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https://www.readbyqxmd.com/read/28927263/molecular-and-cellular-basis-of-neurodegeneration-in-alzheimer-s-disease
#1
Sangyun Jeong
The most common form of senile dementia is Alzheimer's disease (AD), which is characterized by the extracellular deposition of amyloid beta-peptide (Abeta) plaques and the intracellular formation of neurofibrillary tangles (NFTs) in the cerebral cortex. Tau abnormalities are commonly observed in many neurodegenerative diseases including AD, Parkinson's disease, and Pick's disease. Interestingly, tau-mediated formation of NFTs in AD brains shows better correlation with cognitive impairment than Abeta plaque accumulation; pathological tau alone is sufficient to elicit frontotemporal dementia, but it does not cause AD...
September 20, 2017: Molecules and Cells
https://www.readbyqxmd.com/read/28926603/scavenging-of-reactive-oxygen-species-by-astaxanthin-inhibits-epithelial-mesenchymal-transition-in-high-glucose-stimulated-mesothelial-cells
#2
Kazuaki Hara, Chieko Hamada, Keiichi Wakabayashi, Reo Kanda, Kayo Kaneko, Satoshi Horikoshi, Yasuhiko Tomino, Yusuke Suzuki
BACKGROUND: High glucose concentrations influence the functional and structural development of the peritoneal membrane. We previously reported that the oral administration of astaxanthin (AST) suppressed peritoneal fibrosis (PF) as well as inhibited oxidative stress, inflammation, and epithelial-mesenchymal transition (EMT) of peritoneal mesothelial cells (PMCs) in a chlorhexidine-induced PF rat model. This suggests that oxidative stress induction of EMT is a key event during peritoneal damage...
2017: PloS One
https://www.readbyqxmd.com/read/28925723/expression-patterns-of-members-of-the-isocitrate-dehydrogenase-gene-family-in-murine-inner-ear
#3
Y-R Kim, K-H Kim, S Lee, S-K Oh, J-W Park, K-Y Lee, J-I Baek, U-K Kim
Age-related hearing loss (ARHL) is characterized by an age-dependent decline of auditory function characterized by with loss of sensory hair cells, spiral ganglion neurons, and stria vascularis (SV) cells in the cochlea of the inner ear. Aging and age-related diseases result from accumulated oxidative damage caused by reactive oxygen species (ROS) generated by mitochondria. The isocitrate dehydrogenase (IDH) family includes three enzymes in human cells: IDH1, IDH2, and IDH3. Although all three enzymes catalyze the same enzymatic reaction, that is, oxidative decarboxylation of isocitrate to produce α-ketoglutarate, each IDH enzyme has unique features...
September 19, 2017: Biotechnic & Histochemistry: Official Publication of the Biological Stain Commission
https://www.readbyqxmd.com/read/28925688/live-cell-imaging-of-mitochondrial-autophagy-with-a-novel-fluorescent-small-molecule
#4
Hidefumi Iwashita, Satoru Torii, Noriyoshi Nagahora, Munetaka Ishiyama, Kosei Shioji, Kazumi Sasamoto, Shigeomi Shimizu, Kentaro Okuma
There has been a growing interest in mitophagy, mitochondria-selective autophagy, which plays an essential role in maintaining intracellular homeostasis. We have developed a small-molecule fluorescent probe, Mtphagy Dye, for visualizing mitophagy, which was readily synthesized from a known perylene derivative, perylene-3,4-dicarboxylic anhydride. Mtphagy Dye has suitable fluorescent properties for detecting mitochondrial acidification during mitophagy at the long-wavelength region that does not damage mitochondria...
