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https://www.readbyqxmd.com/read/28102848/statins-in-anthracycline-induced-cardiotoxicity-rac-and-rho-and-the-heartbreakers
#1
REVIEW
Christian Henninger, Gerhard Fritz
Cancer patients receiving anthracycline-based chemotherapy are at risk to develop life-threatening chronic cardiotoxicity with the pathophysiological mechanism of action not fully understood. Besides the most common hypothesis that anthracycline-induced congestive heart failure (CHF) is mainly caused by generation of reactive oxygen species, recent data point to a critical role of topoisomerase II beta (TOP2B), which is a primary target of anthracycline poisoning, in the pathophysiology of CHF. As the use of the only clinically approved cardioprotectant dexrazoxane has been limited by the FDA in 2011, there is an urgent need for alternative cardioprotective measures...
January 19, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28101749/twenty-seven-years-of-cerebral-pyruvate-recycling
#2
Sebastián Cerdán
Cerebral pyruvate recycling is a metabolic pathway deriving carbon skeletons and reducing equivalents from mitochondrial oxaloacetate and malate, to the synthesis of mitochondrial and cytosolic pyruvate, lactate and alanine. The pathway allows both, to provide the tricarboxylic acid cycle with pyruvate molecules produced from alternative substrates to glucose and, to generate reducing equivalents necessary for the operation of NADPH requiring processes. At the cellular level, pyruvate recycling involves the activity of malic enzyme, or the combined activities of phosphoenolpyruvate carboxykinase and pyruvate kinase, as well as of those transporters of the inner mitochondrial membrane exchanging the corresponding intermediates...
January 18, 2017: Neurochemical Research
https://www.readbyqxmd.com/read/28101244/celery-extract-inhibits-mouse-cyp2a5-and-human-cyp2a6-activities-via-different-mechanisms
#3
Xiao Deng, Qianghong Pu, Erhao Wang, Chao Yu
Human cytochrome P450 (CYP) 2A6 participates in the metabolism of nicotine and precarcinogens, thus the deliberate inhibition of CYP2A6 may reduce cigarette consumption and therefore reduce the risk of developing the types of cancer associated with smoking. The inhibitory effects and mechanisms of celery (Apium graveolens) extract on mouse CYP2A5 and human CYP2A6 activity remain unclear. These effects were investigated in mouse and human liver microsomes using coumarin 7-hydroxylation in a probe reaction. Celery extract reduced CYP2A5 and CYP2A6 activities in vitro in a dose-dependent manner...
December 2016: Oncology Letters
https://www.readbyqxmd.com/read/28099419/genomic-deletion-of-malic-enzyme-2-confers-collateral-lethality-in-pancreatic-cancer
#4
Prasenjit Dey, Joelle Baddour, Florian Muller, Chia Chin Wu, Huamin Wang, Wen-Ting Liao, Zangdao Lan, Alina Chen, Tony Gutschner, Yaan Kang, Jason Fleming, Nikunj Satani, Di Zhao, Abhinav Achreja, Lifeng Yang, Jiyoon Lee, Edward Chang, Giannicola Genovese, Andrea Viale, Haoqiang Ying, Giulio Draetta, Anirban Maitra, Y Alan Wang, Deepak Nagrath, Ronald A DePinho
The genome of pancreatic ductal adenocarcinoma (PDAC) frequently contains deletions of tumour suppressor gene loci, most notably SMAD4, which is homozygously deleted in nearly one-third of cases. As loss of neighbouring housekeeping genes can confer collateral lethality, we sought to determine whether loss of the metabolic gene malic enzyme 2 (ME2) in the SMAD4 locus would create cancer-specific metabolic vulnerability upon targeting of its paralogous isoform ME3. The mitochondrial malic enzymes (ME2 and ME3) are oxidative decarboxylases that catalyse the conversion of malate to pyruvate and are essential for NADPH regeneration and reactive oxygen species homeostasis...
January 18, 2017: Nature
https://www.readbyqxmd.com/read/28098862/rhein-suppresses-matrix-metalloproteinase-production-by-regulating-the-rac1-ros-mapk-ap-1-pathway-in-human-ovarian-carcinoma-cells
#5
Guomei Zhou, Fenghui Peng, Yanping Zhong, Yanhua Chen, Min Tang, Danrong Li
Matrix metalloproteinases (MMPs) are a family of calcium-dependent zinc-containing endopeptidases, which play an integral role in migration and invasion of ovarian cancer. Rac1 proteins might mostly influence cell migration and invasion by generating endogenous reactive oxygen species. Therefore, inhibiting MMPs and regulating the Rac1/ROS/MAPK/AP-1 pathway may be a new therapeutic strategy for ovarian cancer. In this study, we found that rhein could suppress the invasion and migration of SKOV3-PM4 cells with characteristics of directional highly lymphatic metastasis...
