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Meng-Ge Zhao, Xue-Ping Sheng, Ya-Ping Huang, Yi-Ting Wang, Cui-Hua Jiang, Jian Zhang, Zhi-Qi Yin
The effects of triterpenic acids-enriched fraction from Cyclocarya paliurus (CPT) on nonalcoholic fatty liver disease (NAFLD) were investigated using in vivo and in vitro models. In high fat diet-induced Wister rats, CPT significantly increased superoxide dismutase (SOD) activity and glutathione/oxidized glutathione (GSH/GSSG) ratio, reduced malondialdehyde (MDA) and protein carbonyl (PCO) levels. Moreover, CPT restored mitochondrial membrane potential dysfunction, decreased cytochrome P450 enzyme 2E1 (CYP2E1) activity, improved nuclear factor erythroid 2-related factor 2 (Nrf2) and Nrf2-mediated antioxidant enzyme heme oxygenase1 (HO-1) expression...
May 15, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Dora Ravasz, Gergely Kacso, Viktoria Fodor, Kata Horvath, Vera Adam-Vizi, Christos Chinopoulos
Provision of NAD+ for oxidative decarboxylation of alpha-ketoglutarate to succinyl-CoA by the ketoglutarate dehydrogenase complex (KGDHC) is critical for maintained operation of succinyl-CoA ligase yielding high-energy phosphates, a process known as mitochondrial substrate-level phosphorylation (mSLP). We have shown previously that when NADH oxidation by complex I is inhibited by rotenone or anoxia, mitochondrial diaphorases yield NAD+ , provided that suitable quinones are present (Kiss G et al., FASEB J 2014, 28:1682)...
May 7, 2018: Biochimica et Biophysica Acta
Alberto Diaz-Ruiz, Michael Lanasa, Joseph Garcia, Hector Mora, Frances Fan, Alejandro Martin-Montalvo, Andrea Di Francesco, Miguel Calvo-Rubio, Andrea Salvador-Pascual, Miguel A Aon, Kenneth W Fishbein, Kevin J Pearson, Jose Manuel Villalba, Placido Navas, Michel Bernier, Rafael de Cabo
Calorie restriction (CR) is one of the most robust means to improve health and survival in model organisms. CR imposes a metabolic program that leads to increased stress resistance and delayed onset of chronic diseases, including cancer. In rodents, CR induces the upregulation of two NADH-dehydrogenases, namely NAD(P)H:quinone oxidoreductase 1 (Nqo1) and cytochrome b5 reductase 3 (Cyb5r3), which provide electrons for energy metabolism. It has been proposed that this upregulation may be responsible for some of the beneficial effects of CR, and defects in their activity are linked to aging and several age-associated diseases...
April 28, 2018: Aging Cell
Yan Wang, Wei Qi, Li Zhang, Zhenguang Ying, Ou Sha, Chunman Li, Lanhai Lü, Xiangyan Chen, Zhenzhong Li, Feng Niu, Fang Xue, Dong Wang, Tzi-Bun Ng, Lihong Zhang
Background: DL-3-n-butylphthalide (NBP) is a drug for treating acute ischemic stroke, and may play a neuroprotective role by acting on multiple active targets. The aim of this study was to predict the target proteins of NBP in mammalian cells. Methods: The similarity ensemble approach search tool (SEArch), one of the commonly used public bioinformatics tools for target prediction, was employed in the experiment. The molecular docking of NBP to target proteins was performed by using the three-dimensional (3-D) crystal structure, substrate free...
October 2017: Quantitative Imaging in Medicine and Surgery
Jinzi Wu, Xiaoting Luo, Nopporn Thangthaeng, Nathalie Sumien, Zhenglan Chen, Margaret A Rutledge, Siqun Jing, Michael J Forster, Liang-Jun Yan
It is well established that NADH/NAD+ redox balance is heavily perturbed in diabetes, and the NADH/NAD+ redox imbalance is a major source of oxidative stress in diabetic tissues. In mitochondria, complex I is the only site for NADH oxidation and NAD+ regeneration and is also a major site for production of mitochondrial reactive oxygen species (ROS). Yet how complex I responds to the NADH/NAD+ redox imbalance and any potential consequences of such response in diabetic pancreas have not been investigated. We report here that pancreatic mitochondrial complex I showed aberrant hyperactivity in either type 1 or type 2 diabetes...