September 19, 2017: ACS Chemical Biology
https://www.readbyqxmd.com/read/28922472/mirna-506-promotes-primary-biliary-cholangitis-like-features-in-cholangiocytes-and-immune-activation
#5
Oihane Erice, Patricia Munoz-Garrido, Javier Vaquero, Maria J Perugorria, Maite G Fernandez-Barrena, Elena Saez, Alvaro Santos-Laso, Ander Arbelaiz, Raul Jimenez-Agüero, Joaquin Fernandez-Irigoyen, Enrique Santamaria, Verónica Torrano, Arkaitz Carracedo, Meenakshisundaram Ananthanarayanan, Marco Marzioni, Jesus Prieto, Ulrich Beuers, Ronald P Oude Elferink, Nicholas F LaRusso, Luis Bujanda, Jose J G Marin, Jesus M Banales
Primary biliary cholangitis (PBC) is a chronic cholestatic liver disease associated with autoimmune phenomena targeting intrahepatic bile duct cells (cholangiocytes). Although PBC etiopathogenesis still remains obscure, development of anti-mitochondrial auto-antibodies against pyruvate dehydrogenase complex-E2 (PDC-E2) is a common feature. MicroRNA (miR) dysregulation occurs in liver and immune cells of PBC patients, but their functional relevance is largely unknown. We previously reported that miR-506 is overexpressed in PBC cholangiocytes and directly targets both Cl(-) /HCO3(-) anion exchanger 2 (AE2) and type III inositol 1,4,5-trisphosphate receptor (InsP3R3), leading to cholestasis...
September 18, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/28922345/tilianin-post-conditioning-attenuates-myocardial-ischemia-reperfusion-injury-via-mitochondrial-protection-and-inhibition-of-apoptosis
#6
Yangyang Wang, Yong Yuan, Xinchun Wang, Yanfang Wang, Jiang Cheng, Li Tian, Xinhong Guo, Dongmei Qin, Wenjiang Cao
BACKGROUND The aim of this study was to investigate the role of tilianin in modulating mitochondrial functions and mitochondria-mediated apoptosis during cardio-protection. MATERIAL AND METHODS Myocardial ischemia/reperfusion (I/R) injury was induced by 30 minutes coronary occlusion followed by two hours reperfusion in Sprague-Dawley rats. To investigate the cardio-protective effects of tilianin, apoptosis was evaluated by TUNEL. Mitochondrial ultrastructure and function were assessed by transmission electron microscopy, dynamics of mitochondrial permeability transition pore (mPTP) opening and ATP production in the myocardium; Ca2+ content and reactive oxygen species (ROS) were measured to evaluated the level of damage factors in the mitochondria...
September 18, 2017: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
https://www.readbyqxmd.com/read/28919754/preparation-of-coffee-oil-algae-oil-based-nanoemulsions-and-the-study-of-their-inhibition-effect-on-uva-induced-skin-damage-in-mice-and-melanoma-cell-growth
#7
Chu-Ching Yang, Chi-Feng Hung, Bing-Huei Chen
Coffee grounds, a waste by-product generated after making coffee, contains approximately 15% coffee oil which can be used as a raw material in cosmetics. Algae oil rich in docosahexaenoic acid (DHA) has been demonstrated to possess anticancer and anti-inflammation functions. The objectives of this study were to develop a gas chromatography-mass spectrometry (GC-MS) method for the determination of fatty acids in coffee oil and algae oil and prepare a nanoemulsion for studying its inhibition effect on ultraviolet A-induced skin damage in mice and growth of melanoma cells B16-F10...
2017: International Journal of Nanomedicine
https://www.readbyqxmd.com/read/28919358/perfused-human-hepatocyte-microtissues-identify-reactive-metabolite-forming-and-mitochondria-perturbing-hepatotoxins
#8
Cliff Rowe, Mohsen Shaeri, Emma Large, Terri Cornforth, Angela Robinson, Tomasz Kostrzewski, Rowena Sison-Young, Christopher Goldring, Kevin Park, David Hughes
Hepatotoxins cause liver damage via many mechanisms but the formation of reactive metabolites and/or damage to liver mitochondria are commonly implicated. We assess 3D human primary hepatocyte microtissues as a platform for hepatotoxicity studies with reactive metabolite-forming and mitochondria-perturbing compounds. We show that microtissues formed from cryopreserved human hepatocytes had bile canaliculi, transcribed mRNA from genes associated with xenobiotic metabolism and expressed functional cytochrome P450 enzymes...
