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NADH AND ATP

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https://www.readbyqxmd.com/read/29330287/targeted-akt-inhibition-in-prostate-cancer-cells-and-spheroids-reduces-aerobic-glycolysis-and-generation-of-hyperpolarized-1-13c-lactate
#1
Sui Seng Tee, Izabela Suster, Steven Truong, Sangmoo Jeong, Roozbeh Eskandari, Valentina Di Gialleonardo, Julio A Alvarez, Hannah N Aldeborgh, Kayvan Keshari
The PI3K/AKT/mTOR (PAM) signaling pathway is frequently mutated in prostate cancer. Specific AKT inhibitors are now in advanced clinical trials and this study investigates the effect of MK2206, a non-ATP competitive inhibitor, on the cellular metabolism in the context of prostate cancer. A significant reduction in cell motility and aerobic glycolysis was observed in prostate cancer cells with treatment. These changes were not accompanied by a reduction in the ratio of high-energy phosphates or a change in total protein levels of enzymes (e...
January 12, 2018: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/29303599/proteomic-analysis-of-peroxynitrite-induced-protein-nitration-in-isolated-beef-heart-mitochondria
#2
M Kohutiar, A Eckhardt, I Mikšík, P Šantorová, J Wilhelm
Mitochondria are exposed to reactive nitrogen species under physiological conditions and even more under several pathologic states. In order to reveal the mechanism of these processes we studied the effects of peroxynitrite on isolated beef heart mitochondria in vitro. Peroxynitrite has the potential to nitrate protein tyrosine moieties, break the peptide bond, and eventually release the membrane proteins into the solution. All these effects were found in our experiments. Mitochondrial proteins were resolved by 2D electrophoresis and the protein nitration was detected by immunochemical methods and by nano LC-MS/MS...
January 5, 2018: Physiological Research
https://www.readbyqxmd.com/read/29288336/cytotoxicity-of-propofol-in-human-induced-pluripotent-stem-cell-derived-cardiomyocytes
#3
Koji Kido, Hiroyuki Ito, Yudai Yamamoto, Koshi Makita, Tokujiro Uchida
PURPOSE: Propofol infusion syndrome (PRIS) is a lethal condition caused by propofol overdose. Previous studies suggest that pathophysiological mechanisms underlying PRIS involve mitochondrial dysfunction; however, these mechanisms have not been fully elucidated. This study aimed to establish an experimental model of propofol-induced cytotoxicity using cultured human induced pluripotent stem cell (iPSC)-derived cardiomyocytes to determine the mechanisms behind propofol-induced mitochondrial dysfunction, and to evaluate the protective effects of coenzyme Q10 (CoQ10)...
December 29, 2017: Journal of Anesthesia
https://www.readbyqxmd.com/read/29285300/renal-oncocytoma-characterized-by-the-defective-complex-i-of-the-respiratory-chain-boosts-the-synthesis-of-the-ros-scavenger-glutathione
#4
Gerrit Kürschner, Qingzhou Zhang, Rosanna Clima, Yi Xiao, Jonas Felix Busch, Ergin Kilic, Klaus Jung, Nikolaus Berndt, Sascha Bulik, Hermann-Georg Holzhütter, Giuseppe Gasparre, Marcella Attimonelli, Mohan Babu, David Meierhofer
Renal oncocytomas are rare benign tumors of the kidney and characterized by a deficient complex I (CI) enzyme activity of the oxidative phosphorylation (OXPHOS) system caused by mitochondrial DNA (mtDNA) mutations. Yet, little is known about the underlying molecular mechanisms and alterations of metabolic pathways in this tumor. We compared renal oncocytomas with adjacent matched normal kidney tissues on a global scale by multi-omics approaches, including whole exome sequencing (WES), proteomics, metabolomics, and metabolic pathway simulation...
December 1, 2017: Oncotarget
https://www.readbyqxmd.com/read/29261292/haloacetic-acid-water-disinfection-by-products-affect-pyruvate-dehydrogenase-activity-and-disrupt-cellular-metabolism
#5
Azra Dad, Clara Hyunhee Jeong, Elizabeth D Wagner, Michael J Plewa
The disinfection of drinking water has been a major public health achievement. However, haloacetic acids (HAAs), generated as by-products of water disinfection, are cytotoxic, genotoxic, mutagenic, carcinogenic and teratogenic. Previous studies of monoHAA-induced genotoxicity and cell stress demonstrated that the toxicity was due to inhibition of glyceraldehyde-3-phosphate dehydrogenase (GAPDH) leading to disruption of cellular metabolism and energy homeostasis. DiHAAs and triHAAs are also produced during water disinfection, and whether they share mechanisms of action with monoHAAs is unknown...
