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https://www.readbyqxmd.com/read/28645576/mechanisms-of-hepatocellular-toxicity-associated-with-new-psychoactive-synthetic-cathinones
#1
Dino Luethi, Matthias E Liechti, Stephan Krähenbühl
Synthetic cathinones are a new class of psychostimulant substances. Rarely, they can cause liver injury but associated mechanisms are not completely elucidated. In order to increase our knowledge about mechanisms of hepatotoxicity, we investigated the effect of five frequently used cathinones on two human cell lines. Bupropion was included as structurally related drug used therapeutically. In HepG2 cells, bupropion, MDPV, mephedrone and naphyrone depleted the cellular ATP content at lower concentrations (0...
June 20, 2017: Toxicology
https://www.readbyqxmd.com/read/28639457/glyoxal-toxicity-in-isolated-rat-liver-mitochondria
#2
M Goudarzi, H Kalantari, M Rezaei
Glyoxal is a physiological metabolite formed by lipid peroxidation, ascorbate autoxidation, oxidative degradation of glucose, and degradation of glycated proteins. Glyoxal has been linked to oxidative stress and can cause a number of cellular damages, including covalent modification of amino and thiol groups of proteins to form advanced glycation end products. However, the mechanism of glyoxal toxicity has not been fully understood. In this study, we have focused on glyoxal toxicity in isolated rat liver mitochondria...
January 1, 2017: Human & Experimental Toxicology
https://www.readbyqxmd.com/read/28609610/an-rna-aptamer-capable-of-forming-hydrogel-by-self-assembly
#3
Zhen Huang, Gagan N Kangovi, Wei Wen, Sangwoo Lee, Li Niu
Hydrogels are supramolecular assemblies with both solute transport properties like liquids and mechanical properties like elastomers. To date, every type of biomolecules, except ribonucleic acid (RNA), are capable of forming hydrogel. Here we report an RNA that forms hydrogel by self-assembly. This RNA is originally identified by systematic evolution of ligands by exponential enrichment (SELEX) to enhance the activity of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors as a potential RNA drug for treatment of cognitive disorders...
June 13, 2017: Biomacromolecules
https://www.readbyqxmd.com/read/28605655/aluminum-chloride-caused-liver-dysfunction-and-mitochondrial-energy-metabolism-disorder-in-rat
#4
Feibo Xu, Yanfen Liu, Hansong Zhao, Kaiyuan Yu, Miao Song, Yanzhu Zhu, Yanfei Li
Aluminum (Al) is known to exert hepatotoxicity. However, the mechanisms mostly are unclear. Liver is a metabolism organ that maintains the energy level and structural stability of body, mitochondria are the main sites of energy metabolism, thus, we hypothesized that mitochondrial energy metabolism disorder contributes to liver dysfunction in aluminum chloride (AlCl3) treatment rat. To verify the hypothesis, forty male Wistar rats were randomly allocated and orally exposed to 0, 64mg/kg, 128mg/kg and 256mg/kg body weight AlCl3 in drinking water for 120days, respectively...
April 20, 2017: Journal of Inorganic Biochemistry
https://www.readbyqxmd.com/read/28595160/redox-signaling-during-hypoxia-in-mammalian-cells
#5
REVIEW
Kimberly A Smith, Gregory B Waypa, Paul T Schumacker
Hypoxia triggers a wide range of protective responses in mammalian cells, which are mediated through transcriptional and post-translational mechanisms. Redox signaling in cells by reactive oxygen species (ROS) such as hydrogen peroxide (H2O2) occurs through the reversible oxidation of cysteine thiol groups, resulting in structural modifications that can change protein function profoundly. Mitochondria are an important source of ROS generation, and studies reveal that superoxide generation by the electron transport chain increases during hypoxia...
May 31, 2017: Redox Biology
https://www.readbyqxmd.com/read/28593900/phellinus-rimosus-improves-mitochondrial-energy-status-and-attenuates-nephrotoxicity-in-diabetic-rats
#6
K A Rony, T A Ajith, Tony A Kuttikadan, R Blaze, K K Janardhanan
BACKGROUND: Mitochondrial dysfunction and increase in reactive oxygen species during diabetes can lead to pathological consequences in kidneys. The present study was aimed to investigate the effect of Phellinus rimosus in the streptozotocin (STZ)-induced diabetic rat renal mitochondria and the possible mechanism of protection. METHODS: Phellinus rimosus (50 and 250 mg/kg, p.o) was treated after inducing diabetes by STZ (45 mg/kg, i.p) in rats. The serum samples were subjected to creatinine and urea estimation...