January 17, 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/28098803/optimization-of-the-production-of-1-phenylethanol-using-enzymes-from-flowers-of-tea-camellia-sinensis-plants
#6
Fang Dong, Ying Zhou, Lanting Zeng, Naoharu Watanabe, Xinguo Su, Ziyin Yang
1-Phenylethanol (1PE) can be used as a fragrance in food flavoring and cosmetic industries and as an intermediate in the pharmaceutical industry. 1PE can be synthesized from acetophenone, and the cost of 1PE is higher than the cost of acetophenone. Therefore, it is important to establish an effective and low-cost approach for producing 1PE. Our previous studies found that tea (Camellia sinensis) flowers, which are an abundant and waste resource, contained enzymes that could transform acetophenone to 1PE. In the present study, we extracted crude enzymes from tea flowers and optimized the production conditions of 1PE using response surface methodology...
January 13, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28098759/reactive-oxygen-species-generated-by-nadph-oxidases-promote-radicle-protrusion-and-root-elongation-during-rice-seed-germination
#7
Wen-Yan Li, Bing-Xian Chen, Zhong-Jian Chen, Yin-Tao Gao, Zhuang Chen, Jun Liu
Seed germination is a complicated biological process that requires regulation through various enzymatic and non-enzymatic mechanisms. Although it has been recognized that reactive oxygen species (ROS) regulate radicle emergence and root elongation in a non-enzymatic manner during dicot seed germination, the role of ROS in monocot seed germination remains unknown. NADPH oxidases (NOXs) are the major ROS producers in plants; however, whether and how NOXs regulate rice seed germination through ROS generation remains unclear...
January 13, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28098182/nephro-toxic-effects-of-intraperitoneally-injected-egcg-in-diabetic-mice-involvement-of-oxidative-stress-inflammation-and-apoptosis
#8
Nora O Abdel Rasheed, Lamiaa A Ahmed, Dalaal M Abdallah, Bahia M El-Sayeh
Epigallocatechin gallate (EGCG) has been studied for its beneficial effects. However, some case reports have associated EGCG supplementation with hepato-toxicity. In the present study, we investigated the possible nephro-toxic effects of EGCG in diabetic mice. Streptozotocin (150 mg/kg, i.p.) was injected in mice for diabetes induction. EGCG (100 mg/kg/day, i.p.) was then given for 4 days. The administration of EGCG to diabetic mice caused 60% mortality with no death recorded in other groups. Blood samples were collected for estimation of serum cystatin C, neutrophil gelatinase-associated lipocalin and blood urea nitrogen...
January 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28097492/activation-of-trpm2-and-trpv1-channels-in-dorsal-root-ganglion-by-nadph-oxidase-and-protein-kinase-c-molecular-pathways-a-patch-clamp-study
#9
Mustafa Nazıroğlu
Despite considerable research, the mechanisms of neuropathic pain induced by excessive oxidative stress production and overload calcium ion (Ca(2+)) entry in dorsal root ganglion (DRG) remain substantially unidentified. The transient receptor potential melastatin 2 (TRPM2) and vanilloid 1 (TRPV1) channels are activated with different stimuli including oxidative stress. TRPM2 and TRPV1 have been shown to be involved in induction of neuropathic pain. However, the activation mechanisms of TRPM2 and TRPV1 via NADPH oxidase and protein kinase C (PKC) pathways are poorly understood...
January 17, 2017: Journal of Molecular Neuroscience: MN
https://www.readbyqxmd.com/read/28096301/phosphoinositol-3-phosphate-acts-as-a-timer-for-reactive-oxygen-species-production-in-the-phagosome
#10
Zhi Min Song, Leïla Bouchab, Elodie Hudik, Romain Le Bars, Oliver Nüsse, Sophie Dupré-Crochet
Production of reactive oxygen species (ROS) in the phagosome by the NADPH oxidase is critical for mammalian immune defense against microbial infections and phosphoinositides are important regulators in this process. Phosphoinositol 3-phosphate (PI(3)P) regulates ROS production at the phagosome via p40(phox) by an unknown mechanism. This study tested the hypothesis that PI(3)P controls ROS production by regulating the presence of p40(phox) and p67(phox) at the phagosomal membrane. Pharmacologic inhibition of PI(3)P synthesis at the phagosome decreased the ROS production both in differentiated PLB-985 cells and human neutrophils...
