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https://www.readbyqxmd.com/read/28650465/mcu-dependent-mitochondrial-ca-2-inhibits-nad-sirt3-sod2-pathway-to-promote-ros-production-and-metastasis-of-hcc-cells
#1
T Ren, H Zhang, J Wang, J Zhu, M Jin, Y Wu, X Guo, L Ji, Q Huang, H Zhang, H Yang, J Xing
Mitochondrial Ca(2+) signaling, which is strongly dependent on the mitochondrial Ca(2+) uniporter (MCU) complex, has a series of key roles in physiopathological processes, including energy metabolism, reactive oxygen species (ROS) production and cell apoptosis. However, a mechanistic understanding of how the mitochondrial Ca(2+) signaling is remodeled and its functional roles remains greatly limited in cancers, especially in hepatocellular carcinoma. Here we demonstrated that the MCU complex was dysregulated in hepatocellular carcinoma (HCC) cells and significantly correlated with metastasis and poor prognosis of HCC patients...
June 26, 2017: Oncogene
https://www.readbyqxmd.com/read/28646144/using-fractional-intensities-of-time-resolved-fluorescence-to-sensitively-quantify-nadh-nad-with-genetically-encoded-fluorescent-biosensors
#2
Mengfang Chang, Lei Li, Hanyang Hu, Qingxun Hu, Aoxue Wang, Xiaodan Cao, Xiantong Yu, Sanjun Zhang, Yuzheng Zhao, Jinquan Chen, Yi Yang, Jianhua Xu
In this paper, we propose a novel and sensitive ratiometric analysis method that uses the fractional intensities of time-resolved fluorescence of genetically encoded fluorescent NADH/NAD(+) biosensors, Peredox, SoNar, and Frex. When the conformations of the biosensors change upon NADH/NAD(+) binding, the fractional intensities (α i τ i ) have opposite changing trends. Their ratios could be exploited to quantify NADH/NAD(+) levels with a larger dynamic range and higher resolution versus commonly used fluorescence intensity and lifetime methods...
June 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28645327/impact-of-growth-matrix-on-pharmacodynamics-of-antimicrobial-drugs-for-pig-pneumonia-pathogens
#3
Lucy Dorey, Peter Lees
BACKGROUND: The most widely used measure of potency of antimicrobial drugs is Minimum Inhibitory Concentration (MIC). MIC is usually determined under standardised conditions in broths formulated to optimise bacterial growth on a species-by-species basis. This ensures comparability of data between laboratories. However, differences in values of MIC may arise between broths of differing chemical composition and for some drug classes major differences occur between broths and biological fluids such as serum and inflammatory exudate...
June 23, 2017: BMC Veterinary Research
https://www.readbyqxmd.com/read/28637353/hallmarks-of-pulmonary-hypertension-mesenchymal-and-inflammatory-cell-metabolic-reprogramming
#4
Angelo D'Alessandro, Karim El Kasmi, Lydie Plecita-Hlavata, Petr Jezek, Min Li, Hui Zhang, Sachin A Gupte, Kurt Randall Stenmark
The molecular events that promote the development of pulmonary hypertension (PH) are complex and incompletely understood. The complex interplay between the pulmonary vasculature and its immediate microenvironment involving cells of immune system (i.e. macrophages) promotes a persistent inflammatory state, pathological angiogenesis and fibrosis that is driven by metabolic reprogramming of mesenchymal and immune cells. Consistent with previous findings in the field of cancer metabolism, increased glycolytic rates, incomplete glucose and glutamine oxidation to support anabolism and anaplerosis, altered lipid synthesis/oxidation ratios, increased one-carbon metabolism and activation of the pentose phosphate pathway to support nucleoside synthesis are but some of the key metabolic signatures of vascular cells in PH...
