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https://www.readbyqxmd.com/read/29242378/flavodiiron-protein-substitutes-for-cyclic-electron-flow-without-competing-co2-assimilation
#1
Shinya Wada, Hiroshi Yamamoto, Yuji Suzuki, Wataru Yamori, Toshiharu Shikanai, Amane Makino
Flavodiiron protein (FLV) mediates photoreduction of O2 to H2O. It is conserved from cyanobacteria to gymnosperms but not in angiosperms. The introduction of a moss (Physcomitrella patens) FLV (PpFLV) gene into Arabidopsis made photosystem I (PSI) resistant to fluctuating light. Here, we used the same strategy with three rice genotypes. PpFLV in the wild-type rice background functioned as an efficient PSI electron sink and increased resistance to PSI photodamage under fluctuating light. The introduction of PpFLV into the PGR5-RNAi mutant (defective in PROTON GRADIENT REGULATION 5 (PGR5)-dependent cyclic electron transport around PSI: CET-PSI), the crr6 mutant (defective in chloroplast NAD(P)H-dehydrogenase like complex (NDH)-dependent CET-PSI), and the PGR5-RNAi crr6 double mutant (double defective in CET-PSI activity) alleviated PSI photodamage under fluctuating light...
December 14, 2017: Plant Physiology
https://www.readbyqxmd.com/read/29242061/phosphorylation-of-ser-525-in-%C3%AE-pix-impairs-nox1-activating-ability-in-caco-2%C3%A2-cells
#2
Yuuki Kaito, Ryosuke Kataoka, Tatsuya Mihara, Kento Takechi, Akira Takahira, Shuhei Watanabe, Fei Han, Minoru Tamura
βPix activates Nox1, an O2--generating NADPH oxidase, through Rac activation. In this study, we found that S525E mutation of βPix eliminated its Nox1-activating ability in transfected Caco-2 cells. Unexpectedly, affinity for Rac was not diminished but rather enhanced by S525E mutation, and guanine nucleotide exchange factor (GEF) activity was not altered. The N-terminal fragment (amino acids 1-400) showed similar Rac-binding and GEF activity to wild-type βPix. In contrast, the C-terminal fragment (amino acids 408-646) had higher Rac-binding activity, particularly for Rac-GTP, than wild-type βPix, and showed no GEF activity...
December 11, 2017: Archives of Biochemistry and Biophysics
https://www.readbyqxmd.com/read/29237157/hypoxia-accelerates-aggressiveness-of-hepatocellular-carcinoma-cells-involving-oxidative-stress-epithelial-mesenchymal-transition-and-non-canonical-hedgehog-signaling
#3
Zhikui Liu, Kangsheng Tu, Yufeng Wang, Bowen Yao, Qing Li, Liang Wang, Changwei Dou, Qingguang Liu, Xin Zheng
BACKGROUND/AIMS: Hypoxic microenvironment, a common feature of hepatocellular carcinoma (HCC), can induce HIF-1α expression and promote the epithelial-mesenchymal transition (EMT) and invasion of cancer cells. However, the underlying molecular mechanisms have not fully elucidated. METHODS: HCC cells were cultured under controlled hypoxia conditions or normoxic conditions. Transwell assays were used to examine the migration and invasion capacity. HIF-1α siRNA, cyclopamine (a SMO antagonist) and GLI1 siRNA were used to inhibit HIF-1α transcription or Hh signaling activation...
December 11, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29236702/oral-nicotine-aggravates-endothelial-dysfunction-and-vascular-inflammation-in-diet-induced-obese-rats-role-of-macrophage-tnf%C3%AE
#4
Chang Liu, Ming-Sheng Zhou, Yao Li, Aimei Wang, Kiranmai Chadipiralla, Runxia Tian, Leopoldo Raij
Obesity and cigarette smoke are major cardiovascular (CV) risk factors and, when coexisting in the same individuals, have additive/synergistic effects upon CVD. We studied the mechanisms involved in nicotine enhancement of CVD in Sprague Dawley rats with diet-induced obesity. The rats were fed either a high fat (HFD) or normal rat chow diet with or without nicotine (100 mg/L in drinking water) for 20 weeks. HFD rats developed central obesity, increased systolic blood pressure (SBP), aortic superoxide (O2-) production, and impaired endothelial nitric oxide synthase (eNOS) and endothelium-dependent relaxation to acetylcholine (EDR)...