April 7, 2017: Journal of Basic and Clinical Physiology and Pharmacology
https://www.readbyqxmd.com/read/28589520/role-of-mitochondria-in-methamphetamine-induced-dopaminergic-neurotoxicity-involvement-in-oxidative-stress-neuroinflammation-and-pro-apoptosis-a-review
#7
Eun-Joo Shin, Hai-Quyen Tran, Phuong-Tram Nguyen, Ji Hoon Jeong, Seung-Yeol Nah, Choon-Gon Jang, Toshitaka Nabeshima, Hyoung-Chun Kim
Methamphetamine (MA), an amphetamine-type psychostimulant, is associated with dopaminergic toxicity and has a high abuse potential. Numerous in vivo and in vitro studies have suggested that impaired mitochondria are critical in dopaminergic toxicity induced by MA. Mitochondria are important energy-producing organelles with dynamic nature. Evidence indicated that exposure to MA can disturb mitochondrial energetic metabolism by inhibiting the Krebs cycle and electron transport chain. Alterations in mitochondrial dynamic processes, including mitochondrial biogenesis, mitophagy, and fusion/fission, have recently been shown to contribute to dopaminergic toxicity induced by MA...
June 7, 2017: Neurochemical Research
https://www.readbyqxmd.com/read/28578275/mitochondria-meditated-pathways-of-organ-failure-upon-inflammation
#8
REVIEW
Andrey V Kozlov, Jack R Lancaster, Andras T Meszaros, Adelheid Weidinger
Liver failure induced by systemic inflammatory response (SIRS) is often associated with mitochondrial dysfunction but the mechanism linking SIRS and mitochondria-mediated liver failure is still a matter of discussion. Current hypotheses suggest that causative events could be a drop in ATP synthesis, opening of mitochondrial permeability transition pore, specific changes in mitochondrial morphology, impaired Ca(2+) uptake, generation of mitochondrial reactive oxygen species (mtROS), turnover of mitochondria and imbalance in electron supply to the respiratory chain...
May 25, 2017: Redox Biology
https://www.readbyqxmd.com/read/28560849/transcription-factors-cep-1-p53-and-ceh-23-collaborate-with-aak-2-ampk-to-modulate-longevity-in-caenorhabditis-elegans
#9
Hsin-Wen Chang, Steve Pisano, Amaresh Chaturbedi, Jennifer Chen, Sarah Gordon, Aiswarya Baruah, Siu Sylvia Lee
A decline in mitochondrial electron transport chain (ETC) function has long been implicated in aging and various diseases. Recently, moderate mitochondrial ETC dysfunction has been found to prolong lifespan in diverse organisms, suggesting a conserved and complex role of mitochondria in longevity determination. Several nuclear transcription factors have been demonstrated to mediate the lifespan extension effect associated with partial impairment of the ETC, suggesting that compensatory transcriptional response to be crucial...
May 30, 2017: Aging Cell
https://www.readbyqxmd.com/read/28551798/mitochondrial-proton-leak-plays-a-critical-role-in-pathogenesis-of-cardiovascular-diseases
#10
Jiali Cheng, Gayani Nanayakkara, Ying Shao, Ramon Cueto, Luqiao Wang, William Y Yang, Ye Tian, Hong Wang, Xiaofeng Yang
Mitochondrial proton leak is the principal mechanism that incompletely couples substrate oxygen to ATP generation. This chapter briefly addresses the recent progress made in understanding the role of proton leak in the pathogenesis of cardiovascular diseases. Majority of the proton conductance is mediated by uncoupling proteins (UCPs) located in the mitochondrial inner membrane. It is evident that the proton leak and reactive oxygen species (ROS) generated from electron transport chain (ETC) in mitochondria are linked to each other...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28546431/disruption-of-mitochondrial-electron-transport-chain-function-potentiates-the-pro-apoptotic-effects-of-mapk-inhibition
#11
Andrew P Trotta, Jesse D Gelles, Madhavika N Serasinghe, Patrick Loi, Jack L Arbiser, Jerry E Chipuk
The mitochondrial network is a major site of ATP production through the coupled integration of the electron transport chain (ETC) with oxidative phosphorylation. In melanoma, arising from the Val600Glu mutation in the kinase v-RAF murine sarcoma viral oncogene homolog B (BRAFV600E), oncogenic signaling enhances glucose-dependent metabolism, while reducing mitochondrial ATP production. Likewise, when BRAFV600E is pharmacologically inhibited by targeted therapies (e.g. PLX-4032/Vemurafenib), glucose metabolism is reduced and cells increase mitochondrial ATP production to sustain survival...
