (PSF); Keap1, an inhibitor for nuclear factor erythroid2-related factor 2 (Nrf2); sterol regulatory element-binding protein (SREBP); Ras-responsive element-binding protein (RREB1); signal transducer and activator of transcription 1 (STAT1); and Nurr1...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/29140578/alleviation-of-cadmium-induced-oxidative-stress-by-trehalose-via-inhibiting-the-nrf2-keap1-signaling-pathway-in-primary-rat-proximal-tubular-cells
#3
Xin-Yu Wang, Zhen-Yong Wang, Yi-Song Zhu, Si-Ming Zhu, Rui-Feng Fan, Lin Wang
Nuclear factor erythroid 2-related factor 2 (Nrf2) is a transcription factor that regulates a cluster of oxidative stress-inducible genes in cells. Here, we aimed to investigate whether trehalose (Tre) protects primary rat proximal tubular (rPT) cells against cadmium (Cd)-induced oxidative stress via Nrf2 antioxidant pathway. Data showed that Tre treatment inhibited Nrf2 nuclear translocation and restored the decline in Kelch-like ECH-associated protein 1 (Keap1) protein level in Cd-exposed rPT cells. Moreover, Cd-activated Nrf2 target genes, including phase II detoxifying enzymes, that is, NAD(P)H quinone oxidoreductase 1 and heme oxygenase-1, direct antioxidant proteins, that is, glutathione peroxidase, superoxide dismutase, catalase, and glutathione biosynthesis-related proteins, that is, glutamatecysteine ligase catalytic subunit, glutamate cysteine ligase modifier subunit, and glutathione reductase, were all downregulated by co-treatment with Tre...
November 15, 2017: Journal of Biochemical and Molecular Toxicology
https://www.readbyqxmd.com/read/29136497/oncogene-stimulated-congestion-at-the-keap1-stress-signaling-hub-allows-bypass-of-nrf2-and-induction-of-nrf2-target-genes-that-promote-tumor-survival
#4
John D Hayes, Albena T Dinkova-Kostova
In this issue of Cancer Cell, Ge et al. show that overexpression of the oncoprotein iASPP in cancer cells provokes NRF2-mediated induction of cytoprotective genes, because it logjams the ubiquitin ligase substrate adaptor function of KEAP1 by virtue of the fact that it possesses a novel DLT-containing KEAP1-interaction motif.
November 13, 2017: Cancer Cell
https://www.readbyqxmd.com/read/29136249/natural-polyphenol-chlorogenic-acid-protects-against-acetaminophen-induced-hepatotoxicity-by-activating-erk-nrf2-antioxidative-pathway
#5
Mengjuan Wei, Zhiyong Zheng, Liang Shi, Yao Jin, Lili Ji
Hepatotoxicity due to acetaminophen (APAP) overdose is a leading cause of drug-induced acute liver failure in clinic. Chlorogenic acid (CGA), a dietary polyphenol, was reported to prevent APAP-induced liver injury in our previous studies. This study aims to investigate the protection provided by CGA against APAP-induced hepatotoxicity via focusing on nuclear factor erythroid 2-related factor 2 (Nrf2) and extracellular regulated protein kinases (ERK)1/2. CGA prevented APAP-induced oxidative liver injury and enhanced Nrf2 activation in mice and in hepatocytes in vitro...
November 10, 2017: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/29135079/cigarette-smoke-extract-and-isoprene-resulted-in-the-induction-of-apoptosis-and-autophagy-in-human-placenta-choriocarcinoma-jeg-3-cells
#6
Hae-Miru Lee, Kyung-Chul Choi
In this study, the effects of cigarette smoke (CS) on the induction of apoptosis via reactive oxygen species (ROS) production and endoplasmic reticulum stress (ER stress) of JEG-3 human choriocarcinoma cells were examined to confirm the relationship between CS and placenta development. Upon TUNEL assay, CS extract (3R4F; 0.3 and 2.1 μM) increased JEG-3 apoptosis. Western blot assay revealed that the protein expressions of p53, Bax, and CCAAT-enhancer-binding protein homologous protein (CHOP) increased, while the levels of Bcl-2 were reduced following CS extract treatment...
