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Mitochondrial diseases

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https://www.readbyqxmd.com/read/27921253/aberrant-alterations-of-mitochondrial-factors-drp1-and-opa1-in-the-brains-of-scrapie-experiment-rodents
#1
Xiao -Dong Yang, Qi Shi, Jing Sun, Yan Lv, Yue Ma, Cao Chen, Kang Xiao, Wei Zhou, Xiao-Ping Dong
The abnormal mitochondrial dynamics has been reported in the brains of some neurodegenerative diseases, such as Alzheimer's disease (AD) and Parkinson's disease (PD), but limitedly described in prion disease. Dynamin-related protein 1 (Drpl) and optic atrophy protein 1 (Opa1) are two essential elements for mitochondria fission and fusion. To evaluate possible changes of mitochondria dynamics during prion infection, the situations of brain Drp1 and Opa1 of scrapie strains 139A, ME7, and S15 mice, as well as 263K-infected hamsters, were analyzed...
December 6, 2016: Journal of Molecular Neuroscience: MN
https://www.readbyqxmd.com/read/27919931/low-mt-co1-in-monocytes-and-microvesicles-is-associated-with-outcome-in-patients-with-coronary-artery-disease
#2
Paul Holvoet, Maarten Vanhaverbeke, Katarzyna Bloch, Pieter Baatsen, Peter Sinnaeve, Stefan Janssens
BACKGROUND: Cytochrome oxidase (COX) IV complex regulates energy production in mitochondria. Impaired COX gene expression is related to obesity and type 2 diabetes mellitus, but whether it is directly related to the incidence of cardiovascular events is unknown. We investigated whether COX gene expression in monocytes is predictive for cardiovascular events in coronary artery disease patients. To avoid monocyte isolation from fresh blood, we then aimed to validate our findings in monocyte-derived microvesicles isolated from plasma...
December 5, 2016: Journal of the American Heart Association
https://www.readbyqxmd.com/read/27919073/mitochondrial-replacement-in-human-oocytes-carrying-pathogenic-mitochondrial-dna-mutations
#3
Eunju Kang, Jun Wu, Nuria Marti Gutierrez, Amy Koski, Rebecca Tippner-Hedges, Karen Agaronyan, Aida Platero-Luengo, Paloma Martinez-Redondo, Hong Ma, Yeonmi Lee, Tomonari Hayama, Crystal Van Dyken, Xinjian Wang, Shiyu Luo, Riffat Ahmed, Ying Li, Dongmei Ji, Refik Kayali, Cengiz Cinnioglu, Susan Olson, Jeffrey Jensen, David Battaglia, David Lee, Diana Wu, Taosheng Huang, Don P Wolf, Dmitry Temiakov, Juan Carlos Izpisua Belmonte, Paula Amato, Shoukhrat Mitalipov
Maternally inherited mitochondrial (mt)DNA mutations can cause fatal or severely debilitating syndromes in children, with disease severity dependent on the specific gene mutation and the ratio of mutant to wild-type mtDNA (heteroplasmy) in each cell and tissue. Pathogenic mtDNA mutations are relatively common, with an estimated 778 affected children born each year in the United States. Mitochondrial replacement therapies or techniques (MRT) circumventing mother-to-child mtDNA disease transmission involve replacement of oocyte maternal mtDNA...
November 30, 2016: Nature
https://www.readbyqxmd.com/read/27917618/prognostic-impact-of-mutt-homolog-1-expression-on-esophageal-squamous-cell-carcinoma
#4
Shingo Akiyama, Hiroshi Saeki, Yuichiro Nakashima, Makoto Iimori, Hiroyuki Kitao, Eiji Oki, Yoshinao Oda, Yusaku Nakabeppu, Yoshihiro Kakeji, Yoshihiko Maehara
MutT homolog-1 (MTH1) is a pyrophosphatase that acts on oxidized nucleotides and hydrolyzes 8-oxo-2'-deoxyguanosine triphosphate in deoxynucleoside triphosphate pool to prevent its incorporation into nuclear and mitochondrial DNA, result in reduce cytotoxicity in tumor cells. MTH1 is overexpressed in various cancers and is considered as a therapeutic target. Environmental factors such as cigarette smoking and alcohol consumption are critical risk factors for the development and progression of esophageal squamous cell carcinoma (ESCC), suggesting that oxidative stress contributes to the pathogenesis of ESCC...