May 25, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28545499/pre-silencing-of-genes-involved-in-the-electron-transport-chain-etc-pathway-is-associated-with-responsiveness-to-abatacept-in-rheumatoid-arthritis
#12
C Derambure, G Dzangue-Tchoupou, C Berard, N Vergne, M Hiron, M A D'Agostino, P Musette, O Vittecoq, T Lequerré
BACKGROUND: In the current context of personalized medicine, one of the major challenges in the management of rheumatoid arthritis (RA) is to identify biomarkers that predict drug responsiveness. From the European APPRAISE trial, our main objective was to identify a gene expression profile associated with responsiveness to abatacept (ABA) + methotrexate (MTX) and to understand the involvement of this signature in the pathophysiology of RA. METHODS: Whole human genome microarrays (4 × 44 K) were performed from a first subset of 36 patients with RA...
May 25, 2017: Arthritis Research & Therapy
https://www.readbyqxmd.com/read/28544760/a-novel-pattern-of-yolk-processing-in-developing-snake-eggs-colubridae-lampropeltini-and-its-functional-and-evolutionary-implications
#13
Kathryn G Powers, Daniel G Blackburn
Early amniotic vertebrates evolved large-yolked eggs that permitted production of well-developed, terrestrial hatchlings. This reproductive pattern required new mechanisms for cellularizing the yolk and mobilizing it for embryonic use. In birds, cells that line the yolk sac cavity phagocytose and digest the yolk material, a pattern that is commonly assumed to be universal among oviparous amniotes. However, recent evidence challenges the assumption that all squamate reptiles conform to the avian developmental pattern...
May 24, 2017: Journal of Experimental Zoology. Part B, Molecular and Developmental Evolution
https://www.readbyqxmd.com/read/28536862/mechanisms-of-hepatotoxicity-associated-with-the-monocyclic-%C3%AE-lactam-antibiotic-bal30072
#14
Franziska Paech, Simon Messner, Jochen Spickermann, Mathias Wind, Anne-Hortense Schmitt-Hoffmann, Anne Therese Witschi, Brett A Howell, Rachel J Church, Jeff Woodhead, Marc Engelhardt, Stephan Krähenbühl, Martina Maurer
BAL30072 is a new monocyclic β-lactam antibiotic under development which provides a therapeutic option for the treatment of severe infections caused by multi-drug-resistant Gram-negative bacteria. Despite the absence of liver toxicity in preclinical studies in rats and marmosets and in single dose clinical studies in humans, increased transaminase activities were observed in healthy subjects in multiple-dose clinical studies. We, therefore, initiated a comprehensive program to find out the mechanisms leading to hepatocellular injury using HepG2 cells (human hepatocellular carcinoma cell line), HepaRG cells (inducible hepatocytes derived from a human hepatic progenitor cell line), and human liver microtissue preparations...
May 23, 2017: Archives of Toxicology
https://www.readbyqxmd.com/read/28531964/non-electron-transfer-chain-mitochondrial-defects-differently-regulate-hif-1%C3%AE-degradation-and-transcription
#15
Antonina N Shvetsova, Daniela Mennerich, Juha M Kerätär, J Kalervo Hiltunen, Thomas Kietzmann
Mitochondria are the main consumers of molecular O2 in a cell as well as an abundant source of reactive oxygen species (ROS). Both, molecular oxygen and ROS are powerful regulators of the hypoxia-inducible factor-1α-subunit (HIF-α). While a number of mechanisms in the oxygen-dependent HIF-α regulation are quite well known, the view with respect to mitochondria is less clear. Several approaches using pharmacological or genetic tools targeting the mitochondrial electron transport chain (ETC) indicated that ROS, mainly formed at the Rieske cluster of complex III of the ETC, are drivers of HIF-1α activation...