June 22, 2017: Antioxidants & Redox Signaling
https://www.readbyqxmd.com/read/28635300/pyridine-dinucleotides-from-molecules-to-man
#5
Joshua P Fessel, William M Oldham
SIGNIFICANCE: Pyridine dinucleotides, NAD and NADP, were discovered over 100 years ago as necessary cofactors for fermentation in yeast extracts. Since that time, these molecules have been recognized as fundamental players in a variety of cellular processes, including energy metabolism, redox homeostasis, cellular signaling, and gene transcription, among many others. Given their critical role as mediators of cellular responses to metabolic perturbations, it is unsurprising that dysregulation of NAD and NADP metabolism has been associated with the pathobiology of many chronic human diseases...
June 21, 2017: Antioxidants & Redox Signaling
https://www.readbyqxmd.com/read/28631845/mild-metabolic-perturbations-alter-succinylation-of-mitochondrial-proteins
#6
Huanlian Chen, Hui Xu, Samuel Potash, Anatoly Starkov, Vsevolod V Belousov, Dmitry S Bilan, Travis T Denton, Gary E Gibson
Succinylation of proteins is widespread, modifies both the charge and size of the molecules, and can alter their function. For example, liver mitochondrial proteins have 1,190 unique succinylation sites representing multiple metabolic pathways. Succinylation is sensitive to both increases and decreases of the NAD(+) -dependent desuccinylase, SIRT5. Although the succinyl group for succinylation is derived from metabolism, the effects of systematic variation of metabolism on mitochondrial succinylation are not known...
June 20, 2017: Journal of Neuroscience Research
https://www.readbyqxmd.com/read/28628905/a-ros-mediated-mitochondrial-pathway-and-nrf2-pathway-activation-are-involved-in-bde-47-induced-apoptosis-in-neuro-2a-cells
#7
Hongmei Chen, Xuexi Tang, Bin Zhou, Zhongyuan Zhou, Ningning Xu, You Wang
Our previous study showed that 2,2'-,4,4'-tetrabromodiphenyl ether (BDE-47) is cytotoxic and induces apoptosis in Neuro-2a cells. In the present study, we aimed to investigate whether nuclear factor (erythroid-derived 2)-like 2 (Nrf2), an antioxidant transcriptional regulator of oxidative stress and apoptosis, is involved in this process. The results of toxicological experiments showed that BDE-47 decreased the cellular mitochondrial membrane potential (MMP) and increased cytochrome c release to the cytoplasm, followed by an increase in intracellular caspase-9 and caspase-3 activity, suggesting that a mitochondrial pathway was involved in the apoptotic process...
June 3, 2017: Chemosphere
https://www.readbyqxmd.com/read/28608874/a-novel-two-photon-fluorescent-probe-with-a-long-stokes-shift-and-a-high-signal-to-background-ratio-for-human-nad-p-h-quinone-oxidoreductase-1-hnqo1-detection-and-imaging-in-living-cells-and-tissues
#8
Dan Pan, Fengyan Luo, Xianjun Liu, Wei Liu, Wen Chen, Feng Liu, Yong-Qing Kuang, Jian-Hui Jiang
In recent years, many activatable fluorescent probes have been developed for hNQO1 detection. However, most of the reported fluorescent probes are susceptible to the interferences of endogenous fluorescence and have the drawback of inadequate penetration depth. Very recently, researchers have reported a two-photon excitation (TPE) fluorescent probe for hNQO1 detection. Nevertheless, this probe only exhibits a compromised signal-to-background ratio, and has not been applied to image hNQO1 in living tissues. Herein, a novel TPE fluorescent probe, trimethyl locked quinone caged Acedan (Q3CA-P), has been developed for hNQO1 detection and imaging in living cells and tissues...
