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https://www.readbyqxmd.com/read/28209717/autophagy-metabolism-and-cancer
#1
Jessie Yanxiang Guo, Eileen White
Macroautophagy (autophagy hereafter) is a process that collects cytoplasmic components, particularly mitochondria, and degrades them in lysosomes. In mammalian systems, basal autophagy levels are normally low but are profoundly stimulated by starvation and essential for survival. Cancer cells up-regulate autophagy and can be more autophagy-dependent than most normal tissues. Genetic deficiency in essential autophagy genes in tumors in many autochthonous mouse models for cancer reduces tumor growth. In K-ras(G12D)-driven non-small cell lung cancer (NSCLC) and other models, autophagy sustains metabolism and survival...
February 16, 2017: Cold Spring Harbor Symposia on Quantitative Biology
https://www.readbyqxmd.com/read/28195448/mitochondrion-anchoring-photosensitizer-with-aggregation-induced-emission-characteristics-synergistically-boosts-the-radiosensitivity-of-cancer-cells-to-ionizing-radiation
#2
Chris Y Y Yu, Huae Xu, Shenglu Ji, Ryan T K Kwok, Jacky W Y Lam, Xiaolin Li, Sunil Krishnan, Dan Ding, Ben Zhong Tang
The first mitochondrion-anchoring photosensitizer that specifically generates singlet oxygen ((1) O2 ) in mitochondria under white light irradiation that can serve as a highly effective radiosensitizer is reported here, significantly sensitizing cancer cells to ionizing radiation. An aggregation-induced emission luminogen (AIEgen), namely DPA-SCP, is rationally designed with α-cyanostilbene as a simple building block to reveal AIE, diphenylamino (DPA) group as a strong electron donating group to benefit red emission and efficient light-controlled (1) O2 generation, as well as a pyridinium salt as the targeting moiety to ensure specific mitochondrial localization...
February 13, 2017: Advanced Materials
https://www.readbyqxmd.com/read/28170536/astrocytes-in-the-optic-nerve-head-of-glaucomatous-mice-display-a-characteristic-reactive-phenotype
#3
Rui Wang, Philip Seifert, Tatjana C Jakobs
Purpose: Optic nerve head astrocytes, a subtype of white-matter astrocytes, become reactive early in the course of glaucoma. It was shown recently that in the DBA/2J mouse model of inherited glaucoma optic nerve astrocytes extend new longitudinal processes into the axon bundles before ganglion cell loss becomes apparent. The present study aims at testing whether this behavior of astrocytes is typical of early glaucomatous damage. Methods: Mice expressing green fluorescent protein in individual astrocytes were used to evaluate the early response of astrocytes in the glial lamina of the optic nerve head after increasing the IOP using the microbead occlusion method...
February 1, 2017: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/28123139/remodeling-of-rat-stromal-vascular-cells-to-brite-beige-adipocytes-by-prolyl-hydroxyproline
#4
Jun A Minaguchi, Sakino Ogata, Naoki Takahashi, Takuya Hirose, Hiromi Ueda, Kazushige Takehana
The aim of this study was to determine the effects of prolyl-hydroxyproline (Pro-Hyp) on the proliferation and differentiation of rat stromal-vascular cells (SVCs) being cultured in a medium with (Pro-Hyp group) or without Pro-Hyp (control group). The results showed that there was no significant difference in proliferation rate of SVCs, lipid droplet (LD) diameter or intracellular concentration of triglycerides between two groups. However, the diameter range of LDs in the Pro-Hyp group tended to be smaller than that in the control group...
January 26, 2017: Journal of Veterinary Medical Science
https://www.readbyqxmd.com/read/28102348/ho-1-inhibits-preadipocyte-proliferation-and-differentiation-at-the-onset-of-obesity-via-ros-dependent-activation-of-akt2
#5
Gabriel Wagner, Josefine Lindroos-Christensen, Elisa Einwallner, Julia Husa, Thea-Christin Zapf, Katharina Lipp, Sabine Rauscher, Marion Gröger, Andreas Spittler, Robert Loewe, Florian Gruber, J Catharina Duvigneau, Thomas Mohr, Hedwig Sutterlüty-Fall, Florian Klinglmüller, Gerhard Prager, Berthold Huppertz, Jeanho Yun, Oswald Wagner, Harald Esterbauer, Martin Bilban
Excessive accumulation of white adipose tissue (WAT) is a hallmark of obesity. The expansion of WAT in obesity involves proliferation and differentiation of adipose precursors, however, the underlying molecular mechanisms remain unclear. Here, we used an unbiased transcriptomics approach to identify the earliest molecular underpinnings occuring in adipose precursors following a brief HFD in mice. Our analysis identifies Heme Oxygenase-1 (HO-1) as strongly and selectively being upregulated in the adipose precursor fraction of WAT, upon high-fat diet (HFD) feeding...