2017: PloS One
https://www.readbyqxmd.com/read/29234237/expression-purification-and-characterization-of-r-sulfolactate-dehydrogenase-comc-from-the-rumen-methanogen-methanobrevibacter-millerae-sm9
#5
Yanli Zhang, Linley R Schofield, Carrie Sang, Debjit Dey, Ron S Ronimus
(R)-Sulfolactate dehydrogenase (EC 1.1.1.337), termed ComC, is a member of an NADH/NADPH-dependent oxidoreductase family of enzymes that catalyze the interconversion of 2-hydroxyacids into their corresponding 2-oxoacids. The ComC reaction is reversible and in the biosynthetic direction causes the conversion of (R)-sulfolactate to sulfopyruvate in the production of coenzyme M (2-mercaptoethanesulfonic acid). Coenzyme M is an essential cofactor required for the production of methane by the methyl-coenzyme M reductase complex...
2017: Archaea: An International Microbiological Journal
https://www.readbyqxmd.com/read/29233819/characterization-of-interactions-among-cyp1a2-cyp2b4-and-nadph-cytochrome-p450-reductase-identification-of-specific-protein-complexes
#6
John Patrick Connick, James R Reed, Wayne L Backes
Cytochromes P450 catalyze oxygenation reactions via interactions with their redox partners. However, other proteins, particularly other P450s, also have been shown to form complexes that modulate P450 function. Previous studies showed that CYP1A2 and CYP2B4 form a complex when reconstituted into phospholipid vesicles; however, details of the interactions among the P450s and NADPH-cytochrome P450 reductase have not been fully characterized. The goal of this study was to examine P450 complex formation in living cells, using bioluminescence resonance energy transfer (BRET)...
December 12, 2017: Drug Metabolism and Disposition: the Biological Fate of Chemicals
https://www.readbyqxmd.com/read/29233818/importance-of-the-unstirred-water-layer-and-hepatocyte-membrane-integrity-in-vitro-for-quantification-of-intrinsic-metabolic-clearance
#7
Francesca Leanne Wood, James Brian Houston, David Hallifax
Prediction of clearance - a vital component of drug discovery - remains in need of improvement and, in particular, requires more incisive assessment of mechanistic methodology in vitro, according to a number of recent reports. Although isolated hepatocytes have become an irreplaceable standard system for measurement of intrinsic hepatic clearance mediated by active uptake transport and metabolism, lack of prediction reliability appears to reflect a lack of methodological validation, especially for highly cleared drugs, as we have previously shown...
December 12, 2017: Drug Metabolism and Disposition: the Biological Fate of Chemicals
https://www.readbyqxmd.com/read/29233792/n-acetylcysteine-supplementation-increases-exercise-performance-and-reduces-oxidative-stress-only-in-individuals-with-low-levels-of-glutathione
#8
Vassilis Paschalis, Anastasios A Theodorou, Nikos V Margaritelis, Antonios Kyparos, Michalis G Nikolaidis
Most of the evidence indicates that chronic antioxidant supplementation induces negative effects in healthy individuals. However, it is currently unknown whether specific redox deficiencies exist and whether targeted antioxidant interventions in deficient individuals can induce positive effects. We hypothesized that the effectiveness of antioxidant supplements to decrease oxidative stress and promote exercise performance depends on the redox status of the individuals that receive the antioxidant treatment. To this aim, we investigated whether N-acetylcysteine (NAC) supplementation would enhance exercise performance by increasing glutathione concentration and by reducing oxidative stress only in individuals with low resting levels of glutathione...
December 9, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/29232638/engineering-a-self-sufficient-mycobacterium-tuberculosis-cyp130-by-gene-fusion-with-the-reductase-domain-of-cyp102a1-from-bacillus-megaterium
#9
Sandra Ortega Ugalde, Rosa A Luirink, Daan P Geerke, Nico P E Vermeulen, Wilbert Bitter, Jan N M Commandeur
CYP130 belongs to the subset of cytochrome P450s from Mycobacterium tuberculosis (Mtb) that have been structurally characterized. Despite several efforts for its functional characterization, CYP130 is still considered an orphan enzyme for which no endogenous or exogenous substrate has been identified. In addition, functional redox-partners for CYP130 have not been clearly established yet, hampering the elucidation of its physiological role. In the present study, a catalytically active fusion protein involving CYP130 and the NADPH reductase-domain of CYP102A1 from Bacillus megaterium was created...
December 7, 2017: Journal of Inorganic Biochemistry
https://www.readbyqxmd.com/read/29230270/activation-of-nlrp3-inflammasome-by-advanced-glycation-end-products-promotes-pancreatic-islet-damage
#10
Xiang Kong, Ai-Ling Lu, Xin-Ming Yao, Qiang Hua, Xiao-Yong Li, Li Qin, Hong-Mei Zhang, Guang-Xun Meng, Qing Su
Accumulation of advanced glycation end products (AGEs) contributes to ageing and age-related diseases, especially type 2 diabetes. The NLRP3 inflammasome, as a vital component of the innate immune system, is implicated in the pathogenesis of type 2 diabetes. However, the role of the NLRP3 inflammasome in AGE-induced pancreatic islet damage remains largely unclear. Results showed that administration of AGEs (120 mg/kg for 6 weeks) in C57BL/6J mice induced an abnormal response to glucose (as measured by glucose tolerance and insulin release), pancreatic β-cell ultrastructural lesion, and cell death...