December 5, 2016: Cancer Medicine
https://www.readbyqxmd.com/read/27917591/the-pde4-inhibitor-roflumilast-reduces-weight-gain-by-increasing-energy-expenditure-and-leads-to-improved-glucose-metabolism
#5
Julia Möllmann, Florian Kahles, Corinna Lebherz, Ben Kappel, Christer Baeck, Frank Tacke, Christian Werner, Massimo Federici, Nikolaus Marx, Michael Lehrke
AIMS: The PDE4 inhibitor roflumilast is a clinically approved anti-inflammatory drug used for the treatment of chronic obstructive pulmonary disease. In addition, roflumilast was found to reduce body weight and improve glucose metabolism by a yet unknown mechanism. MATERIALS AND METHODS: Metabolic effects of roflumilast were investigated in C57BL/6J mice on high fat western-type diet treated with or without roflumilast for a period of 12 weeks. RESULTS: Roflumilast led to a marked reduction of body weight gain, which became apparent in the second week following treatment initiation and was attributable to a pronounced increase of energy expenditure...
December 5, 2016: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/27917156/inhibitory-effects-of-macrotetrolides-from-streptomyces-spp-on-zoosporogenesis-and-motility-of-peronosporomycete-zoospores-are-likely-linked-with-enhanced-atpase-activity-in-mitochondria
#6
Md Tofazzal Islam, Hartmut Laatsch, Andreas von Tiedemann
The release of zoospores from sporangia and motility of the released zoospores are critical in the disease cycle of the Peronosporomycetes that cause devastating diseases in plants, fishes, animals and humans. Disruption of any of these asexual life stages eliminates the possibility of pathogenesis. In the course of screening novel bioactive secondary metabolites, we found that extracts of some strains of marine Streptomyces spp. rapidly impaired motility and caused subsequent lysis of zoospores of the grapevine downy mildew pathogen Plasmopara viticola at 10 μg/ml...
2016: Frontiers in Microbiology
https://www.readbyqxmd.com/read/27917122/glucagon-like-peptide-1-analog-liraglutide-delays-onset-of-experimental-autoimmune-encephalitis-in-lewis-rats
#7
Brian DellaValle, Gitte S Brix, Birgitte Brock, Michael Gejl, Anne M Landau, Arne Møller, Jørgen Rungby, Agnete Larsen
Introduction: Recent findings indicate that metabolic disturbances are involved in multiple sclerosis (MS) pathology and influence the susceptibility to treatment, directing attention toward anti-diabetic drugs such as metformin and pioglitazone. Liraglutide, a drug of the glucagon-like peptide-1 (GLP-1) family, is also anti-diabetic and weight-reducing and is, moreover, directly neuroprotective and anti-inflammatory in a broad spectrum of experimental models of brain disease. In this study we investigate the potential for this FDA-approved drug, liraglutide, as a treatment for MS by utilizing the experimental model, experimental autoimmune encephalitis (EAE)...
2016: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/27916896/the-impact-of-cxcr4-blockade-on-the-survival-of-rat-brain-cortical-neurons
#8
José Joaquín Merino, Alba Garcimartín, María Elvira López-Oliva, Juana Benedí, María Pilar González
BACKGROUND: Chemokine receptor type 4 (CXCR4) plays a role in neuronal survival/cell repair and also contributes to the progression of cancer and neurodegenerative diseases. Chemokine ligand 12 (CXCL12) binds to CXCR4. In this study, we have investigated whether CXCR4 blockade by AMD3100 (a CXCR4 antagonist, member of bicyclam family) may affect neuronal survival in the absence of insult. Thus, we have measured the mitochondrial membrane potential (MMP), Bax and Bcl-2 protein translocation, and cytochrome c release in AMD3100-treated brain cortical neurons at 7 DIV (days in vitro)...
November 30, 2016: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/27916650/cardiac-oxidative-stress-in-diabetes-mechanisms-and-therapeutic-potential
#9
REVIEW
Alyssa Faria, Shanta J Persaud
Macrovascular complications of diabetes, including diabetic cardiovascular disease (CVD), occur through a number of hyperglycaemia-induced mechanisms that include generation of oxidative stress, accumulation of advanced glycation end-products (AGE) and activation of protein kinase C (PKC). Cardiac oxidative stress is associated with increased cardiac fibrosis and hypertrophy, and reduced cardiac performance and contractility, leading to severe cardiac dysfunction and potentially fatal cardiac events. It occurs under conditions of excessive synthesis of reactive oxygen species (ROS)...
December 1, 2016: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/27916644/targeted-mitochondrial-uncoupling-beyond-ucp1-the-fine-line-between-death-and-metabolic-health
#10
REVIEW
Mario Ost, Susanne Keipert, Susanne Klaus
In the early 1930s, the chemical uncoupling agent 2,4-dinitrophenol (DNP) was promoted for the very first time as a powerful and effective weight loss pill but quickly withdrawn from the market due to its lack of tissue-selectivity with resulting dangerous side effects, including hyperthermia and death. Today, novel mitochondria- or tissue-targeted chemical uncouplers with higher safety and therapeutic values are under investigation in order to tackle obesity, diabetes and fatty liver disease. Moreover, in the past 20 years, transgenic mouse models were generated to understand the molecular and metabolic consequences of targeted uncoupling, expressing functional uncoupling protein 1 (UCP1) ectopically in white adipose tissue or skeletal muscle...