January 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28078310/polg2-deficiency-causes-adult-onset-syndromic-sensory-neuropathy-ataxia-and-parkinsonism
#6
Lionel Van Maldergem, Arnaud Besse, Boel De Paepe, Emma L Blakely, Vivek Appadurai, Margaret M Humble, Juliette Piard, Kate Craig, Langping He, Pierre Hella, François-Guillaume Debray, Jean-Jacques Martin, Marion Gaussen, Patrice Laloux, Giovanni Stevanin, Rudy Van Coster, Robert W Taylor, William C Copeland, Eric Mormont, Penelope E Bonnen
OBJECTIVE: Mitochondrial dysfunction plays a key role in the pathophysiology of neurodegenerative disorders such as ataxia and Parkinson's disease. We describe an extended Belgian pedigree where seven individuals presented with adult-onset cerebellar ataxia, axonal peripheral ataxic neuropathy, and tremor, in variable combination with parkinsonism, seizures, cognitive decline, and ophthalmoplegia. We sought to identify the underlying molecular etiology and characterize the mitochondrial pathophysiology of this neurological syndrome...
January 2017: Annals of Clinical and Translational Neurology
https://www.readbyqxmd.com/read/28074714/oncocytic-carcinoma-of-the-salivary-gland-in-a-dog
#7
Rei Nakahira, Masaki Michishita, Misaki Kato, Yuki Okuno, Hitoshi Hatakeyama, Hisashi Yoshimura, Daigo Azakami, Kazuhiko Ochiai, Makoto Bonkobara, Kimimasa Takahashi
A 3-y-old male miniature Dachshund was presented with an ~0.8 cm diameter mass in the right mandibular region. Fourteen months later, the mass was 5 × 4 × 3 cm. Grossly, the mass was encapsulated and was homogeneously gray-white on cut surface. Microscopically, the mass was composed of large, round to polygonal tumor cells that were arranged in solid nests and cords separated by a fibrovascular stroma. Tumor cells had large, round, hypochromatic nuclei containing large prominent nucleoli and abundant eosinophilic cytoplasm containing dark blue granules visible with phosphotungstic acid-hematoxylin stain...
January 2017: Journal of Veterinary Diagnostic Investigation
https://www.readbyqxmd.com/read/28060357/the-optical-detection-of-retinal-ganglion-cell-damage
#8
J E Morgan, J Tribble, J Fergusson, N White, I Erchova
We provide an overview of developments in the use optical coherence tomography (OCT) imaging for the detection of retinal ganglion cell (RGC) damage in vivo that avoid use of any exogenous ligands to label cells. The method employs high-resolution OCT using broad spectral light sources to deliver axial resolution of under 5 μm. The resolution approximates that of cellular organelles, which undergo degenerative changes that progress to apoptosis as a result of axon damage. These degenerative changes are manifest as the loss of RGC dendrites and fragmentation of the subcellular network of organelles, in particular, the mitochondria that support dendritic structure...
February 2017: Eye
https://www.readbyqxmd.com/read/28012248/sesamol-ameliorates-diet-induced-obesity-in-c57bl-6j-mice-and-suppresses-adipogenesis-in-3t3-l1-cells-via-regulating-mitochondria-lipid-metabolism
#9
Zhigang Liu, Qinglian Qiao, Yali Sun, Yuwei Chen, Bo Ren, Xuebo Liu
SCOPE: The aim of the current study was to investigate the effect of sesamol, a natural powerful antioxidant and anti-inflammatory phenol derivative of sesame oil, on adiposity and adiposity-related metabolic disturbances in mice fed with western diet, and the potential underlying mechanisms focusing on the mitochondria-lipid metabolism. METHODS & RESULTS: In the experimental model that consisted of 3 month-old C57BL/6J mice divided into 3 groups with/without sesamol in the drinking water including standard diet, high fat and high fructose diet (HFFD), and HFFD with sesamol...
December 24, 2016: Molecular Nutrition & Food Research
https://www.readbyqxmd.com/read/27995753/differential-proteomic-analysis-of-white-adipose-tissues-from-t2d-kkay-mice-by-lc-esi-qtof
#10
Ming Ke, Hanyan Wu, Zhaoyang Zhu, Chi Zhang, Yongqian Zhang, Yunlin Deng
T2D has become a worldwide increasingly social health burden for its high morbidity and heightened prevalence. As one of the main tissues involved in uptake of glucose under the stimulation of insulin, WAT plays very important role in metabolic and homeostasis regulation. We performed a differential proteomics study to investigate alterations in epididymis fat pad of HFD fed T2D KKAy mice compared to normal fed C57BL/6J mice, by (18) O-labeling relative quantitative technique. Among 329 confidently identified proteins, 121 proteins showed significant changes with CV ≤ 20% (fold changes of >2 or <0...