June 13, 2017: Analyst
https://www.readbyqxmd.com/read/28599455/downregulation-of-nad-p-h-quinone-oxidoreductase-1-inhibits-proliferation-cell-cycle-and-migration-of-cholangiocarcinoma-cells
#9
Siriwoot Butsri, Veerapol Kukongviriyapan, Laddawan Senggunprai, Sarinya Kongpetch, Ponsilp Zeekpudsa, Auemduan Prawan
We previously reported that upregulation of NAD(P)H:quinone oxidoreductase 1 (NQO1) in cholangiocarcinoma (CCA; a fatal bile duct cancer) was associated with poor prognosis. It was also demonstrated that the suppression of NQO1 was able to enhance the chemosensitivity of CCA cells. In the present study, in order to elucidate the biological role of NQO1 in CCA, the effects of small interfering RNA (siRNA)-mediated knockdown of NQO1 on cell proliferation, cell cycle and migration were determined in KKU-100 CCA cells, which notably expressed NQO1...
June 2017: Oncology Letters
https://www.readbyqxmd.com/read/28582766/enrichment-and-geochemical-mobility-of-heavy-metals-in-bottom-sediment-of-the-hoedong-reservoir-korea-and-their-source-apportionment
#10
Pyeong-Koo Lee, Min-Ju Kang, Soonyoung Yu, Kyung-Seok Ko, Kyoochul Ha, Seong-Cheon Shin, Jung Han Park
Physicochemical characteristics of bottom sediment in the Hoedong reservoir were studied to evaluate the effectiveness of the reservoir as traps for trace metals. Roadside soil, stream sediment and background soil were also studied for comparison. Sequential extractions were carried out, and lead isotopic compositions of each extraction were determined to apportion Pb sources. Besides, particle size distribution of roadside soil, and metal concentrations and Pb isotopes of each size group were determined to characterize metal contamination...
May 22, 2017: Chemosphere
https://www.readbyqxmd.com/read/28578808/real-time-monitoring-of-intracellular-redox-changes-in-methylococcus-capsulatus-bath-for-efficient-bioconversion-of-methane-to-methanol
#11
Masahito Ishikawa, Yuya Tanaka, Risa Suzuki, Kota Kimura, Kenya Tanaka, Kazuhide Kamiya, Hidehiro Ito, Souichiro Kato, Toshiaki Kamachi, Katsutoshi Hori, Shuji Nakanishi
This study aimed to develop a novel method for real-time monitoring of the intracellular redox states in a methanotroph Methylococcus capsulatus, using Peredox as a genetically encoded fluorescent sensor of the NADH:NAD(+) ratio. As expected, the fluorescence derived from the Peredox-expressing M. capsulatus transformant increased by supplementation of electron donor compounds (methane and formate), while it decreased by specifically inhibiting the methanol oxidation reaction. Electrochemical measurements confirmed that the Peredox fluorescence reliably represents the intracellular redox changes...
May 19, 2017: Bioresource Technology
https://www.readbyqxmd.com/read/28569777/the-novel-hypoxia-inducible-factor-1%C3%AE-inhibitor-idf-11774-regulates-cancer-metabolism-thereby-suppressing-tumor-growth
#12
Hyun Seung Ban, Bo-Kyung Kim, Hongsub Lee, Hwan Mook Kim, Dipesh Harmalkar, Miso Nam, Song-Kyu Park, Kiho Lee, Joon-Tae Park, Inhyub Kim, Kyeong Lee, Geum-Sook Hwang, Misun Won
HIF-1 is associated with poor prognoses and therapeutic resistance in cancer patients. We previously developed a novel hypoxia-inducible factor (HIF)-1 inhibitor, IDF-11774, a clinical candidate for cancer therapy. We also reported that IDF-1174 inhibited HSP70 chaperone activity and suppressed accumulation of HIF-1α. In this study, IDF-11774 inhibited the accumulation of HIF-1α in vitro and in vivo in colorectal carcinoma HCT116 cells under hypoxic conditions. Moreover, IDF-11774 treatment suppressed angiogenesis of cancer cells by reducing the expression of HIF-1 target genes, reduced glucose uptake, thereby sensitizing cells to growth under low glucose conditions, and decreased the extracellular acidification rate (ECAR) and oxygen consumption rate of cancer cells...
