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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...
August 21, 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
Yang Yang, Tiefeng Jin, Shuangping Liu, Liyan Chen, Lijuan Lin, Hongxiu Han, Longshan Li, Zhenhua Lin
OBJECTIVE: To investigate the significance of NADPH quinine oxidoreductase 1 (NQO1) protein overexpression on prognostic evaluation of head and neck squamous cell carcinoma (HNSCC). METHODS: NQO1 protein was detected in 162 of HNSCC, 45 cases of adjacent nontumor tissues and 26 samples of normal head and neck epithelia using EnVision immunohistochemical. Correlation between NQO1 overexpression and patients prognosis was also analyzed. RESULTS: The positive rate and strongly positive rate of NQO1 protein were 84...
July 2014: Zhonghua Bing Li Xue za Zhi Chinese Journal of Pathology
Yi Xie, Qiu Yue Zhao, Hong Yan Li, Xin Zhou, Yang Liu, Hong Zhang
Oxidative stress is one of the major mechanisms implicated in carbon ion irradiation. Curcumin is a natural phenolic compound with impressive antioxidant properties. What's more, curcumin is recently proved to exert its effects partly radioprotection. In vivo, we investigated the protective effects of curcumin against (12)C(6+)radiation-induced cerebral injury. Our results showed that 4Gy heavy ion radiation-induced spatial strategy and memory decline and reduction of brain superoxide dismutase (SOD) activity levels were all consistently improved by curcumin, and the augmentation of cerebral malonaldehyde (MDA) was lowered by curcumin...
November 2014: Pharmacology, Biochemistry, and Behavior
Yong-Hoon Kim, Jung Hwan Hwang, Kyoung-Shim Kim, Jung-Ran Noh, Gil-Tae Gang, Youngwon Seo, Ki-Hoan Nam, Tae Hwan Kwak, Hee Gu Lee, Chul-Ho Lee
BACKGROUND: Endothelial nitric oxide synthase (eNOS) is involved in blood pressure (BP) regulation through the production of nitric oxide. Sirtuin I (SIRT1), an NAD-dependent protein deacetylase, promotes vascular relaxation through deacetylation and activation of eNOS. β-Lapachone (βL) increases the cellular NAD(+)/NADH ratio by activating NAD(P)H: quinone oxidoreductase 1 (NQO1). In this study, we verified whether activation of NQO1 by βL modulates BP through regulation of eNOS acetylation in a hypertensive animal model...
January 2015: American Journal of Hypertension
Clare F Megarity, Hong Keat Looi, David J Timson
Lot6p (EC; Ylr011wp) is the sole quinone oxidoreductase in the budding yeast, Saccharomyces cerevisiae. Using hexahistidine tagged, recombinant Lot6p, we determined the steady-state enzyme kinetic parameters with both NADH and NADPH as electron donors; no cooperativity was observed with these substrates. The NQO1 inhibitor curcumin, the NQO2 inhibitor resveratrol, the bacterial nitroreductase inhibitor nicotinamide and the phosphate mimic vanadate all stabilise the enzyme towards thermal denaturation as judged by differential scanning fluorimetry...
August 2014: FEMS Yeast Research
S J Allison, J R P Knight, C Granchi, R Rani, F Minutolo, J Milner, R M Phillips
Most cancer cells use aerobic glycolysis to fuel their growth. The enzyme lactate dehydrogenase-A (LDH-A) is key to cancer's glycolytic phenotype, catalysing the regeneration of nicotinamide adenine dinucleotide (NAD(+)) from reduced nicotinamide adenine dinucleotide (NADH) necessary to sustain glycolysis. As such, LDH-A is a promising target for anticancer therapy. Here we ask if the tumour suppressor p53, a major regulator of cellular metabolism, influences the response of cancer cells to LDH-A suppression...
2014: Oncogenesis
Seung Taek Nam, Jung Hwan Hwang, Dae Hong Kim, Mi Jung Park, Ik Hwan Lee, Hyo Jung Nam, Jin Ku Kang, Sung Kuk Kim, Jae Sam Hwang, Hyo Kyun Chung, Minho Shong, Chul-Ho Lee, Ho Kim
NADH:quinone oxidoreductase 1 (NQO1) is known to be involved in the regulation of energy synthesis and metabolism, and the functional studies of NQO1 have largely focused on metabolic disorders. Here, we show for the first time that compared to NQO1-WT mice, NQO1-KO mice exhibited a marked increase of permeability and spontaneous inflammation in the gut. In the DSS-induced colitis model, NQO1-KO mice showed more severe inflammatory responses than NQO1-WT mice. Interestingly, the transcript levels of claudin and occludin, the major tight junction molecules of gut epithelial cells, were significantly decreased in NQO1-KO mice...
September 2014: BMB Reports
Yong-Hoon Kim, Jung Hwan Hwang, Kyung-Shim Kim, Jung-Ran Noh, Gil-Tae Gang, Won Keun Oh, Kyeong-Hoon Jeong, Tae Hwan Kwak, Hueng-Sik Choi, In-Kyu Lee, Chul-Ho Lee
AIMS: Guanosine 5'-triphosphate cyclohydrolase-1 (GTPCH-1) is a rate-limiting enzyme in de-novo synthesis of tetrahydrobiopterin (BH4), an essential cofactor for endothelial nitric oxide synthase (eNOS) coupling. Adenosine 5'-monophosphate-activated protein kinase (AMPK) is crucial for GTPCH-1 preservation, and tumor suppressor kinase liver kinase B1 (LKB1), an upstream kinase of AMPK, is activated by NAD-dependent class III histone deacetylase sirtuin 1 (SIRT1)-mediated deacetylation...
February 2014: Journal of Hypertension
Gi-Su Oh, Hyung-Jin Kim, Jae-Hyuck Choi, Aihua Shen, Seong-Kyu Choe, Anzani Karna, Seung Hoon Lee, Hyang-Jeong Jo, Sei-Hoon Yang, Tae Hwan Kwak, Chul-Ho Lee, Raekil Park, Hong-Seob So
UNLABELLED: Cisplatin is a widely used chemotherapeutic agent for the treatment of various tumors. In addition to its antitumor activity, cisplatin affects normal cells and may induce adverse effects, such as ototoxicity, nephrotoxicity, and neuropathy. Various mechanisms, such as DNA adduct formation, mitochondrial dysfunction, oxidative stress, and inflammatory responses, are critically involved in cisplatin-induced adverse effects. As NAD(+) is a cofactor for various enzymes associated with cellular homeostasis, we studied the effects of increased NAD(+) levels by means of NAD(P)H: quinone oxidoreductase 1 (NQO1) activation using a known pharmacological activator (β-lapachone) in wild-type and NQO1(-/-) mice on cisplatin-induced renal dysfunction in vivo...
March 2014: Kidney International
Jiyeong Kim, Su-Kyung Kim, Hwa-Kyung Kim, Mark P Mattson, Dong-Hoon Hyun
BACKGROUND: Recent findings suggest that NADH-dependent enzymes of the plasma membrane redox system (PMRS) play roles in the maintenance of cell bioenergetics and oxidative state. Neurons and tumor cells exhibit differential vulnerability to oxidative and metabolic stress, with important implications for the development of therapeutic interventions that promote either cell survival (neurons) or death (cancer cells). METHODS AND FINDINGS: Here we used human neuroblastoma cells with low or high levels of the PMRS enzyme NADH-quinone oxidoreductase 1 (NQO1) to investigate how the PMRS modulates mitochondrial functions and cell survival...
2013: PloS One
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