September 2017: Biochemistry and Biophysics Reports
Xian Wu, Mingyue Song, Zili Gao, Yue Sun, Minqi Wang, Fang Li, Jinkai Zheng, Hang Xiao
Nobiletin (NOB) is a major citrus polymethoxyflavone (PMF) with various beneficial biological activities. We reported previously that dietary NOB significantly inhibited colitis-associated colon carcinogenesis in azoxymethane (AOM)/dextran sulfate sodium (DSS)-treated mice, and the chemopreventive effects were associated with NOB metabolites found in the mouse colonic tissues. In this study, to better understand the role of colonic metabolites of NOB, we determined the anti-inflammation and anticancer effects of a mixture of NOB and its major metabolites (NOB-Met) at the concentrations equivalent to those found in colonic tissues of NOB-fed mice...
April 2017: Journal of Nutritional Biochemistry
Dong Ryun Gu, Joon No Lee, Gi-Su Oh, Hyung Jin Kim, Min Seuk Kim, Seoung Hoon Lee
β-lapachone (β-L) is a substrate of reduced nicotinamide adenine dinucleotide (NADH): quinone oxidoreductase 1 (NQO1). NQO1 reduces quinones to hydroquinones using NADH as an electron donor and consequently increases the intracellular NAD+/NADH ratio. The activation of NQO1 by β-L has beneficial effects on several metabolic syndromes, such as obesity, hypertension, and renal injury. However, the effect of β-L on bone metabolism remains unclear. Here, we show that β-L might be a potent inhibitor of receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclastogenesis...
January 22, 2017: Biochemical and Biophysical Research Communications
Jinzi Wu, Zhen Jin, Liang-Jun Yan
Although the lung is one of the least studied organs in diabetes, increasing evidence indicates that it is an inevitable target of diabetic complications. Nevertheless, the underlying biochemical mechanisms of lung injury in diabetes remain largely unexplored. Given that redox imbalance, oxidative stress, and mitochondrial dysfunction have been implicated in diabetic tissue injury, we set out to investigate mechanisms of lung injury in diabetes. The objective of this study was to evaluate NADH/NAD+ redox status, oxidative stress, and mitochondrial abnormalities in the diabetic lung...
April 2017: Redox Biology
Gi-Su Oh, Su-Bin Lee, Anjani Karna, Hyung-Jin Kim, AiHua Shen, Arpana Pandit, SeungHoon Lee, Sei-Hoon Yang, Hong-Seob So
BACKGROUND: Idiopathic pulmonary fibrosis is a common interstitial lung disease; it is a chronic, progressive, and fatal lung disease of unknown etiology. Over the last two decades, knowledge about the underlying mechanisms of pulmonary fibrosis has improved markedly and facilitated the identification of potential targets for novel therapies. However, despite the large number of antifibrotic drugs being described in experimental pre-clinical studies, the translation of these findings into clinical practices has not been accomplished yet...
October 2016: Tuberculosis and Respiratory Diseases
Hwa-Kyung Kim, Tae Gen Son, Dong-Gyu Jo, Dong Chung Kim, Dong-Hoon Hyun
Lipid-soluble ginseng extracts (LSGE) is known to inhibit many types of cancer cells through arresting cell cycle and inducing apoptosis. Usually, normal cells are can also be damaged by anti-tumor reagents. The plasma membrane redox system (PMRS) is enhanced to compensate mitochondrial dysfunction and impaired energy metabolism. NADH-quinone oxidoreductase 1 (NQO1), a plasma membrane redox enzyme, is known to be induced by panaxytriol, one of components of lipid-soluble ginseng extracts (LSGE). The objective of this study was determine the mechanisms of NQO1 involved in neuroprotection in response to cytotoxicity induced by LSGE...