December 20, 2016: Proteomics
https://www.readbyqxmd.com/read/27916644/targeted-mitochondrial-uncoupling-beyond-ucp1-the-fine-line-between-death-and-metabolic-health
#11
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...
March 2017: Biochimie
https://www.readbyqxmd.com/read/27890358/nucleo-mitochondrial-interaction-of-yeast-in-response-to-cadmium-sulfide-quantum-dot-exposure
#12
Francesco Pasquali, Caterina Agrimonti, Luca Pagano, Andrea Zappettini, Marco Villani, Marta Marmiroli, Jason C White, Nelson Marmiroli
Cell sensitivity to quantum dots (QDs) has been attributed to a cascade triggered by oxidative stress leading to apoptosis. The role and function of mitochondria in animal cells are well understood but little information is available on the complex genetic networks that regulate nucleo-mitochondrial interaction. The effect of CdS QD exposure in yeast Saccharomyces cerevisiae was assessed under conditions of limited lethality (<10%), using cell physiological and morphological endpoints. Whole-genomic array analysis and the screening of a deletion mutant library were also carried out...
February 15, 2017: Journal of Hazardous Materials
https://www.readbyqxmd.com/read/27885633/oligodendrocytes-development-physiology-and-glucose-metabolism
#13
Ana I Amaral, Joana M Tavares, Ursula Sonnewald, Mark R N Kotter
The glutamate-glutamine cycle is an outstanding example of how essential neuronal-glial interactions are for brain function. For several decades, this and other metabolic cycles in the brain have only included neurons and astrocytes but not oligodendrocytes, the myelinating cells of the central nervous system (CNS). Recent data revealed that oligodendrocytes are highly metabolically active cells in the brain and, therefore, should not be ignored. Using (13)C-labelled glucose in combination with nuclear magnetic resonance spectroscopy (MRS) and/or mass spectrometry (MS) it is possible to characterize metabolic functions in primary oligodendrocyte cultures...
2016: Advances in Neurobiology
https://www.readbyqxmd.com/read/27875543/irisin-ameliorates-hypoxia-reoxygenation-induced-injury-through-modulation-of-histone-deacetylase-4
#14
Yu Tina Zhao, Hao Wang, Shouyan Zhang, Jianfeng Du, Shougang Zhuang, Ting C Zhao
Irisin is a recently identified myokine which brings increases in energy expenditure and contributes to the beneficial effects of exercise through the browning of white adipose tissues. However, its effects in the heart remains unknown. This study sought to determine the effects of irisin on hypoxia/reoxygenation injury and its relationship with HDAC4. Wild type and stable HDAC4-overexpression cells were generated from H9c2 cardiomyoblasts. HDAC4 overexpression cells and wild type H9c2 cells were exposed to 24 hours of hypoxia followed by one hour of reoxygenation in vitro in the presence or absence of irisin (5 ng/ml)...
2016: PloS One
https://www.readbyqxmd.com/read/27754258/os-36-09-deficiency-of-thermogenesis-and-heat-sensation-accelerates-obesity-and-high-blood-pressure
#15
Yuanting Cui, Li Li, Peng Gao, Liqun Ma, Daoyan Liu, Zhiming Zhu
OBJECTIVE: Obesity is global healthy problem. Uncoupling protein 1 (UCP1) mainly expresses on brown adipose tissue (BAT), uncouples energy substrate oxidation from mitochondrial ATP production and results in the loss of potential energy as heat. Transient receptor potential vanilloid subfamily, member 1 (TRPV1) is the heat-gated cation ion channel. The aim of this study was to investigate the in vivo role of TRPV1 and UCP1 co-action in obesity. DESIGN AND METHOD: We generated and characterized UCP1 mice lacking TRPV1 activity (TRPV1/UCP1 mice)...