December 20, 2017: Environmental Science & Technology
https://www.readbyqxmd.com/read/29245965/the-aldehyde-group-of-gossypol-induces-mitochondrial-apoptosis-via-ros-sirt1-p53-puma-pathway-in-male-germline-stem-cell
#6
Xin He, Chongyang Wu, Yanhua Cui, Haijing Zhu, Zhiming Gao, Bo Li, Jinlian Hua, Baoyu Zhao
As a widely grown economic crop, cotton is the major oil and protein resource for human and livestock. But the highly toxic of gossypol in cottonseed severely restricts its effective utilization, consequently creating huge resource waste. Previous studies have shown the male germline stem cells were the most vulnerable cells in gossypol damages, but the mechanism was still unclear. We found gossypol induced cell viability decline resulted from apoptosis. And the increase of Caspase-9 activity in gossypol treatment hinted the mitochondrial apoptosis...
November 21, 2017: Oncotarget
https://www.readbyqxmd.com/read/29228460/emissive-synthetic-cofactors-enzymatic-interconversions-of-tza-analogues-of-atp-nad-nadh-nadp-and-nadph
#7
Yitzhak Tor, François Hallé, Andrea Fin, Alexander R Rovira
A series of enzymatic transformations, which generate visibly emissive isofunctional cofactors based on an isothiazolo[4,3-d]pyrimidine analogue of adenosine (tzA), is described. Nicotinamide adenylyl transferase condenses nicotinamide mononucleotide and tzATP to yield NtzAD+, which can be enzymatically phosphorylated by NAD+ kinase and ATP or tzATP to the corresponding NtzADP+. The latter can be engaged in NADP-specific coupled enzymatic transformations involving conversion to NtzADPH by glucose-6-phosphate dehydrogenase and reoxidation to NtzADP+ by glutathione reductase...
December 11, 2017: Angewandte Chemie
https://www.readbyqxmd.com/read/29212305/cancer-energy-metabolism-shutting-power-off-cancer-factory
#8
REVIEW
Soo-Youl Kim
In 1923, Dr. Warburg had observed that tumors acidified the Ringer solution when 13 mM glucose was added, which was identified as being due to lactate. When glucose is the only source of nutrient, it can serve for both biosynthesis and energy production. However, a series of studies revealed that the cancer cell consumes glucose for biosynthesis through fermentation, not for energy supply, under physiological conditions. Recently, a new observation was made that there is a metabolic symbiosis in which glycolytic and oxidative tumor cells mutually regulate their energy metabolism...
January 1, 2018: Biomolecules & Therapeutics
https://www.readbyqxmd.com/read/29197713/development-of-a-simultaneous-identification-method-for-13-animal-species-using-two-multiplex-real-time-pcr-assays-and-melting-curve-analysis
#9
Natsumi Ishida, Makoto Sakurada, Hiroshi Kusunoki, Yasuhiro Ueno
We developed a simple and rapid method for animal species identification in the forensic science field based on mitochondrial DNA using two multiplex real-time PCRs and analysis of the resultant SYBR Green I melting curves. This method was designed to identify nine domestic animals simultaneously (dog, cat, rabbit, cattle, pig, chicken, goat, sheep and horse) and four wild animals (deer, raccoon-dog, monkey and bear) by comparing the different melting temperatures of the amplicons produced from samples originating from each species...
November 26, 2017: Legal Medicine
https://www.readbyqxmd.com/read/29189472/sirt2-and-akt-mediate-nad-induced-and-nadh-induced-increases-in-the-intracellular-atp-levels-of-bv2-microglia-under-basal-conditions
#10
Jie Zhang, Caixia Wang, Weihai Ying
NAD replenishment can restore ATP levels and rescue premature aging in Cockayne syndrome mice. However, there has been no mechanistic study regarding the effects of NAD and NADH on intracellular ATP levels under basal conditions. In our current study, we used BV2 microglia to test our hypothesis that NAD and NADH can increase intracellular ATP levels under basal conditions. We found that both NAD and NADH significantly increased the intracellular ATP levels of BV2 microglia, which were attenuated by SIRT2 siRNA, the SIRT2 inhibitor AGK2, and the phosphatidylinositol 3-kinase/Akt inhibitor LY294002...
