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https://www.readbyqxmd.com/read/28213273/2-methoxyestradiol-protects-against-ischemia-reperfusion-injury-in-alcoholic-fatty-liver-by-enhancing-sirtuin-1-mediated-autophagy
#1
Hong-Ik Cho, Min-Jong Seo, Sun-Mee Lee
Alcoholic fatty liver (AFL) is susceptible to ischemia/reperfusion (I/R) injury, responding with inflammation and extensive hepatocellular damage. Autophagy maintains cellular homeostasis and regulates inflammation and lipid metabolism. 2-Methoxyestradiol (2-ME2), an endogenous metabolite of estradiol, exhibits antioxidant and anti-inflammatory properties. This study examined the cytoprotective mechanisms of 2-ME2 on hepatic I/R in AFL, focusing on autophagy signaling. C57BL/6 mice were fed an ethanol diet (ED) to induce AFL, or a control diet (CD) for 6 weeks, and then subjected to 60 min of ischemia and 5 h of reperfusion...
February 14, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/28213158/pink1-parkin-mitophagy-and-neurodegeneration-what-do-we-really-know-in-vivo
#2
REVIEW
Alexander J Whitworth, Leo J Pallanck
Mitochondria are essential organelles that provide cellular energy and buffer cytoplasmic calcium. At the same time they produce damaging reactive oxygen species and sequester pro-apoptotic factors. Hence, eukaryotes have evolved exquisite homeostatic processes that maintain mitochondrial integrity, or ultimately remove damaged organelles. This subject has garnered intense interest recently following the discovery that two Parkinson's disease genes, PINK1 and parkin, regulate mitochondrial degradation (mitophagy)...
February 14, 2017: Current Opinion in Genetics & Development
https://www.readbyqxmd.com/read/28213071/pla2g6-accumulates-in-lewy-bodies-in-park14-and-idiopathic-parkinson-s-disease
#3
Yasuo Miki, Kunikazu Tanji, Fumiaki Mori, Akiyoshi Kakita, Hitoshi Takahashi, Koichi Wakabayashi
The histopathological hallmark of Parkinson's disease (PD) and dementia with Lewy bodies (DLB) is the occurrence of insoluble fibrillary aggregates known as Lewy bodies, in which phosphorylated α-synuclein (α-syn) is a major component. To date, familial PD-linked gene products, including α-syn, parkin, PINK-1, DJ-1 and LRRK2, are known to be involved in Lewy body formation. Phospholipase A2, group VI (PLA2G6) is the causative gene for PARK14-linked parkinsonism (PARK14), a familial form of juvenile-onset dystonia parkinsonism...
February 14, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/28211874/datf4-regulation-of-mitochondrial-folate-mediated-one-carbon-metabolism-is-neuroprotective
#4
Ivana Celardo, Susann Lehmann, Ana C Costa, Samantha Hy Loh, L Miguel Martins
Neurons rely on mitochondria as their preferred source of energy. Mutations in PINK1 and PARKIN cause neuronal death in early-onset Parkinson's disease (PD), thought to be due to mitochondrial dysfunction. In Drosophila pink1 and parkin mutants, mitochondrial defects lead to the compensatory upregulation of the mitochondrial one-carbon cycle metabolism genes by an unknown mechanism. Here we uncover that this branch is triggered by the activating transcription factor 4 (ATF4). We show that ATF4 regulates the expression of one-carbon metabolism genes SHMT2 and NMDMC as a protective response to mitochondrial toxicity...
February 17, 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/28211011/teoa-a-triterpenoid-from-actinidia-eriantha-induces-autophagy-in-sw620-cells-via-endoplasmic-reticulum-stress-and-ros-dependent-mitophagy
#5
Dandan Zhang, Cuixia Gao, Ruyi Li, Lin Zhang, Jingkui Tian
2α,3α,24-Thrihydroxyurs-12-en-28-oicacid (TEOA), a pentacyclic triterpenoid, isolated from the roots of Actinidia eriantha, exhibits significant cytotoxicity against SW620, BGC-823, HepG-2, A549 and PC-3 cancer cells. In this study, we investigated the underlying molecular mechanism of the anticancer activity of TEOA in SW620 cells. We demonstrated that TEOA induced apoptosis through cleavage of caspase-9 and PARP in SW620 cells. In addition, evidence of TEOA-mediated autophagy included the induction of autophagolysosomes and activation of autophagic markers LC-3B and p62...