August 2017: Redox Biology
https://www.readbyqxmd.com/read/28524096/itraq-mitoproteome-analysis-reveals-mechanisms-of-programmed-cell-death-in-arabidopsis-thaliana-induced-by-ochratoxin-a
#16
Yan Wang, Xiaoli Peng, Zhuojun Yang, Weiwei Zhao, Wentao Xu, Junran Hao, Weihong Wu, Xiao Li Shen, Yunbo Luo, Kunlun Huang
Ochratoxin A (OTA) is one of the most common and dangerous mycotoxins in the world. Previous work indicated that OTA could elicit spontaneous HR-like lesions formation Arabidopsis thaliana, reactive oxygen species (ROS) play an important role in OTA toxicity, and their major endogenous source is mitochondria. However, there has been no evidence as to whether OTA induces directly PCD in plants until now. In this study, the presence of OTA in Arabidopsisthaliana leaves triggered accelerated respiration, increased production of mitochondrial ROS, the opening of ROS-dependent mitochondrial permeability transition pores and a decrease in mitochondrial membrane potential as well as the release of cytochrome c into the cytosol...
May 18, 2017: Toxins
https://www.readbyqxmd.com/read/28522903/oxidative-stress-antioxidants-and-intestinal-calcium-absorption
#17
REVIEW
Gabriela Diaz de Barboza, Solange Guizzardi, Luciana Moine, Nori Tolosa de Talamoni
The disequilibrium between the production of reactive oxygen (ROS) and nitrogen (RNS) species and their elimination by protective mechanisms leads to oxidative stress. Mitochondria are the main source of ROS as by-products of electron transport chain. Most of the time the intestine responds adequately against the oxidative stress, but with aging or under conditions that exacerbate the ROS and/or RNS production, the defenses are not enough and contribute to developing intestinal pathologies. The endogenous antioxidant defense system in gut includes glutathione (GSH) and GSH-dependent enzymes as major components...
April 28, 2017: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/28511347/mitochondrial-complex-i-deactivation-is-related-to-superoxide-production-in-acute-hypoxia
#18
Pablo Hernansanz-Agustín, Elena Ramos, Elisa Navarro, Esther Parada, Nuria Sánchez-López, Laura Peláez-Aguado, J Daniel Cabrera-García, Daniel Tello, Izaskun Buendia, Anabel Marina, Javier Egea, Manuela G López, Anna Bogdanova, Antonio Martínez-Ruiz
Mitochondria use oxygen as the final acceptor of the respiratory chain, but its incomplete reduction can also produce reactive oxygen species (ROS), especially superoxide. Acute hypoxia produces a superoxide burst in different cell types, but the triggering mechanism is still unknown. Herein, we show that complex I is involved in this superoxide burst under acute hypoxia in endothelial cells. We have also studied the possible mechanisms by which complex I could be involved in this burst, discarding reverse electron transport in complex I and the implication of PTEN-induced putative kinase 1 (PINK1)...
August 2017: Redox Biology
https://www.readbyqxmd.com/read/28510056/the-two-sides-of-a-lipid-protein-story
#19
REVIEW
Luis G Mansor Basso, Luis F Santos Mendes, Antonio J Costa-Filho
Protein-membrane interactions play essential roles in a variety of cell functions such as signaling, membrane trafficking, and transport. Membrane-recruited cytosolic proteins that interact transiently and interfacially with lipid bilayers perform several of those functions. Experimental techniques capable of probing changes on the structural dynamics of this weak association are surprisingly limited. Among such techniques, electron spin resonance (ESR) has the enormous advantage of providing valuable local information from both membrane and protein perspectives by using intrinsic paramagnetic probes in metalloproteins or by attaching nitroxide spin labels to proteins and lipids...
June 2016: Biophysical Reviews
https://www.readbyqxmd.com/read/28509551/significance-of-2fe-2s-cluster-n1a-for-electron-transfer-and-assembly-of-escherichia-coli-respiratory-complex-i
#20
Katerina Dörner, Marta Vranas, Johannes Schimpf, Isabella R Straub, Jo Hoeser, Thorsten Friedrich
NADH:ubiquinone oxidoreductase, respiratory complex I, couples electron transfer from NADH to ubiquinone with proton translocation across the membrane. NADH reduces a noncovalently bound FMN, and the electrons are transported further to the quinone reduction site by a 95 Å long chain of seven iron-sulfur (Fe-S) clusters. Binuclear Fe-S cluster N1a is not part of this long chain but is located within electron transfer distance on the opposite site of FMN. The relevance of N1a to the mechanism of complex I is not known...
June 6, 2017: Biochemistry
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