September 15, 2017: Toxicology in Vitro: An International Journal Published in Association with BIBRA
https://www.readbyqxmd.com/read/28918334/inner-mechanism-of-protection-of-mitochondrial-electron-transfer-proteins-against-oxidative-damage-focus-on-hydrogen-peroxide-decomposition
#9
Erik Sedlak, Andrej Musatov
It is generally recognized that the mitochondria are the major source of reactive oxygen species including hydrogen peroxide (H2O2). Although the local concentration of H2O2 near the electron-transfer chain is potentially quite high, the chain's components are rarely found to be significantly damaged by H2O2. Our experimental data, as well as the data published by others, suggest that mitochondrial electron-transfer proteins, which are in the first line to be harmed by ROS, are well prepared to defend themselves...
September 13, 2017: Biochimie
https://www.readbyqxmd.com/read/28917665/improving-mitochondrial-function-significantly-reduces-metabolic-visual-motor-and-cognitive-decline-in-aged-drosophila-melanogaster
#10
Tobias W Weinrich, Ariathney Coyne, Thomas E Salt, Christopher Hogg, Glen Jeffery
Mitochondria play a major role in aging. Over time, mutations accumulate in mitochondrial DNA leading to reduced adenosine triphosphate (ATP) production and increased production of damaging reactive oxygen species. If cells fail to cope, they die. Reduced ATP will result in declining cellular membrane potentials leading to reduced central nervous system function. However, aged mitochondrial function is improved by long wavelength light (670 nm) absorbed by cytochrome c oxidase in mitochondrial respiration...
August 30, 2017: Neurobiology of Aging
https://www.readbyqxmd.com/read/28916822/ampk-phosphorylation-of-ulk1-is-required-for-targeting-of-mitochondria-to-lysosomes-in-exercise-induced-mitophagy
#11
Rhianna C Laker, Joshua C Drake, Rebecca J Wilson, Vitor A Lira, Bevan M Lewellen, Karen A Ryall, Carleigh C Fisher, Mei Zhang, Jeffrey J Saucerman, Laurie J Goodyear, Mondira Kundu, Zhen Yan
Mitochondrial health is critical for skeletal muscle function and is improved by exercise training through both mitochondrial biogenesis and removal of damaged/dysfunctional mitochondria via mitophagy. The mechanisms underlying exercise-induced mitophagy have not been fully elucidated. Here, we show that acute treadmill running in mice causes mitochondrial oxidative stress at 3-12 h and mitophagy at 6 h post-exercise in skeletal muscle. These changes were monitored using a novel fluorescent reporter gene, pMitoTimer, that allows assessment of mitochondrial oxidative stress and mitophagy in vivo, and were preceded by increased phosphorylation of AMP activated protein kinase (Ampk) at tyrosine 172 and of unc-51 like autophagy activating kinase 1 (Ulk1) at serine 555...
September 15, 2017: Nature Communications
https://www.readbyqxmd.com/read/28915507/ambient-fine-particulate-matters-induce-cell-death-and-inflammatory-response-by-influencing-mitochondria-function-in-human-corneal-epithelial-cells
#12
Eun-Jung Park, Jae-Byoung Chae, Jungmook Lyu, Cheolho Yoon, Sanghwa Kim, Changjoo Yeom, Younghun Kim, Jaerak Chang
Ambient fine particulate matter (AFP) is a main risk factor for the cornea as ultraviolet light. However, the mechanism of corneal damage following exposure to AFP has been poorly understood. In this study, we first confirmed that AFP can penetrate the cornea of mice, considering that two-dimensional cell culture systems are limited in reflecting the situation in vivo. Then, we investigated the toxic mechanism using human corneal epithelial (HCET) cells. At 24h after exposure, AFP located within the autophagosome-like vacuoles, and cell proliferation was clearly inhibited in all the tested concentration...