November 20, 2017: Neuroreport
https://www.readbyqxmd.com/read/29181726/the-inhibition-of-polyamine-biosynthesis-weakens-the-drought-tolerance-in-white-clover-trifolium-repens-associated-with-the-alteration-of-extensive-proteins
#11
Zhou Li, Yan Zhang, Dandan Peng, Yan Peng, Xinquan Zhang, Xiao Ma, Linkai Huang, Yanhong Yan
Changes of endogenous polyamine (PA) levels could be a key adaptive response to drought in plants. White clover pretreated with or without dicyclohexylamine (DCHA), an inhibitor of PA biosynthesis, was subjected to drought stress induced by 18% polyethylene glycol 6000 for 8 days in controlled growth chambers. Results showed that drought stress significantly increased endogenous PA content, whereas DCHA significantly decreased PA accumulation under drought stress. The attenuate PA biosynthesis was unfavorable for plant growth and drought tolerance, as reflected by significantly lower relative water content, relative growth rate, instantaneous water use efficiency, and cell membrane stability in leaves in response to drought...
November 28, 2017: Protoplasma
https://www.readbyqxmd.com/read/29177661/bacterial-hsp90-atpase-assays
#12
Joel R Hoskins, Sue Wickner, Shannon M Doyle
Bacterial Hsp90 is an ATP-dependent molecular chaperone involved in protein remodeling and activation. The E. coli Hsp90, Hsp90Ec, collaborates in protein remodeling with another ATP-dependent chaperone, DnaK, the E. coli Hsp70. Both Hsp90Ec and DnaK hydrolyze ATP and client (substrate) proteins stimulate the hydrolysis. Additionally, ATP hydrolysis by the combination of Hsp90Ec and DnaK is synergistically stimulated in the presence of client (substrate). Here, we describe two steady-state ATPase assays used to monitor ATP hydrolysis by Hsp90Ec and DnaK as well as the synergistic stimulation of ATP hydrolysis by the combination of Hsp90Ec and DnaK in the presence of a client (substrate)...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29158198/vitamin-c-exerts-novel-protective-effects-against-cadmium-toxicity-in-mouse-spermatozoa-by-inducing-the-dephosphorylation-of-dihydrolipoamide-dehydrogenase
#13
Lirui Wang, Peifei Li, Yi Wen, Qiangzhen Yang, Linqing Zhen, Jieli Fu, Yuhua Li, Sisi Li, Chengxiao Han, Xinhong Li
Cadmium (Cd) has been reported to inhibit mouse sperm motility by inducing the tyrosine phosphorylation of dihydrolipoamide dehydrogenase (DLD). This study aimed to assess the potential effects of vitamin C (Vc) on ameliorating Cd-induced tyrosine phosphorylation of DLD and the specific underlying mechanism. Vc induced the dephosphorylation of DLD or inhibited the tyrosine phosphorylation of DLD. Accordingly, DLD activity, nicotinamide adenine dinucleotide hydrogen (NADH) levels, ATP levels and motility parameters were all restored to normal levels by Vc...
November 20, 2017: Reproductive Toxicology
https://www.readbyqxmd.com/read/29145079/microbial-transcript-and-metabolome-analysis-uncover-discrepant-metabolic-pathways-in-autotrophic-and-mixotrophic-anammox-consortia
#14
Ying Feng, Yunpeng Zhao, Yongzhao Guo, Sitong Liu
The ability of anammox bacteria to utilize organic matter has drawn extensive attention. However, the metabolic discrepancies between autotrophic and mixotrophic anammox consortia need to be further explored. Here, microbial transcript and metabolomic analysis were conducted for the samples harvested in the reactors and batch assays to investigate the phenotype discrepancies and intrinsic causes in autotrophic and mixotrophic anammox consortia. Results showed that metabolically active community structures did not show significant difference between autotrophic and mixotrophic anammox consortia (C/N = 0...
October 31, 2017: Water Research
https://www.readbyqxmd.com/read/29133414/correlating-kinetic-and-structural-data-on-ubiquinone-binding-and-reduction-by-respiratory-complex-i
#15
Justin G Fedor, Andrew J Y Jones, Andrea Di Luca, Ville R I Kaila, Judy Hirst
Respiratory complex I (NADH:ubiquinone oxidoreductase), one of the largest membrane-bound enzymes in mammalian cells, powers ATP synthesis by using the energy from electron transfer from NADH to ubiquinone-10 to drive protons across the energy-transducing mitochondrial inner membrane. Ubiquinone-10 is extremely hydrophobic, but in complex I the binding site for its redox-active quinone headgroup is ∼20 Å above the membrane surface. Structural data suggest it accesses the site by a narrow channel, long enough to accommodate almost all of its ∼50-Å isoprenoid chain...