January 17, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28096195/the-multifunctional-mitochondrial-epac1-controls-myocardial-cell-death
#11
Loubina Fazal, Marion Laudette, Sílvia Paula-Gomes, Sandrine Pons, Caroline Conte, Florence Tortosa, Pierre Sicard, Yannis Sainte-Marie, Malik Bisserier, Olivier Lairez, Alexandre Lucas, Jérôme Roy, Bijan Ghaleh, Jeremy Fauconnier, Jeanne Mialet-Perez, Frank Lezoualc'h
RATIONALE: Although the second messenger cyclic AMP (cAMP) is physiologically beneficial in the heart, it largely contributes to cardiac disease progression when dysregulated. Current evidence suggests that cAMP is produced within mitochondria. However, mitochondrial cAMP signaling and its involvement in cardiac pathophysiology are far from being understood. OBJECTIVE: To investigate the role of mitochondrial exchange protein directly activated by cAMP 1 (MitEpac1) in ischemia/reperfusion (I/R) injury...
January 17, 2017: Circulation Research
https://www.readbyqxmd.com/read/28095923/nadph-oxidase-in-brain-injury-and-neurodegenerative-disorders
#12
REVIEW
Merry W Ma, Jing Wang, Quanguang Zhang, Ruimin Wang, Krishnan M Dhandapani, Ratna K Vadlamudi, Darrell W Brann
Oxidative stress is a common denominator in the pathology of neurodegenerative disorders such as Alzheimer's disease, Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis, and multiple sclerosis, as well as in ischemic and traumatic brain injury. The brain is highly vulnerable to oxidative damage due to its high metabolic demand. However, therapies attempting to scavenge free radicals have shown little success. By shifting the focus to inhibit the generation of damaging free radicals, recent studies have identified NADPH oxidase as a major contributor to disease pathology...
January 17, 2017: Molecular Neurodegeneration
https://www.readbyqxmd.com/read/28095320/lethal-dysregulation-of-energy-metabolism-during-embryonic-vitamin-e-deficiency
#13
Melissa McDougall, Jaewoo Choi, Hye-Kyeong Kim, Gerd Bobe, J Frederik Stevens, Enrique Cadenas, Robert Tanguay, Maret G Traber
Vitamin E (α-tocopherol, VitE) was discovered in 1922 for its role in preventing embryonic mortality. We investigated the underlying mechanisms causing lethality using targeted metabolomics analyses of zebrafish VitE-deficient embryos over five days of development, which coincided with their increased morbidity and mortality. VitE deficiency resulted in peroxidation of docosahexaenoic acid (DHA), depleting DHA-containing phospholipids, especially phosphatidylcholine, which also caused choline depletion. This increased lipid peroxidation also increased NADPH oxidation, which depleted glucose by shunting it to the pentose phosphate pathway...
January 14, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28093652/structural-basis-for-the-isotype-specific-interactions-of-ferredoxin-and-ferredoxin-nadp-oxidoreductase-an-evolutionary-switch-between-photosynthetic-and-heterotrophic-assimilation
#14
Fumio Shinohara, Genji Kurisu, Guy Hanke, Caroline Bowsher, Toshiharu Hase, Yoko Kimata-Ariga
In higher plants, ferredoxin (Fd) and ferredoxin-NADP(+) reductase (FNR) are each present as distinct isoproteins of photosynthetic type (leaf type) and non-photosynthetic type (root type). Root-type Fd and FNR are considered to facilitate the electron transfer from NADPH to Fd in the direction opposite to that occurring in the photosynthetic processes. We previously reported the crystal structure of the electron transfer complex between maize leaf FNR and Fd (leaf FNR:Fd complex), providing insights into the molecular interactions of the two proteins...
January 16, 2017: Photosynthesis Research
https://www.readbyqxmd.com/read/28093607/osmopriming-induced-salt-tolerance-during-seed-germination-of-alfalfa-most-likely-mediates-through-h2o2-signaling-and-upregulation-of-heme-oxygenase
#15
Rayhaneh Amooaghaie, Fatemeh Tabatabaie
The present study showed that osmopriming or pretreatment with low H2O2 doses (2 mM) for 6 h alleviated salt-reduced seed germination. The NADPH oxidase activity was the main source, and superoxide dismutase (SOD) activity might be a secondary source of H2O2 generation during osmopriming or H2O2 pretreatment. Hematin pretreatment similar to osmopriming improved salt-reduced seed germination that was coincident with the enhancement of heme oxygenase (HO) activity. The semi-quantitative RT-PCR confirmed that osmopriming or H2O2 pretreatment was able to upregulate heme oxygenase HO-1 transcription, while the application of N,N-dimethyl thiourea (DMTU as trap of endogenous H2O2) and diphenyleneiodonium (DPI as inhibitor of NADPHox) not only blocked the upregulation of HO but also reversed the osmopriming-induced salt attenuation...