November 14, 2017: Environmental Toxicology
https://www.readbyqxmd.com/read/29128526/functional-analysis-of-cullin-3-e3-ligases-in-tumorigenesis
#7
REVIEW
Ji Cheng, Jianping Guo, Zhiwei Wang, Brian J North, Kaixiong Tao, Xiangpeng Dai, Wenyi Wei
Cullin 3-RING ligases (CRL3) play pivotal roles in the regulation of various physiological and pathological processes, including neoplastic events. The substrate adaptors of CRL3 typically contain a BTB domain that mediates the interaction between Cullin 3 and target substrates to promote their ubiquitination and subsequent degradation. The biological implications of CRL3 adaptor proteins have been well described where they have been found to play a role as either an oncogene, tumor suppressor, or can mediate either of these effects in a context-dependent manner...
November 8, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29126723/design-synthesis-and-evaluation-of-ndga-analogues-as-potential-anti-ischemic-stroke-agents
#8
Lili Huang, Jiabing Wang, Liping Chen, Min Zhu, Shoubiao Wu, Shenghui Chu, Yuantie Zheng, Ziliang Fan, Jiafeng Zhang, Wulan Li, Dahui Chen, Xiufei Yang, Sicen Wang, Peihong Qiu, Jianzhang Wu
Exogenous supplementation of antioxidants with ROS scavenging activity would be a potential therapy to cerebral ischemia-reperfusion injury in stroke. In the present study, a series of NDGA analogues with attenuation oxidative stress by directly scavenging ROS and indirectly through keap1/Nrf2/ARE pathway activation were designed and synthesized. All analogues were found to effectively remove ROS directly by DPPH radical scavenging assay, and compound 3a conferred potent protection from the oxidative injury in PC12 cells via promoting Nrf2 to translocate into nucleus and increasing expression of heme oxygenase-1(HO-1), where strongly reduced intracellular ROS level indirectly...
October 16, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29125494/cognitive-enhancing-and-antioxidant-effects-of-tetrahydroxystilbene-glucoside-in-a%C3%AE-1-42-induced-neurodegeneration-in-mice
#9
Miao Xie, Geng Zhang, Wei Yin, Xin-Xin Hei, Tao Liu
Polyhydroxy stilbenes have been reported to possess various biological activities, and have potential in the treatment of Alzheimer's disease (AD). Tetrahydroxystilbene glucoside is one of the major polyhydroxy stilbenes, which provides underlying therapeutic activities for neuroprotective actions in various experimental conditions. This study intends to investigate the impact of tetrahydroxystilbene glucoside remedy for cognitive disorder and oxidative stress in Aβ1-42-induced AD mice and to clarify the mechanisms of action through Keap1/Nrf2 pathway...
November 7, 2017: Journal of Integrative Neuroscience
https://www.readbyqxmd.com/read/29121589/pharmacological-targeting-of-gsk-3-and-nrf2-provides-neuroprotection-in-a-preclinical-model-of-tauopathy
#10
Antonio Cuadrado, Sebastian Kügler, Isabel Lastres-Becker
Tauopathies are a group of neurodegenerative disorders where TAU protein is presented as aggregates or is abnormally phosphorylated, leading to alterations of axonal transport, neuronal death and neuroinflammation. Currently, there is no treatment to slow progression of these diseases. Here, we have investigated whether dimethyl fumarate (DMF), an inducer of the transcription factor NRF2, could mitigate tauopathy in a mouse model. The signaling pathways modulated by DMF were also studied in mouse embryonic fibroblast (MEFs) from wild type or KEAP1-deficient mice...
November 6, 2017: Redox Biology
https://www.readbyqxmd.com/read/29119264/keap1-nrf2-signaling-pathway-confers-resilience-versus-susceptibility-to-inescapable-electric-stress
#11
Ji-Chun Zhang, Wei Yao, Chao Dong, Mei Han, Yukihiko Shirayama, Kenji Hashimoto
The transcription factor Keap1-Nrf2 signaling plays a key role in the oxidative stress which is involved in psychiatric disorders. In the learned helplessness (LH) paradigm, protein levels of Keap1 and Nrf2 in the prefrontal cortex and dentate gyrus of hippocampus from LH (susceptible) rats were lower than control and non-LH (resilience) rats. Furthermore, protein expressions of Keap1 and Nrf2 in the parietal cortex from major depressive disorder, schizophrenia, and bipolar disorder were lower than controls...