June 1, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28554565/antioxidant-mechanism-of-mitochondria-targeted-plastoquinone-skq1-is-suppressed-in-aglycemic-hepg2-cells-dependent-on-oxidative-phosphorylation
#13
Jan Ježek, Hana Engstová, Petr Ježek
Previously suggested antioxidant mechanisms for mitochondria-targeted plastoquinone SkQ1 included: i) ion-pairing of cationic SkQ1(+) with free fatty acid anions resulting in uncoupling; ii) SkQ1H2 ability to interact with lipoperoxyl radical; iii) interference with electron flow at the inner ubiquinone (Q) binding site of Complex III (Qi), involving the reduction of SkQ1 to SkQ1H2 by ubiquinol. We elucidated SkQ1 antioxidant properties by confocal fluorescence semi-quantification of mitochondrial superoxide (Jm) and cytosolic H2O2 (Jc) release rates in HepG2 cells...
May 26, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28537923/aldehyde-dehydrogenase-1a1-increases-nadh-levels-and-promotes-tumor-growth-via-glutathione-dihydrolipoic-acid-dependent-nad-reduction
#14
Baiyun Wang, Xue Chen, Zixi Wang, Wei Xiong, Tao Xu, Xinyuan Zhao, Yang Cao, Yanru Guo, Lin Li, She Chen, Song Huang, Xiaodong Wang, Min Fang, Zhirong Shen
Aldehyde dehydrogenase 1A1 (ALDH1A1) is a member of the aldehyde dehydrogenase superfamily that oxidizes aldehydes to their corresponding acids, reactions that are coupled to the reduction of NAD+ to NADH. We report here that ALDH1A1 can also use glutathione (GSH) and dihydrolipoic acid (DHLA) as electron donors to reduce NAD+ to NADH. The GSH/DHLA-dependent NAD+-reduction activity of ALDH1A1 is not affected by the aldehyde dehydrogenase inhibitor or by mutation of the residues in its aldehyde-binding pocket...
May 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28529598/biological-interaction-of-cigarette-smoking-on-the-association-between-genetic-polymorphisms-involved-in-inflammation-and-the-risk-of-lung-cancer-a-case-control-study-in-japan
#15
Yuzo Yamamoto, Chikako Kiyohara, Saiko Suetsugu-Ogata, Naoki Hamada, Yoichi Nakanishi
Chronic inflammation serves an important role in lung carcinogenesis, thus genetic polymorphisms involved in this pathway may affect the risk of lung cancer. The present case-control study focused on the association between lung cancer risk and genetic polymorphisms involved in inflammatory pathways. The study comprised 462 lung cancer cases and 379 controls from Japan. The roles of interleukin 8 (IL8) rs4073, nuclear factor kappa B (NFκB) rs28362491, cytochrome b-245, alpha polypeptide (CYBA) rs4673, NAD(P) H dehydrogenase, quinone 1 (NQO1) rs1800566, nitric oxide synthase 2 and inducible (NOS2) rs2297518 polymorphisms in lung carcinogenesis were investigated...
May 2017: Oncology Letters
https://www.readbyqxmd.com/read/28528294/isoliquiritigenin-reduces-oxidative-damage-and-alleviates-mitochondrial-impairment-by-sirt1-activation-in-experimental-diabetic-neuropathy
#16
Veera Ganesh Yerra, Anil Kumar Kalvala, Ashutosh Kumar
Sirtuin (SIRT1) inactivation underlies the pathogenesis of insulin resistance and hyperglycaemia-associated vascular complications, but its role in diabetic neuropathy (DN) has not been yet explored. We have evaluated hyperglycaemia-induced alteration of SIRT1 signalling and the effect of isoliquiritigenin (ILQ) on SIRT1-directed AMP kinase (AMPK) and peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) signalling in peripheral nerves of streptozotocin (STZ) (55 mg/kg, ip)-induced diabetic rats and in high glucose (30 mM)-exposed neuro2a (N2A) cells...