January 16, 2017: Protoplasma
https://www.readbyqxmd.com/read/28093527/human-cystic-fibrosis-macrophages-have-defective-calcium-dependent-protein-kinase-c-activation-of-the-nadph-oxidase-an-effect-augmented-by-burkholderia-cenocepacia
#16
Kaivon Assani, Chandra L Shrestha, Frank Robledo-Avila, Murugesan V Rajaram, Santiago Partida-Sanchez, Larry S Schlesinger, Benjamin T Kopp
Macrophage intracellular pathogen killing is defective in cystic fibrosis (CF), despite abundant production of reactive oxygen species (ROS) in lung tissue. Burkholderia species can cause serious infection in CF and themselves affect key oxidase components in murine non-CF cells. However, it is unknown whether human CF macrophages have an independent defect in the oxidative burst and whether Burkholderia contributes to this defect in terms of assembly of the NADPH oxidase complex and subsequent ROS production...
January 16, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28093500/cytosolic-thioredoxin-reductase-1-is-required-for-correct-disulfide-formation-in-the-er
#17
Greg J Poet, Ojore Bv Oka, Marcel van Lith, Zhenbo Cao, Philip J Robinson, Marie Anne Pringle, Elias Sj Arnér, Neil J Bulleid
Folding of proteins entering the secretory pathway in mammalian cells frequently requires the insertion of disulfide bonds. Disulfide insertion can result in covalent linkages found in the native structure as well as those that are not, so-called non-native disulfides. The pathways for disulfide formation are well characterized, but our understanding of how non-native disulfides are reduced so that the correct or native disulfides can form is poor. Here, we use a novel assay to demonstrate that the reduction in non-native disulfides requires NADPH as the ultimate electron donor, and a robust cytosolic thioredoxin system, driven by thioredoxin reductase 1 (TrxR1 or TXNRD1)...
January 16, 2017: EMBO Journal
https://www.readbyqxmd.com/read/28092678/6-phosphofructo-2-kinase-fructose-2-6-biphosphatase-4-is-essential-for-p53-null-cancer-cells
#18
S Ros, J Flöter, I Kaymak, C Da Costa, A Houddane, S Dubuis, B Griffiths, R Mitter, S Walz, S Blake, A Behrens, K M Brindle, N Zamboni, M H Rider, A Schulze
The bifunctional enzyme 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase-4 (PFKFB4) controls metabolic flux through allosteric regulation of glycolysis. Here we show that p53 regulates the expression of PFKFB4 and that p53-deficient cancer cells are highly dependent on the function of this enzyme. We found that p53 downregulates PFKFB4 expression by binding to its promoter and mediating transcriptional repression via histone deacetylases. Depletion of PFKFB4 from p53-deficient cancer cells increased levels of the allosteric regulator fructose-2,6-bisphosphate, leading to increased glycolytic activity but decreased routing of metabolites through the oxidative arm of the pentose-phosphate pathway...
January 16, 2017: Oncogene
https://www.readbyqxmd.com/read/28092657/lipid-production-in-yarrowia-lipolytica-is-maximized-by-engineering-cytosolic-redox-metabolism
#19
Kangjian Qiao, Thomas M Wasylenko, Kang Zhou, Peng Xu, Gregory Stephanopoulos
Microbial factories have been engineered to produce lipids from carbohydrate feedstocks for production of biofuels and oleochemicals. However, even the best yields obtained to date are insufficient for commercial lipid production. To maximize the capture of electrons generated from substrate catabolism and thus increase substrate-to-product yields, we engineered 13 strains of Yarrowia lipolytica with synthetic pathways converting glycolytic NADH into the lipid biosynthetic precursors NADPH or acetyl-CoA. A quantitative model was established and identified the yield of the lipid pathway as a crucial determinant of overall process yield...
January 16, 2017: Nature Biotechnology
https://www.readbyqxmd.com/read/28091926/effect-of-hypotensive-drugs-on-dynamics-of-nitroxide-producing-renal-function-in-rats-with-nephrogenic-hypertension
#20
E V Eliseeva, E F Romanchenko, I V Dyuizen, A V Tyrtyshnikova, Yu I Pigolkin
An original model of nephrogenic hypertension in rats was used for histochemical mapping of NADPH diaphorase (NO synthase) in various renal segments to examine the effect of hypotensive drugs furosemide, bendazol, and clonidine on the time course of nitroxide production in the kidneys. In various nephron segments, these drugs modulated NO synthesis in different ways. Clonidine induced a stable up-regulation of NO synthesis, which can maintain active vasodilation and gradually diminish the rennin production...
January 2017: Bulletin of Experimental Biology and Medicine
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