February 16, 2017: Archives of Pharmacal Research
https://www.readbyqxmd.com/read/28205494/language-deficits-as-a-preclinical-window-into-parkinson-s-disease-evidence-from-asymptomatic-parkin-and-dardarin-mutation-carriers
#6
Adolfo M García, Lucas Sedeño, Natalia Trujillo, Yamile Bocanegra, Diana Gomez, David Pineda, Andrés Villegas, Edinson Muñoz, William Arias, Agustín Ibáñez
OBJECTIVES: The worldwide spread of Parkinson's disease (PD) calls for sensitive and specific measures enabling its early (or, ideally, preclinical) detection. Here, we use language measures revealing deficits in PD to explore whether similar disturbances are present in asymptomatic individuals at risk for the disease. METHODS: We administered executive, semantic, verb-production, and syntactic tasks to sporadic PD patients, genetic PD patients with PARK2 (parkin) or LRRK2 (dardarin) mutation, asymptomatic first-degree relatives of the latter with similar mutations, and socio-demographically matched controls...
February 2017: Journal of the International Neuropsychological Society: JINS
https://www.readbyqxmd.com/read/28198608/high-throughput-continuous-hydrothermal-synthesis-of-transparent-conducting-aluminium-and-gallium-co-doped-zinc-oxides
#7
Dougal Peter Howard, Peter Marchand, Liam McCafferty, Claire J Carmalt, Ivan P Parkin, Jawwad A Darr
High-throughput continuous hydrothermal flow synthesis was used to generate a library of aluminium and gallium co-doped zinc oxide nanoparticles of specific atomic ratios. Resistivities of the materials were determined by Hall Effect measurements on heat-treated pressed discs and the results collated into a resistivity-composition map. Optimal resis-tivities of ca. 9 x 10-3 Ω cm were reproducibly achieved for several samples e.g. co-doped ZnO with 2 at% Ga and 1 at% Al. The optimum sample on balance of performance and cost was deemed to be ZnO co-doped with 3 at% Al and 1 at% Ga...
February 15, 2017: ACS Combinatorial Science
https://www.readbyqxmd.com/read/28187531/cutaneous-melanoma-attributable-to-solar-radiation-in-cali-colombia
#8
Esther de Vries, Julio R Amador, Carlos Javier Rincon, Claudia Uribe, D Maxwell Parkin
Estimating the population attributable fraction (PAF) of melanomas due to sun exposure is challenging as there are no unexposed population nor reliable exposure data. In high incidence countries, a historic cohort of the South Thames cancer registry was used as a minimally exposed population using the formula PAF = (observed incidence-incidence in minimally exposure)/observed incidence. In this study we apply this method, constructing a minimally exposed cohort for Colombia and also using the historical South Thames data, using melanoma incidence data from the population-based cancer registry of Cali, Colombia for the period 1967-2012...
February 10, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/28178523/the-mitochondrial-rhomboid-protease-parl-is-regulated-by-pdk2-to-integrate-mitochondrial-quality-control-and-metabolism
#9
Guang Shi, G Angus McQuibban
Mitochondrial quality control (MQC) systems are essential for mitochondrial health and normal cellular function. Dysfunction of MQC is emerging as a central mechanism for the pathogenesis of various diseases, including Parkinson's disease. The mammalian mitochondrial rhomboid protease, PARL, has been proposed as a regulator of PINK1/PARKIN-mediated mitophagy, which is an essential component of MQC. PARL undergoes an N-terminal autocatalytic cleavage (β cleavage), which is required for efficient mitophagy...
February 7, 2017: Cell Reports
https://www.readbyqxmd.com/read/28171547/cystic-fibrosis-gene-modifier-slc26a9-modulates-airway-response-to-cftr-directed-therapeutics
#10
Lisa J Strug, Tanja Gonska, Gengming He, Katherine Keenan, Wan Ip, Pierre-Yves Boëlle, Fan Lin, Naim Panjwani, Jiafen Gong, Weili Li, David Soave, Bowei Xiao, Elizabeth Tullis, Harvey Rabin, Michael D Parkins, April Price, Peter C Zuberbuhler, Harriet Corvol, Felix Ratjen, Lei Sun, Christine E Bear, Johanna M Rommens
No abstract text is available yet for this article.