2017: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/29230018/a-pck1-directed-glycogen-metabolic-program-regulates-formation-and-maintenance-of-memory-cd8-t-cells
#11
Ruihua Ma, Tiantian Ji, Huafeng Zhang, Wenqian Dong, Xinfeng Chen, Pingwei Xu, Degao Chen, Xiaoyu Liang, Xiaonan Yin, Yuying Liu, Jingwei Ma, Ke Tang, Yi Zhang, Yue'e Peng, Jinzhi Lu, Yi Zhang, Xiaofeng Qin, Xuetao Cao, Yonghong Wan, Bo Huang
CD8+ memory T (Tm) cells are fundamental for protective immunity against infections and cancers 1-5 . Metabolic activities are crucial in controlling memory T-cell homeostasis, but mechanisms linking metabolic signals to memory formation and survival remain elusive. Here we show that CD8+ Tm cells markedly upregulate cytosolic phosphoenolpyruvate carboxykinase (Pck1), the hub molecule regulating glycolysis, tricarboxylic acid cycle and gluconeogenesis, to increase glycogenesis via gluconeogenesis. The resultant glycogen is then channelled to glycogenolysis to generate glucose-6-phosphate and the subsequent pentose phosphate pathway (PPP) that generates abundant NADPH, ensuring high levels of reduced glutathione in Tm cells...
December 11, 2017: Nature Cell Biology
https://www.readbyqxmd.com/read/29229746/inhibition-of-nadph-oxidase-dependent-oxidative-stress-in-the-rostral-ventrolateral-medulla-mediates-the-antihypertensive-effects-of-acupuncture-in-spontaneously-hypertensive-rats
#12
Xue-Rui Wang, Jing-Wen Yang, Cai-Shuo Ji, Xiang-Hong Zeng, Guang-Xia Shi, Marc Fisher, Cun-Zhi Liu
Oxidative stress in the rostral ventrolateral medulla (RVLM), where the sympathetic nervous control center is located, contributes to neural mechanisms of hypertension. Acupuncture was previously reported to favorably affect high blood pressure. However, little is known about the effect of acupuncture on oxidative stress-modulated mechanisms in hypertension. This study was designed to evaluate the hypothesis that acupuncture exerts an antihypertensive effect via ameliorating oxidative stress and the redox-sensitive pathway in the RVLM of spontaneously hypertensive rats...
December 11, 2017: Hypertension
https://www.readbyqxmd.com/read/29229611/opposing-actions-of-fibroblast-and-cardiomyocyte-smad3-signaling-in-the-infarcted-myocardium
#13
Ping Kong, Arti V Shinde, Ya Su, Ilaria Russo, Bijun Chen, Amit Saxena, Simon J Conway, Jonathan M Graff, Nikolaos G Frangogiannis
Background -Transforming Growth Factor (TGF)-βs regulate a wide range of cellular responses by activating Smad-dependent and Smad-independent cascades. In the infarcted heart, Smad3 signaling is activated in both cardiomyocytes and interstitial cells. We hypothesized that cell-specific actions of Smad3 regulate repair and remodeling in the infarcted myocardium. Methods -In order to dissect cell-specific Smad3 actions in myocardial infarction, we generated mice with Smad3 loss in activated fibroblasts, or in cardiomyocytes...
December 11, 2017: Circulation
https://www.readbyqxmd.com/read/29228832/nadph-oxidase-4-mediates-ros-production-in-radiation-induced-senescent-cells-and-promotes-migration-of-inflammatory-cells
#14
Yuri Sakai, Tohru Yamamori, Yoji Yoshikawa, Tomoki Bo, Motofumi Suzuki, Kumiko Yamamoto, Tetsuro Ago, Osamu Inanami
Excessive DNA damage induced by ionizing radiation (IR) to normal tissue cells is known to trigger cellular senescence, a process termed stress-induced premature senescence (SIPS). SIPS is often accompanied by the production of reactive oxygen species (ROS), and this is reported to be important for the initiation and maintenance of SIPS. However, the source of ROS during SIPS after IR and their significance in radiation-induced normal tissue damage remain elusive. In the present study, we tested the hypothesis that the NADPH oxidase (NOX) family of proteins mediates ROS production in SIPS-induced cells after IR and plays a role in SIPS-associated biological events...