November 13, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29123192/targeted-mitochondrial-therapy-using-mitoq-shows-equivalent-renoprotection-to-angiotensin-converting-enzyme-inhibition-but-no-combined-synergy-in-diabetes
#16
Micheal S Ward, Nicole B Flemming, Linda A Gallo, Amelia K Fotheringham, Domenica A McCarthy, Aowen Zhuang, Peter H Tang, Danielle J Borg, Hannah Shaw, Benjamin Harvie, David R Briskey, Llion A Roberts, Manuel R Plan, Michael P Murphy, Mark P Hodson, Josephine M Forbes
Mitochondrial dysfunction is a pathological mediator of diabetic kidney disease (DKD). Our objective was to test the mitochondrially targeted agent, MitoQ, alone and in combination with first line therapy for DKD. Intervention therapies (i) vehicle (D); (ii) MitoQ (DMitoQ;0.6 mg/kg/day); (iii) Ramipril (DRam;3 mg/kg/day) or (iv) combination (DCoAd) were administered to male diabetic db/db mice for 12 weeks (n = 11-13/group). Non-diabetic (C) db/m mice were followed concurrently. No therapy altered glycaemic control or body weight...
November 9, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29122703/improving-metabolic-efficiency-of-the-reverse-beta-oxidation-cycle-by-balancing-redox-cofactor-requirement
#17
Junjun Wu, Xia Zhang, Peng Zhou, Jiaying Huang, Xiudong Xia, Wei Li, Ziyu Zhou, Yue Chen, Yinghao Liu, Mingsheng Dong
Previous studies have made many exciting achievements on pushing the functional reversal of beta-oxidation cycle (r-BOX) to more widespread adoption for synthesis of a wide variety of fuels and chemicals. However, the redox cofactor requirement for the efficient operation of r-BOX remains unclear. In this work, the metabolic efficiency of r-BOX for medium-chain fatty acid (C6-C10, MCFA) production was optimized by redox cofactor engineering. Stoichiometric analysis of the r-BOX pathway and further experimental examination identified NADH as a crucial determinant of r-BOX process yield...
November 6, 2017: Metabolic Engineering
https://www.readbyqxmd.com/read/29122174/differential-gene-expression-profiling-analysis-in-pleurotus-ostreatus-during-interspecific-antagonistic-interactions-with-dichomitus-squalens-and-trametes-versicolor
#18
Zixuan Zhong, Liu Li, Peng Chang, Haiying Xie, Huiting Zhang, Yasuo Igarashi, Nannan Li, Feng Luo
This study provided analysis of differentially expressed genes (DEGs) in Pleurotus ostreatus under the interaction with Dichomitus squalens and Trametes versicolor, which is valuable for exploration on the fungal defence system against stressful condition caused by interspecific antagonistic interaction. Our result showed significant upregulation of abundant defence-related genes encoding laccase, manganese peroxidase, aldo-keto reductase, and glutathione S-transferase, which all play important roles in oxidative stress-resistant response...
December 2017: Fungal Biology
https://www.readbyqxmd.com/read/29112954/metabolic-dynamics-restricted-by-conserved-carriers-jamming-and-feedback
#19
Tetsuhiro S Hatakeyama, Chikara Furusawa
To uncover the processes and mechanisms of cellular physiology, it first necessary to gain an understanding of the underlying metabolic dynamics. Recent studies using a constraint-based approach succeeded in predicting the steady states of cellular metabolic systems by utilizing conserved quantities in the metabolic networks such as carriers such as ATP/ADP as an energy carrier or NADH/NAD+ as a hydrogen carrier. Although such conservation quantities restrict not only the steady state but also the dynamics themselves, the latter aspect has not yet been completely understood...
November 2017: PLoS Computational Biology
https://www.readbyqxmd.com/read/29082074/optical-imaging-for-the-assessment-of-hepatocyte-metabolic-state-in-ischemia-and-reperfusion-injuries
#20
Mette F la Cour, Shima Mehrvar, Joohyun Kim, Alicia Martin, Michael A Zimmerman, Johnny C Hong, Mahsa Ranji
Deterioration in mitochondrial function leads to hepatic ischemia and reperfusion injury (IRI) in liver surgery and transplantation. 3D optical cryoimaging was used to measure the levels of mitochondrial coenzymes NADH and FAD, and their redox ratio (NADH/FAD) gave a quantitative marker for hepatocyte oxidative stress during IRI. Using a rat model, five groups were compared: control, ischemia for 60 or 90 minutes (Isc60, Isc90), ischemia for 60 or 90 minutes followed by reperfusion of 24 hours (IRI60, IRI90)...
October 1, 2017: Biomedical Optics Express
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