October 15, 2016: Human Molecular Genetics
https://www.readbyqxmd.com/read/28169962/parkin-mediates-neuroprotection-through-activation-of-notch1-signaling
#11
Ji-Hye Yoon, Eun-Jung Ann, Mi-Yeon Kim, Ji-Seon Ahn, Eun-Hye Jo, Hye-Jin Lee, Hye-Won Lee, Young Chul Lee, Jeong-Sun Kim, Hee-Sae Park
Parkin, an E3 ubiquitin ligase, is the most frequently mutated gene in hereditary Parkinson's disease. Inactivation of Parkin leads to impairment of the ubiquitin-proteasome system, resulting in the accumulation of misfolded or aggregated proteins and ensuing neurodegeneration. In this study, we show that Parkin positively regulates the Notch1 signaling pathway. Overexpression of Parkin stabilized Notch1-IC protein levels, whereas knockdown of Parkin decreased Notch1-IC protein stability. Notably, overexpression of Parkin disrupted oxidative stress-induced apoptosis in neuronal cells...
February 4, 2017: Neuroreport
https://www.readbyqxmd.com/read/28165849/autophagosome-formation-and-cargo-sequestration-in-the-absence-of-lc3-gabaraps
#12
Benjamin Scott Padman, Thanh Ngoc Nguyen, Michael Lazarou
It has been widely assumed that Atg8 family LC3/GABARAP proteins are essential for the formation of autophagosomes during macroautophagy/autophagy, and the sequestration of cargo during selective autophagy. However, there is little direct evidence on the functional contribution of these proteins to autophagosome biogenesis in mammalian cells. To dissect the functions of LC3/GABARAPs during starvation-induced autophagy and PINK1-PARK2/Parkin-dependent mitophagy, we utilized CRISPR/Cas9 gene editing to generate knockouts of the LC3 and GABARAP subfamilies, and all 6 Atg8 family proteins in HeLa cells...
February 6, 2017: Autophagy
https://www.readbyqxmd.com/read/28140487/mccrearamycins-a-d-geldanamycin-derived-cyclopentenone-macrolactams-from-an-eastern-kentucky-abandoned-coal-mine-microbe
#13
Xiachang Wang, Yinan Zhang, Larissa V Ponomareva, Qingchao Qiu, Ryan Woodcock, Sherif I Elshahawi, Xiabin Chen, Ziyuan Zhou, Bruce E Hatcher, James C Hower, Chang-Guo Zhan, Sean Parkin, Madan K Kharel, S Randal Voss, Khaled A Shaaban, Jon S Thorson
Four cyclopentenone-containing ansamycin polyketides (mccrearamycins A-D), and six new geldanamycins (Gdms B-G, including new linear and mycothiol conjugates), were characterized as metabolites of Streptomyces sp. AD-23-14 isolated from the Rock Creek underground coal mine acid drainage site. Biomimetic chemical conversion studies using both simple synthetic models and Gdm D confirmed that the mccrearamycin cyclopentenone derives from benzilic acid rearrangement of 19-hydroxy Gdm, and thereby provides a new synthetic derivatization strategy and implicates a potential unique biocatalyst in mccrearamycin cyclopentenone formation...
January 31, 2017: Angewandte Chemie
https://www.readbyqxmd.com/read/28134239/a-rab5-endosomal-pathway-mediates-parkin-dependent-mitochondrial-clearance
#14
Babette C Hammerling, Rita H Najor, Melissa Q Cortez, Sarah E Shires, Leonardo J Leon, Eileen R Gonzalez, Daniela Boassa, Sébastien Phan, Andrea Thor, Rebecca E Jimenez, Hong Li, Richard N Kitsis, Gerald W Dorn Ii, Junichi Sadoshima, Mark H Ellisman, Åsa B Gustafsson
Damaged mitochondria pose a lethal threat to cells that necessitates their prompt removal. The currently recognized mechanism for disposal of mitochondria is autophagy, where damaged organelles are marked for disposal via ubiquitylation by Parkin. Here we report a novel pathway for mitochondrial elimination, in which these organelles undergo Parkin-dependent sequestration into Rab5-positive early endosomes via the ESCRT machinery. Following maturation, these endosomes deliver mitochondria to lysosomes for degradation...