October 2016: Archives of Pharmacal Research
Joshua P Gray, Shpetim Karandrea, Delaine Zayasbazan Burgos, Anil A Jaiswal, Emma A Heart
NQO1 (NAD(P)H-quinone oxidoreductase 1) reduces quinones and xenobiotics to less-reactive compounds via 2-electron reduction, one feature responsible for the role of NQO1 in antioxidant defense in several tissues. In contrast, NADPH cytochrome P450 oxidoreductase (CYP450OR), catalyzes the 1-electron reduction of quinones and xenobiotics, resulting in enhanced superoxide formation. However, to date, the roles of NQO1 and CYP450OR in pancreatic β-cell metabolism under basal conditions and oxidant challenge have not been characterized...
November 16, 2016: Toxicology Letters
Weon Sup Shin, Jiyou Han, Peter Verwilst, Rajesh Kumar, Jong-Hoon Kim, Jong Seung Kim
UNLABELLED: The development of targeted and effective theranostic (therapeutic and diagnostic) chemotherapeutic agents is highly desirable for precise diagnosis and treatment of cancer. To realize this goal, we developed a cancer-targeting and enzyme-triggered theranostic prodrug 1, containing 7-ethyl-10-hydroxycamptothecin (SN-38), a well-known anticancer drug, which inhibits topoisomerase I in the cell nucleus; hydroquinone as an enzyme-triggered moiety; and biotin as a cancer targeting unit...
May 18, 2016: Bioconjugate Chemistry
Seung Taek Nam, Jung Hwan Hwang, Dae Hong Kim, Li Fang Lu, Ji Hong, Peng Zhang, I Na Yoon, Jae Sam Hwang, Hyo Kyun Chung, Minho Shong, Chul-Ho Lee, Ho Kim
Clostridium difficile toxin A causes acute gut inflammation in animals and humans. It is known to downregulate the tight junctions between colonic epithelial cells, allowing luminal contents to access body tissues and trigger acute immune responses. However, it is not yet known whether this loss of the barrier function is a critical factor in the progression of toxin A-induced pseudomembranous colitis. We previously showed that NADH:quinone oxidoreductase 1 (NQO1) KO (knockout) mice spontaneously display weak gut inflammation and a marked loss of colonic epithelial tight junctions...
August 28, 2016: Journal of Microbiology and Biotechnology
Yi Hui Yang, Yu Zhang, Wei Chen, Ying Wang, Song Cao, Tian Yu, Haiying Wang
Ischemic postconditioning (IPO) had been reported as a promising method against myocardial ischemia-reperfusion (I/R) injury, but IPO was later proved with poor clinical benefit. In this study, we compared the protective effects of pinacidil-postconditioning (PPO) and IPO against myocardial I/R injury. Langendorff rat hearts were randomly assigned to one of the following groups (n=8 each): Control group, I/R group (40min ischemia and 60min reperfusion), IPO group (6 successive cycles of 10s reperfusion per 10s occlusion before fully reperfusion), PPO group (perfused with 50μM pinacidil for 5min before reperfusion)...
June 5, 2016: European Journal of Pharmacology
Arpana Pandit, Hyung-Jin Kim, Gi-Su Oh, AiHua Shen, Su-Bin Lee, Dipendra Khadka, SeungHoon Lee, Hyeok Shim, Sei-Hoon Yang, Eun-Young Cho, Kang-Beom Kwon, Tae Hwan Kwak, Seong-Kyu Choe, Raekil Park, Hong-Seob So
Although cisplatin is a widely used anticancer drug for the treatment of a variety of tumors, its use is critically limited because of adverse effects such as ototoxicity, nephrotoxicity, neuropathy, and gastrointestinal damage. Cisplatin treatment increases oxidative stress biomarkers in the small intestine, which may induce apoptosis of epithelial cells and thereby elicit damage to the small intestine. Nicotinamide adenine dinucleotide (NAD(+)) is a cofactor for various enzymes associated with cellular homeostasis...