November 8, 2017: European Archives of Psychiatry and Clinical Neuroscience
https://www.readbyqxmd.com/read/29117896/discovery-of-a-head-to-tail-cyclic-peptide-as-the-keap1-nrf2-protein-protein-interaction-inhibitor-with-high-cell-potency
#12
Meng-Chen Lu, Qiong Jiao, Tian Liu, Shi-Jie Tan, Hai-Shan Zhou, Qi-Dong You, Zheng-Yu Jiang
Directly disrupting Keap1-Nrf2 protein-protein interaction (PPI) has emerged as a novel way to activate Nrf2. Peptide Keap1-Nrf2 PPI inhibitors have been reported with high Keap1 binding affinity. However, these peptide inhibitors show weak activity in cells. In this study, the head-to-tail cyclic strategy was applied in the development of peptide inhibitors. The privileged residue sequence with minimal acidic residues was used as the template for the cyclic peptide, and the appropriate conjugation method was designed based on the peptide-Keap1 binding mode...
October 19, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29115468/curcumin-alleviates-liver-oxidative-stress-in-type-1-diabetic-rats
#13
Zhenglu Xie, Binbin Wu, Guozhi Shen, Xiaqing Li, Qianying Wu
The aim of the present study was to determine the effects of curcumin on antioxidants using a rat model of type 1 diabetes. Seven‑week‑old male Sprague‑Dawley rats were injected with Streptozotocin (STZ) intraperitoneally to induce this model, and then treated with 1.0% curcumin (weight ratio) mixed in their diet for 21 days. The present study included three groups: Control group (NC), diabetic rat model group (DC) and a curcumin treated group (Diab‑Cur). The results demonstrated that curcumin treatment markedly decreased the blood glucose levels, plasma malondialdehyde concentration and plasma activity of glutathione peroxidase (GSH‑Px) and catalase (CAT); however, it increased the plasma superoxide dismutase (SOD) and insulin levels...
October 26, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29110908/corrigendum-to-microrna-140-5p-attenuated-oxidative-stress-in-cisplatin-induced-acute-kidney-injury-by-activating-nrf2-are-pathway-through-a-keap1-independent-mechanism-exp-cell-res-2017-292-302
#14
Weitang Liao, Zongjie Fu, Yanfang Zou, Dan Wen, Hongkun Ma, Fangfang Zhou, Yongxi Chen, Mingjun Zhang, Wen Zhang
No abstract text is available yet for this article.
October 27, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/29107745/respiratory-syncytial-virus-induces-nrf2-degradation-through-a-promyelocytic-leukemia-protein-ring-finger-protein-4-dependent-pathway
#15
Narayana Komaravelli, Maria Ansar, Roberto P Garofalo, Antonella Casola
Respiratory syncytial virus (RSV) is the most important cause of viral acute respiratory tract infections and hospitalizations in children, for which no vaccine or specific treatments are available. RSV causes airway mucosa inflammation and cellular oxidative damage by triggering production of reactive oxygen species and by inhibiting at the same time expression of antioxidant enzymes, via degradation of the transcription factor NF-E2-related factor 2 (NRF2). RSV infection induces NRF2 deacetylation, ubiquitination, and degradation through a proteasome-dependent pathway...
October 28, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/29106766/antioxidant-responses-and-deregulation-of-epigenetic-writers-and-erasers-link-oxidative-stress-and-dna-methylation-in-bovine-blastocysts
#16
Monalisa M Bomfim, Gabriella M Andrade, Maite Del Collado, Juliano R Sangalli, Patrícia K Fontes, Marcelo F G Nogueira, Flávio V Meirelles, Juliano C da Silveira, Felipe Perecin
Early mammalian embryos derived from in vitro fertilization are exposed to conditions distinct from the native oviduct-uterine environment, including atmospheric oxygen that promotes cellular oxidative stress and alters gene expression. High oxygen partial pressure during embryo development is associated with low pregnancy rates and increased embryonic apoptosis. We investigated how bovine embryos responded to high (20% O2 ) or low (5% O2 ) oxygen partial pressure during in vitro culture, evaluating levels of reactive oxygen species (ROS) as well as changes in the expression of oxidative stress- and epigenetic-related transcripts and miRNAs in blastocysts...