September 12, 2017: Environmental Research
https://www.readbyqxmd.com/read/28915214/non-hemodynamic-effects-of-catecholamines
#13
Clair Hartmann, Peter Radermacher, Martin Wepler, Benedikt Nußbaum
Circulatory shock is defined as an imbalance between tissue oxygen supply and demand, and mostly results from a loss of blood volume, cardiac pump failure, and/or reduction of vasomotor tone. The clinical hallmarks of circulatory shock are arterial hypotension and lactate acidosis. Since the degree and duration of hypotension are major determinants of outcome, vasopressor administration represents a cornerstone therapy to treat these patients. Current guidelines recommend the use of catecholamines as the drug of first choice...
October 2017: Shock
https://www.readbyqxmd.com/read/28914755/thioredoxin-2-offers-protection-against-mitochondrial-oxidative-stress-in-h9c2-cells-and-against-myocardial-hypertrophy-induced-by-hyperglycemia
#14
Hong Li, Changqing Xu, Quanfeng Li, Xiuxiang Gao, Erkio Sugano, Hiroshi Tomita, Liming Yang, Sa Shi
Mitochondrial oxidative stress is thought to be a key contributor towards the development of diabetic cardiomyopathy. Thioredoxin 2 (Trx2) is a mitochondrial antioxidant that, along with Trx reductase 2 (TrxR2) and peroxiredoxin 3 (Prx3), scavenges H₂O₂ and offers protection against oxidative stress. Our previous study showed that TrxR inhibitors resulted in Trx2 oxidation and increased ROS emission from mitochondria. In the present study, we observed that TrxR inhibition also impaired the contractile function of isolated heart...
September 15, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28914132/reverse-electron-transfer-results-in-a-loss-of-flavin-from-mitochondrial-complex-i-potential-mechanism-for-brain-ischemia-reperfusion-injury
#15
Anna Stepanova, Anja Kahl, Csaba Konrad, Vadim Ten, Anatoly S Starkov, Alexander Galkin
Ischemic stroke is one of the most prevalent sources of disability in the world. The major brain tissue damage takes place upon the reperfusion of ischemic tissue. Energy failure due to alterations in mitochondrial metabolism and elevated production of reactive oxygen species (ROS) is one of the main causes of brain ischemia-reperfusion (IR) damage. Ischemia resulted in the accumulation of succinate in tissues, which favors the process of reverse electron transfer (RET) when a fraction of electrons derived from succinate is directed to mitochondrial complex I for the reduction of matrix NAD(+)...
January 1, 2017: Journal of Cerebral Blood Flow and Metabolism
https://www.readbyqxmd.com/read/28912677/reversible-axonal-dystrophy-by-calcium-modulation-in-frataxin-deficient-sensory-neurons-of-yg8r-mice
#16
Belén Mollá, Diana C Muñoz-Lasso, Fátima Riveiro, Arantxa Bolinches-Amorós, Federico V Pallardó, Angel Fernandez-Vilata, María de la Iglesia-Vaya, Francesc Palau, Pilar Gonzalez-Cabo
Friedreich's ataxia (FRDA) is a peripheral neuropathy involving a loss of proprioceptive sensory neurons. Studies of biopsies from patients suggest that axonal dysfunction precedes the death of proprioceptive neurons in a dying-back process. We observed that the deficiency of frataxin in sensory neurons of dorsal root ganglia (DRG) of the YG8R mouse model causes the formation of axonal spheroids which retain dysfunctional mitochondria, shows alterations in the cytoskeleton and it produces impairment of axonal transport and autophagic flux...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28905953/protective-effect-of-potentilla-anserina-polysaccharide-on-cadmium-induced-nephrotoxicity-in-vitro-and-in-vivo
#17
Rong Shen, Disheng Liu, Chenchen Hou, Di Liu, Lixia Zhao, Ju Cheng, Degui Wang, Decheng Bai
The aim of this research was to investigate the antioxidant and anti-apoptotic activities of Potentilla anserina polysaccharide (PAP) on kidney damage induced by cadmium (Cd) in vitro and in vivo. PAP has been suggested to have anti-oxidation, anti-apoptosis, immunoregulation, antimicrobial, antitussive, and expectorant abilities. In this study, PAP was extracted and the major components of PAP were analyzed. It was shown that PAP pretreatment remarkably improved redox homeostasis, both in human embryonic kidney 293 (HEK293) cells and in BALB/c mice...