November 27, 2015: Biochemical and Biophysical Research Communications
Prasada Rao S Kodavanti, Joyce E Royland, Debra A Moore-Smith, Jonathan Besas, Judy E Richards, Tracey E Beasley, Paul Evansky, Philip J Bushnell
The effects of exposure to volatile organic compounds (VOCs), which are of concern to the EPA, are poorly understood, in part because of insufficient characterization of how human exposure duration impacts VOC effects. Two inhalation studies with multiple endpoints, one acute and one subchronic, were conducted to seek effects of the VOC, toluene, in rats and to compare the effects between acute and subchronic exposures. Adult male Long-Evans rats were exposed to toluene vapor (n=6 per group) at a concentration of 0 or 1019 ± 14 ppm for 6h in the acute study and at 0 ± 0, 10 ± 1...
December 2015: Neurotoxicology
Yuzheng Zhao, Qingxun Hu, Feixiong Cheng, Ni Su, Aoxue Wang, Yejun Zou, Hanyang Hu, Xianjun Chen, Hai-Meng Zhou, Xinzhi Huang, Kai Yang, Qian Zhu, Xue Wang, Jing Yi, Linyong Zhu, Xuhong Qian, Lixin Chen, Yun Tang, Joseph Loscalzo, Yi Yang
The altered metabolism of tumor cells confers a selective advantage for survival and proliferation, and studies have shown that targeting such metabolic shifts may be a useful therapeutic strategy. We developed an intensely fluorescent, rapidly responsive, pH-resistant, genetically encoded sensor of wide dynamic range, denoted SoNar, for tracking cytosolic NAD(+) and NADH redox states in living cells and in vivo. SoNar responds to subtle perturbations of various pathways of energy metabolism in real time, and allowed high-throughput screening for new agents targeting tumor metabolism...
May 5, 2015: Cell Metabolism
Angélica Martínez-Hernández, Emilio J Córdova, Oscar Rosillo-Salazar, Humberto García-Ortíz, Cecilia Contreras-Cubas, Sergio Islas-Andrade, Cristina Revilla-Monsalve, Consuelo Salas-Labadía, Lorena Orozco
Metabolic syndrome (MetS) is among the most important public health problems worldwide, and is recognized as a major risk factor for various illnesses, including type 2 diabetes mellitus, obesity, and cardiovascular diseases. Recently, oxidative stress has been suggested as part of MetS aetiology. The heme oxygenase 1 (HMOX1) and NADH:quinone oxidoreductase 1 (NQO1) genes are crucial mediators of cellular defence against oxidative stress. In the present study, we analysed the associations of HMOX1 (GT)n and NQO1 C609T polymorphisms with MetS and its components...
2015: PloS One
Chuanyang Su, Pu Zhang, Xiufang Song, Qiong Shi, Juanli Fu, Xiaomin Xia, Huiyuan Bai, Lihua Hu, Demei Xu, Erqun Song, Yang Song
Tetrachlorobenzoquinone (TCBQ), a metabolite of industrial herbicide pentachlorophenol, showed hepatotoxicity and genotoxicity through reactive oxygen species (ROS) mechanism in vivo and in vitro models. Nuclear factor erythroid-derived 2-like 2 (Nrf2) is a cellular sensor of oxidative or electrophilic stress, which controls the expression of detoxifying enzymes and antioxidant proteins. Using the human hepatoma HepG2 cell line as an in vitro model, we demonstrated a significant induction of Nrf2 but not its negative regulator Kelch-like ECH-associated protein 1 (Keap1), following exposure to TCBQ...
April 20, 2015: Chemical Research in Toxicology
Mauricio Menacho-Márquez, Carlos J Rodríguez-Hernández, M Ángeles Villaronga, Jorge Pérez-Valle, José Gadea, Borja Belandia, José R Murguía
β-Lapachone (β-lap) is a novel anticancer agent that selectively induces cell death in human cancer cells, by activation of the NQO1 NAD(P)H dehydrogenase and radical oxygen species (ROS) generation. We characterized the gene expression profile of budding yeast cells treated with β-lap using cDNA microarrays. Genes involved in tolerance to oxidative stress were differentially expressed in β-lap treated cells. β-lap treatment generated reactive oxygen species (ROS), which were efficiently blocked by dicoumarol, an inhibitor of NADH dehydrogenases...
2015: Cell Cycle
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