November 6, 2017: Molecular Reproduction and Development
https://www.readbyqxmd.com/read/29096944/an-in-vitro-inflammation-model-to-study-the-nrf2-and-nf-%C3%AE%C2%BAb-crosstalk-in-presence-of-ferulic-acid-as-modulator
#17
Nadia Lampiasi, Giovanna Montana
The aim of this study was to evaluate the crosstalk between Nrf2 and NF-κB signaling pathways and to explore the modulating activity actuated by ferulic acid. In the inflammation process, a key player is the nuclear factor-κB (NF-κB) transcription factor pathway. On the contrary, the activation of Nrf2 inhibits inflammation and impairs degenerative disease providing an interface between redox and anti-inflammatory responses. Recent studies have demonstrated that protein phosphorylation of IKK complex is a potential mechanism for the activation of both Nrf2 and NF-κB pathways...
October 27, 2017: Immunobiology
https://www.readbyqxmd.com/read/29094331/pterostilbene-protects-against-uraemia-serum-induced-endothelial-cell-damage-via-activation-of-keap1-nrf2-ho-1-signaling
#18
Zhi-Wei Chen, Hai-Feng Miu, Hui-Ping Wang, Zhi-Niu Wu, Wen-Juan Wang, Yu-Jing Ling, Xiao-Hui Xu, Hai-Jian Sun, Xia Jiang
Chronic kidney disease causes uremia-related endothelial cell dysfunction associated with high risk for cardiovascular diseases. The vascular endothelium is permanently exposed to uraemic toxins including indoxyl sulfate, which provokes endothelial damage in subjects with end-stage renal disease. Pterostilbene (PT) is identified to be homologous derivative of resveratrol and exerts antioxidant and anti-inflammatory actions. However, the effects of PT on uraemic serum-induced endothelial cell damage have not been elucidated...
November 1, 2017: International Urology and Nephrology
https://www.readbyqxmd.com/read/29090295/neuroprotective-action-of-tea-polyphenols-on-oxidative-stress-induced-apoptosis-through-the-activation-of-the-trkb-creb-bdnf-pathway-and-keap1-nrf2-signaling-pathway-in-sh-sy5y-cells-and-mice-brain
#19
Guoyuan Qi, Yashi Mi, Yiwen Wang, Runnan Li, Shuxian Huang, Xingyu Li, Xuebo Liu
Many studies have shown that oxidative stress is a major cause of cellular injuries in a variety of human diseases including cognitive impairment. Tea polyphenols (TPs), natural plant flavonoids found in tea plant leaves, possess the bioactivity to affect the pathogenesis of several chronic diseases via antioxidant associated mechanisms. However, the possible antioxidant and neuroprotective properties of TPs in the brain of mice housed in constant darkness and in H2O2-stimulated SH-SY5Y cells are yet to be elucidated...
November 1, 2017: Food & Function
https://www.readbyqxmd.com/read/29089357/effects-of-co-occurring-genomic-alterations-on-outcomes-in-patients-with-kras-mutant-non-small-cell-lung-cancer
#20
Kathryn C Arbour, Emmet J Jordan, Hyunjae Ryan Kim, Jordan Dienstag, Helena Yu, Francisco Sanchez-Vega, Piro Lito, Michael F Berger, David B Solit, Matthew D Hellmann, Mark G Kris, Charles M Rudin, Andy Ni, Maria E Arcila, Marc Ladanyi, Gregory J Riely
BACKGROUND: KRAS mutations occur in approximately 25% of patients with non-small cell lung cancer (NSCLC).  Despite the uniform presence of KRAS mutations, patients with KRAS-mutant NSCLC can have a heterogeneous clinical course. Since the pattern of co-occurring mutations may describe different biological subsets of patients with KRAS-mutant lung adenocarcinoma, we explored the effects of co-occurring mutations on patient outcomes and response to therapy. METHODS: We identified patients with advanced KRAS-mutant NSCLC and evaluated the most common co-occurring genomic alterations...
October 31, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
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