May 11, 2017: Journal of Nutritional Biochemistry
https://www.readbyqxmd.com/read/28516115/a-modified-chromogenic-assay-for-determination-of-the-ratio-of-free-intracellular-nad-nadh-in-streptococcus-mutans
#17
Jonathon L Baker, Roberta C Faustoferri, Robert G Quivey
Nicotinamide adenine dinucleotide is a coenzyme present in all kingdoms of life and exists in two forms: oxidized (NAD(+)) and reduced (NADH). NAD(H) is involved in a multitude of essential metabolic redox reactions, providing oxidizing or reducing equivalents. The ratio of free intracellular NAD(+)/NADH is fundamentally important in the maintenance of cellular redox homeostasis (Ying, 2008). Various chromogenic cycling assays have been used to determine the ratio of NAD(+)/NADH in both bacterial and mammalian cells for more than forty years (Bernofsky and Swan, 1973; Nisselbaum and Green, 1969)...
August 20, 2016: Bio-protocol
https://www.readbyqxmd.com/read/28514055/caveolin-1-deficiency-induces-premature-senescence-with-mitochondrial-dysfunction
#18
Dong-Min Yu, Seung Hee Jung, Hyoung-Tae An, Sungsoo Lee, Jin Hong, Jun Sub Park, Hyun Lee, Hwayeon Lee, Myeong-Suk Bahn, Hyung Chul Lee, Na-Kyung Han, Jesang Ko, Jae-Seon Lee, Young-Gyu Ko
Paradoxical observations have been made regarding the role of caveolin-1 (Cav-1) during cellular senescence. For example, caveolin-1 deficiency prevents reactive oxygen species-induced cellular senescence despite mitochondrial dysfunction, which leads to senescence. To resolve this paradox, we re-addressed the role of caveolin-1 in cellular senescence in human diploid fibroblasts, A549, HCT116, and Cav-1(-/-) mouse embryonic fibroblasts. Cav-1 deficiency (knockout or knockdown) induced cellular senescence via a p53-p21-dependent pathway, downregulating the expression level of the cardiolipin biosynthesis enzymes and then reducing the content of cardiolipin, a critical lipid for mitochondrial respiration...
May 17, 2017: Aging Cell
https://www.readbyqxmd.com/read/28504706/the-mitochondrial-respiratory-chain-is-essential-for-haematopoietic-stem-cell-function
#19
Elena Ansó, Samuel E Weinberg, Lauren P Diebold, Benjamin J Thompson, Sébastien Malinge, Paul T Schumacker, Xin Liu, Yuannyu Zhang, Zhen Shao, Mya Steadman, Kelly M Marsh, Jian Xu, John D Crispino, Navdeep S Chandel
Adult and fetal haematopoietic stem cells (HSCs) display a glycolytic phenotype, which is required for maintenance of stemness; however, whether mitochondrial respiration is required to maintain HSC function is not known. Here we report that loss of the mitochondrial complex III subunit Rieske iron-sulfur protein (RISP) in fetal mouse HSCs allows them to proliferate but impairs their differentiation, resulting in anaemia and prenatal death. RISP-null fetal HSCs displayed impaired respiration resulting in a decreased NAD(+)/NADH ratio...
June 2017: Nature Cell Biology
https://www.readbyqxmd.com/read/28498799/dietary-luteolin-attenuates-chronic-liver-injury-induced-by-mercuric-chloride-via-the-nrf2-nf-%C3%AE%C2%BAb-p53-signaling-pathway-in-rats
#20
Haili Zhang, Xiao Tan, Daqian Yang, Jingjing Lu, Biying Liu, Ruiqi Baiyun, Zhigang Zhang
Mercury exposure is a common cause of metal poisoning which is biotransformed to highly toxic metabolites thus eliciting biochemical alterations and oxidative stress. Luteolin, a phenolic compound found in many natural products, has multiple biological functions. Our study was aimed to explore the biological effects of luteolin in a liver injury model induced in rats by mercuric chloride (HgCl2). Criteria for injury included liver enzyme, glutathione and malondialdehyde levels, histopathology, TUNEL assay, hepatocyte viability and reactive oxygen species levels...
June 20, 2017: Oncotarget
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