December 12, 2017: Free Radical Research
https://www.readbyqxmd.com/read/29228786/oxidative-stress-induces-disruption-of-the-axon-initial-segment
#15
Kareem Clark, Brooke A Sword, Jeffrey L Dupree
The axon initial segment (AIS), the domain responsible for action potential initiation and maintenance of neuronal polarity, is targeted for disruption in a variety of central nervous system pathological insults. Previous work in our laboratory implicates oxidative stress as a potential mediator of structural AIS alterations in two separate mouse models of central nervous system inflammation, as these effects were attenuated following reactive oxygen species scavenging and NADPH oxidase-2 ablation. While these studies suggest a role for oxidative stress in modulation of the AIS, the direct effects of reactive oxygen and nitrogen species (ROS/RNS) on the stability of this domain remain unclear...
November 2017: ASN Neuro
https://www.readbyqxmd.com/read/29228460/emissive-synthetic-cofactors-enzymatic-interconversions-of-tza-analogues-of-atp-nad-nadh-nadp-and-nadph
#16
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/29228045/mycobacterial-infection-induces-higher-interleukin-1%C3%AE-and-dysregulated-lung-inflammation-in-mice-with-defective-leukocyte-nadph-oxidase
#17
Wen-Cheng Chao, Chia-Liang Yen, Cheng-Yuan Hsieh, Ya-Fang Huang, Yau-Lin Tseng, Peter Andrija Nigrovic, Chi-Chang Shieh
Granulomatous inflammation causes severe tissue damage in mycobacterial infection while redox status was reported to be crucial in the granulomatous inflammation. Here, we used a NADPH oxidase 2 (NOX2)-deficient mice (Ncf1-/-) to investigate the role of leukocyte-produced reactive oxygen species (ROS) in mycobacterium-induced granulomatous inflammation. We found poorly controlled mycobacterial proliferation, significant body weight loss, and a high mortality rate after M. marinum infection in Ncf1-/- mice. Moreover, we noticed loose and neutrophilic granulomas and higher levels of interleukin (IL)-1β and neutrophil chemokines in Ncf1-/- mice when compared with those in wild type mice...
2017: PloS One
https://www.readbyqxmd.com/read/29225823/human-mitochondrial-mthfd2-is-a-dual-redox-cofactor-specific-methylenetetrahydrofolate-dehydrogenase-methenyltetrahydrofolate-cyclohydrolase
#18
Minhye Shin, Jessica Momb, Dean R Appling
Background: Folate-dependent one-carbon metabolism provides one-carbon units for several biological processes. This pathway is highly compartmentalized in eukaryotes, with the mitochondrial pathway producing formate for use in cytoplasmic processes. The mitochondrial enzyme MTHFD2 has been reported to use NAD+ as a cofactor while the isozyme MTHFD2L utilizes NAD+ or NADP+ at physiologically relevant conditions. Because MTHFD2 is highly expressed in many cancer types, we sought to determine the cofactor preference of this enzyme...
2017: Cancer & Metabolism
https://www.readbyqxmd.com/read/29224355/structural-features-and-domain-movements-controlling-substrate-binding-and-cofactor-specificity-in-class-ii-hmg-coa-reductase
#19
Bradley R Miller, Yan Kung
The key mevalonate pathway enzyme 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase (HMGR) uses the cofactor NAD(P)H to reduce HMG-CoA to mevalonate in the production of countless metabolites and natural products. Although HMGR inhibition by statin drugs is well understood, several mechanistic details of HMGR catalysis remain unresolved, and the structural basis for the wide range in cofactor specificity for either NADH or NADPH among HMGRs from different organisms is also unknown. Here, we present crystal structures of HMGR from Streptococcus pneumoniae (SpHMGR) alongside kinetic data on the enzyme's cofactor preferences...
December 11, 2017: Biochemistry
https://www.readbyqxmd.com/read/29223502/hydroxyl-radical-production-via-nadph-oxidase-in-rat-striatum-due-to-carbon-monoxide-poisoning
#20
Shuichi Hara, Masamune Kobayashi, Fumi Kuriiwa, Kazuya Ikematsu, Hajime Mizukami
Severe poisoning induced by carbon monoxide (CO) at 3000ppm, but not 1000ppm, enhances hydroxyl radical (OH) production in rat striatum, which is greatly susceptible to inhibitors of NADPH oxidase (NOX), including diphenyleneiodonium (DPI), but not xanthine oxidase. The quantitative real-time PCR confirmed the previous microarray finding that CO at 3000ppm, but not 1000ppm, enhanced mRNA expression of dual oxidase 2 (DUOX2), but not DUOX1, in rat striatum, both of which are NOX family members producing reactive oxygen species...
December 6, 2017: Toxicology
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