December 1, 2016: Biochimie
https://www.readbyqxmd.com/read/27916526/the-mitochondrial-lon-protease-is-required-for-age-specific-and-sex-specific-adaptation-to-oxidative-stress
#11
Laura C D Pomatto, Caroline Carney, Brenda Shen, Sarah Wong, Kelly Halaszynski, Matthew P Salomon, Kelvin J A Davies, John Tower
Multiple human diseases involving chronic oxidative stress show a significant sex bias, including neurodegenerative diseases, cancer, immune dysfunction, diabetes, and cardiovascular disease. However, a possible molecular mechanism for the sex bias in physiological adaptation to oxidative stress remains unclear. Here, we report that Drosophila melanogaster females but not males adapt to hydrogen peroxide stress, whereas males but not females adapt to paraquat (superoxide) stress. Stress adaptation in each sex requires the conserved mitochondrial Lon protease and is associated with sex-specific expression of Lon protein isoforms and proteolytic activity...
November 23, 2016: Current Biology: CB
https://www.readbyqxmd.com/read/27916511/liqustri-lucidi-fructus-inhibits-hepatic-injury-and-functions-as-an-antioxidant-by-activation-of-amp-activated-protein-kinase-in-vivo-and-in-vitro
#12
Hye Lim Seo, Su Youn Baek, Eun Hye Lee, Ju-Hee Lee, Seul-Gi Lee, Kwang-Youn Kim, Mi Hee Jang, Min-Hui Park, Joung-Hee Kim, Keun-Jun Kim, Hyeong Sik Lee, Soon-Cheol Ahn, Jong Rok Lee, Sook Jahr Park, Sang Chan Kim, Young Woo Kim
Medicinal herbs are used to treat or prevent various diseases, and function to regulate protective mechanisms as nutraceuticals. Fructus Ligustri lucidi is the fruit of Ligustrum lucidum and has been used for its tonic effects on the liver. This study was designed to examine the effects of Fructus Ligustri lucidi water extract (FLL) against severe oxidative stress and mitochondrial impairment in vivo and in vitro and to elucidate its cellular mechanisms of action. Treatment of HepG2 cells with arachidonic acid (AA) + iron successfully induced oxidative stress and apoptosis, as indicated by depletion of glutathione, formation of ROS, increases in mitochondrial membrane permeability (MMP), and altered expression of apoptosis-related proteins, such as procaspase-3 and Bcl-xL...
December 1, 2016: Chemico-biological Interactions
https://www.readbyqxmd.com/read/27915046/dna-damage-related-crosstalk-between-the-nucleus-and-mitochondria
#13
Mohammad Saki, Aishwarya Prakash
The electron transport chain is the primary pathway by which a cell generates energy in the form of ATP. Byproducts of this process produce reactive oxygen species that can cause damage to mitochondrial DNA. If not properly repaired, the accumulation of DNA damage can lead to mitochondrial dysfunction linked to several human disorders including neurodegenerative diseases and cancer. Mitochondria are able to combat oxidative DNA damage via repair mechanisms that are analogous to those found in the nucleus. Of the repair pathways currently reported in the mitochondria, the base excision repair pathway is the most comprehensively described...
November 30, 2016: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/27914997/transcriptomic-profiles-of-striped-snakehead-fish-cells-ssn-1-infected-with-red-spotted-grouper-nervous-necrosis-virus-rgnnv-with-an-emphasis-on-apoptosis-pathway
#14
Wenjie Chen, Lizhu Yi, Shuangshuang Feng, Xiaodan Liu, Muhammad Asim, Yongcan Zhou, Jiangfeng Lan, Sanjie Jiang, Jiagang Tu, Li Lin
Nervous necrosis virus (NNV), the causative agent of viral nervous necrosis (VNN) disease, has caused mass mortality of cultured marine and freshwater fish worldwide, resulting in enormous economic losses in the aquaculture industry. However, the molecular mechanisms underlying the pathogenicity of NNV are still poorly understood. In this study, the transcriptomic profiles of striped snakehead fish (Channa striatus) cells (SSN-1) infected with red-spotted grouper NNV (RGNNV) were investigated using deep RNA sequencing technique...