September 14, 2017: Food & Function
https://www.readbyqxmd.com/read/28904321/altered-expression-of-mitochondrial-antioxidants-in-oral-squamous-cell-carcinoma
#18
Sumita Banerjee, Saikat Mukherjee, Sanjib Mitra, Pallav Singhal
Reactive oxygen species, if produced in excess by oxidative phosphorylation, contributes to mitochondrial DNA damage and progressive respiratory chain dysfunction, leading to various diseases including carcinogenesis. Mitochondria are susceptible to oxidative stress (OS) owing to lack of introns, protective histones, and DNA repair enzymes. However, mitochondria are protected from OS by numerous antioxidants such as superoxide dismutase 2 (SOD2), catalase, glutaredoxin 2 (GLRX2), reduced glutathione (GSH), glutathione peroxidase (GPX), and thioredoxin 2 (TXN2)...
2017: Journal of Oral Science
https://www.readbyqxmd.com/read/28904018/dyslipidemia-impairs-mitochondrial-trafficking-and-function-in-sensory-neurons
#19
Amy E Rumora, Stephen I Lentz, Lucy M Hinder, Samuel W Jackson, Andrew Valesano, Gideon E Levinson, Eva L Feldman
Mitochondrial trafficking plays a central role in dorsal root ganglion (DRG) neuronal cell survival and neurotransmission by transporting mitochondria from the neuronal cell body throughout the bundles of DRG axons. In type 2 diabetes (T2DM), dyslipidemia and hyperglycemia damage DRG neurons and induce mitochondrial dysfunction; however, the impact of free fatty acids and glucose on mitochondrial trafficking in DRG neurons remains unknown. To evaluate the impact of free fatty acids compared to hyperglycemia on mitochondrial transport, primary adult mouse DRG neuron cultures were treated with physiologic concentrations of palmitate and glucose and assessed for alterations in mitochondrial trafficking, mitochondrial membrane potential, and mitochondrial bioenergetics...
September 13, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28903499/the-long-lasting-rodenticide-brodifacoum-induces-neuropathology-in-adult-male-rats
#20
Sergey Kalinin, Natalia Marangoni, Katarzyna Kowal, Arunangsu Dey, Kinga Lis, Sergey Brodsky, Richard van Breemen, Zane Hauck, Richard Ripper, Israel Rubinstein, Guy Weinberg, Douglas L Feinstein
Superwarfarins are very long-lasting rodenticides effective in warfarin-resistant rodents at extremely low doses. The consequences of chronic superwarfarin levels in tissues, due to biological half-lives on the order of 20 days, have not been examined. We now characterized the neurological effects of brodifacoum (BDF), one of the most widely used superwarfarins, in adult male Sprague Dawley rats. Dosing curves established the acute oral lethal dose for BDF as 221 ± 14 μg/kg. Measurement of tissue BDF levels showed accumulation throughout the body, including the central nervous system, with levels diminishing over several days...
September 1, 2017: Toxicological Sciences: An Official Journal of the Society of Toxicology
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