September 2016: Journal of Hypertension
https://www.readbyqxmd.com/read/27696117/pathogenic-variants-in-htra2-cause-an-early-onset-mitochondrial-syndrome-associated-with-3-methylglutaconic-aciduria
#16
Monika Oláhová, Kyle Thompson, Steven A Hardy, Inês A Barbosa, Arnaud Besse, Maria-Eleni Anagnostou, Kathryn White, Tracey Davey, Michael A Simpson, Michael Champion, Greg Enns, Susan Schelley, Robert N Lightowlers, Zofia M A Chrzanowska-Lightowlers, Robert McFarland, Charu Deshpande, Penelope E Bonnen, Robert W Taylor
Mitochondrial diseases collectively represent one of the most heterogeneous group of metabolic disorders. Symptoms can manifest at any age, presenting with isolated or multiple-organ involvement. Advances in next-generation sequencing strategies have greatly enhanced the diagnosis of patients with mitochondrial disease, particularly where a mitochondrial aetiology is strongly suspected yet OXPHOS activities in biopsied tissue samples appear normal. We used whole exome sequencing (WES) to identify the molecular basis of an early-onset mitochondrial syndrome-pathogenic biallelic variants in the HTRA2 gene, encoding a mitochondria-localised serine protease-in five subjects from two unrelated families characterised by seizures, neutropenia, hypotonia and cardio-respiratory problems...
January 2017: Journal of Inherited Metabolic Disease
https://www.readbyqxmd.com/read/27679486/identification-of-small-molecule-inhibitors-of-human-cytochrome-c-oxidase-that-target-chemoresistant-glioma-cells
#17
Claudia R Oliva, Tahireh Markert, Larry J Ross, E Lucile White, Lynn Rasmussen, Wei Zhang, Maaike Everts, Douglas R Moellering, Shannon M Bailey, Mark J Suto, Corinne E Griguer
The enzyme cytochrome c oxidase (CcO) or complex IV (EC 1.9.3.1) is a large transmembrane protein complex that serves as the last enzyme in the respiratory electron transport chain of eukaryotic mitochondria. CcO promotes the switch from glycolytic to oxidative phosphorylation (OXPHOS) metabolism and has been associated with increased self-renewal characteristics in gliomas. Increased CcO activity in tumors has been associated with tumor progression after chemotherapy failure, and patients with primary glioblastoma multiforme and high tumor CcO activity have worse clinical outcomes than those with low tumor CcO activity...
November 11, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27643223/os-36-09-deficiency-of-thermogenesis-and-heat-sensation-accelerates-obesity-and-high-blood-pressure
#18
Yuanting Cui, Li Li, Peng Gao, Liqun Ma, Daoyan Liu, Zhiming Zhu
OBJECTIVE: Obesity is global healthy problem. Uncoupling protein 1 (UCP1) mainly expresses on brown adipose tissue (BAT), uncouples energy substrate oxidation from mitochondrial ATP production and results in the loss of potential energy as heat. Transient receptor potential vanilloid subfamily, member 1 (TRPV1) is the heat-gated cation ion channel. The aim of this study was to investigate the in vivo role of TRPV1 and UCP1 co-action in obesity. DESIGN AND METHOD: We generated and characterized UCP1 mice lacking TRPV1 activity (TRPV1/UCP1 mice)...
September 2016: Journal of Hypertension
https://www.readbyqxmd.com/read/27590850/circumventing-the-crabtree-effect-a-method-to-induce-lactate-consumption-and-increase-oxidative-phosphorylation-in-cell-culture
#19
Alexandra I Mot, Jeffrey R Liddell, Anthony R White, Peter J Crouch
Most cells grown in glucose-containing medium generate almost all their ATP via glycolysis despite abundant oxygen supply and functional mitochondria, a phenomenon known as the Crabtree effect. By contrast, most cells within the body rely on mitochondrial oxidative phosphorylation (OXPHOS) to generate the bulk of their energy supply. Thus, when utilising the accessibility of cell culture to elucidate fundamental elements of mitochondria in health and disease, it is advantageous to adopt culture conditions under which the cells have greater reliance upon OXPHOS for the supply of their energy needs...
October 2016: International Journal of Biochemistry & Cell Biology
https://www.readbyqxmd.com/read/27589085/the-cancer-drug-dasatinib-increases-pgc-1%C3%AE-in-adipose-tissue-but-has-adverse-effects-on-glucose-tolerance-in-obese-mice
#20
Lykke Sylow, Jonathan Z Long, Isha A Lokurkar, Xing Zeng, Erik A Richter, Bruce M Spiegelman
Dasatinib (Sprycel) is a tyrosine kinase inhibitor approved for treatment of chronic myeloid leukemia. In this study, we identify dasatinib as a potent inducer of Peroxisome proliferator-activated receptor gamma coactivator (PGC)-1α mRNA. Dasatinib increased PGC-1α mRNA expression up to 6-fold in 3T3-F442A adipocytes, primary adipocytes, and epididymal white adipose tissue from lean and diet-induced obese mice. Importantly, gene expression translated into increased PGC-1α protein content analyzed in melanoma cells and isolated mitochondria from adipocytes...
November 2016: Endocrinology
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