November 30, 2016: Fish & Shellfish Immunology
https://www.readbyqxmd.com/read/27914941/therapeutic-role-of-sirtuins-in-neurodegenerative-disease-and-their-modulation-by-polyphenols
#15
REVIEW
Marjan Ajami, Hamidreza Pazoki-Toroudi, Hamed Amani, Seyed Fazel Nabavi, Nady Braidy, Rosa Anna Vacca, Atanas Georgiev Atanasov, Andrei Mocan, Seyed Mohammad Nabavi
Searching for effective therapeutic agents‏‎ to ‎‏prevent‏ ‏neurodegeneration ‎is a challenging task due ‎to ‎the growing list of neurodegenerative disorders associated with a multitude of inter-related pathways.‎ The induction and inhibition of several different signaling pathways has been shown to slow down and/or attenuate ‎neurodegeneration and decline in cognition and locomotor function. Among these signaling pathways, a new class of enzymes known as sirtuins or silent information regulators of gene transcription has been shown to play important regulatory roles in the ageing process...
November 30, 2016: Neuroscience and Biobehavioral Reviews
https://www.readbyqxmd.com/read/27914013/inhibitory-effect-of-homocysteine-on-rat-neural-stem-cell-growth-in-vitro-is-associated-with-reduced-protein-levels-and-enzymatic-activities-of-aconitase-and-respiratory-complex-iii
#16
Xu-Mei Zhang, Ya-Qian Zhao, Hai Yan, Huan Liu, Guo-Wei Huang
Increased blood plasma concentration of the sulphur amino acid homocysteine (Hcy) is considered as an independent risk factor of the neurodegenerative diseases. However, the detailed molecular mechanisms by which Hcy leads to neurotoxicity have yet to be clarified. Recent research has suggested that neurotoxicity of Hcy may involve negative regulation of neural stem cell (NSC) proliferation. In the current study, primary NSCs were isolated from neonatal rat brain hippocampus and the inhibition in cell growth was observed after exposure to l50 μM and 500 μM L-Hcy...
December 2, 2016: Journal of Bioenergetics and Biomembranes
https://www.readbyqxmd.com/read/27913844/global-dna-methylation-profiling-of-manganese-exposed-human-neuroblastoma-sh-sy5y-cells-reveals-epigenetic-alterations-in-parkinson-s-disease-associated-genes
#17
Prashant Tarale, Saravanadevi Sivanesan, Atul P Daiwile, Reinhard Stöger, Amit Bafana, Pravin K Naoghare, Devendra Parmar, Tapan Chakrabarti, Krishnamurthi Kannan
Manganese (Mn) is an essential trace element required for optimal functioning of cellular biochemical pathways in the central nervous system. Elevated exposure to Mn through environmental and occupational exposure can cause neurotoxic effects resulting in manganism, a condition with clinical symptoms identical to idiopathic Parkinson's disease. Epigenetics is now recognized as a biological mechanism involved in the etiology of various diseases. Here, we investigated the role of DNA methylation alterations induced by chronic Mn (100 µM) exposure in human neuroblastoma (SH-SY5Y) cells in relevance to Parkinson's disease...
December 2, 2016: Archives of Toxicology
https://www.readbyqxmd.com/read/27913766/myocardial-cytochrome-oxidase-activity-increases-with-age-and-hypoxemia-in-patients-with-congenital-heart-disease
#18
Michael Onwugbufor, Richard J Levy, David Zurakowski, Richard A Jonas, Pranava Sinha
BACKGROUND: Myocardial tolerance to ischemia is influenced by age and preoperative cyanosis through unknown mechanisms and significantly affects postoperative outcomes. Cytochrome c oxidase (CcOx), the terminal enzyme of the mitochondrial electron transport chain, may play a role in the susceptibility to ischemic-reperfusion (IR) injury. Our study aimed at investigating changes in human myocardial CcOx activity based on age and preoperative oxygen saturation to understand its role in transition from neonatal to mature myocardium and hypoxic conditions...
December 1, 2016: Perfusion
https://www.readbyqxmd.com/read/27913697/is-mitochondrial-oxidative-metabolism-the-right-therapy-target-in-early-huntington-disease
#19
Raffaele Lodi
No abstract text is available yet for this article.
December 2, 2016: Neurology
https://www.readbyqxmd.com/read/27913620/pb1-f2-derived-from-avian-influenza-a-virus-h7n9-induces-inflammation-via-activation-of-the-nlrp3-inflammasome
#20
Anita Pinar, Jennifer K Dowling, Natalie J Bitto, Avril B Robertson, Eicke Latz, Cameron R Stewart, Grant R Drummond, Matthew A Cooper, Julie L McAuley, Michelle D Tate, Ashley Mansell
The emergence of avian H7N9 influenza A virus (IAV) in humans with associated high mortality, has highlighted the threat of a potential pandemic. Fatal H7N9 infections are characterised by hyperinflammation and increased cellular infiltrates in the lung. Currently there are limited therapies to address the pathologies associated with H7N9 infection and what virulence factors may contribute to these pathologies. We have found that PB1-F2 derived from H7N9 activates the NLRP3 inflammasome and induces lung inflammation and cellular recruitment that is NLRP3 dependent...
December 2, 2016: Journal of Biological Chemistry
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