January 30, 2017: Nature Communications
https://www.readbyqxmd.com/read/28131082/mitochondrial-dynamics-in-type-2-diabetes-pathophysiological-implications
#15
REVIEW
Susana Rovira-Llopis, Celia Bañuls, Noelia Diaz-Morales, Antonio Hernandez-Mijares, Milagros Rocha, Victor M Victor
Mitochondria play a key role in maintaining cellular metabolic homeostasis. These organelles have a high plasticity and are involved in dynamic processes such as mitochondrial fusion and fission, mitophagy and mitochondrial biogenesis. Type 2 diabetes is characterised by mitochondrial dysfunction, high production of reactive oxygen species (ROS) and low levels of ATP. Mitochondrial fusion is modulated by different proteins, including mitofusin-1 (MFN1), mitofusin-2 (MFN2) and optic atrophy (OPA-1), while fission is controlled by mitochondrial fission 1 (FIS1), dynamin-related protein 1 (DRP1) and mitochondrial fission factor (MFF)...
January 16, 2017: Redox Biology
https://www.readbyqxmd.com/read/28129614/effects-of-titanium-dioxide-nanoparticles-exposure-on-parkinsonism-in-zebrafish-larvae-and-pc12
#16
Qinglian Hu, Fengliang Guo, Fenghui Zhao, Zhengwei Fu
Nanomaterials hold significant potential for industrial and biomedical application these years. Therefore, the relationship between nanoparticles and neurodegenerative disease is of enormous interest. In this contribution, zebrafish embryos and PC12 cell lines were selected for studying neurotoxicity of titanium dioxide nanoparticles (TiO2 NPs). After exposure of different concentrations of TiO2 NPs to embryos from fertilization to 96 hpf, the hatching time of zebrafish was decreased, accompanied by an increase in malformation rate...
January 16, 2017: Chemosphere
https://www.readbyqxmd.com/read/28126444/effect-of-freezing-sputum-on-pseudomonas-aeruginosa-population-heterogeneity
#17
Ali Poonja, Alya Heirali, Matthew Workentine, Douglas G Storey, Ranjani Somayaji, Harvey R Rabin, Michael G Surette, Michael D Parkins
Pseudomonas aeruginosa develops profound population heterogeneity in CF airways. How changes in these populations relate to clinical status is unknown. In order to facilitate this understanding, frequent sampling of this community is required. To determine if the collection and storage of sputum at home may pose a viable option, we collected sputum from ten patients. Sputum samples were partitioned in two, with half immediately processed on MacConkey agar and half assessed after freezing for one week in a home-freezer...
January 23, 2017: Journal of Cystic Fibrosis: Official Journal of the European Cystic Fibrosis Society
https://www.readbyqxmd.com/read/28125779/monolayer-ws2-nanopores-for-dna-translocation-with-light-adjustable-sizes
#18
Gopinath Danda, Paul Masih Das, Yung-Chien Chou, Jerome T Mlack, William M Parkin, Carl H Naylor, Kazunori Fujisawa, Tianyi Zhang, Laura Beth Fulton, Mauricio Terrones, Alan T Charlie Johnson, Marija Drndić
Two-dimensional materials are promising for a range of applications, as well as testbeds for probing the physics of low-dimensional systems. Tungsten disulfide (WS2) monolayers exhibit a direct band gap and strong photoluminescence (PL) in the visible range, opening possibilities for advanced optoelectronic applications. Here, we report the realization of two-dimensional nanometer-size pores in suspended monolayer WS2 membranes, allowing for electrical and optical response in ionic current measurements. A focused electron beam was used to fabricate nanopores in WS2 membranes suspended on silicon-based chips and characterized using PL spectroscopy and aberration-corrected high-resolution scanning transmission electron microscopy...
February 1, 2017: ACS Nano
https://www.readbyqxmd.com/read/28124127/acute-low-intensity-cycling-with-blood-flow-restriction-has-no-effect-on-metabolic-signaling-in-human-skeletal-muscle-compared-to-traditional-exercise
#19
William J Smiles, Miguel S Conceição, Guilherme D Telles, Mara P T Chacon-Mikahil, Cláudia R Cavaglieri, Felipe C Vechin, Cleiton A Libardi, John A Hawley, Donny M Camera
PURPOSE: Autophagy is an intracellular degradative system sensitive to hypoxia and exercise-induced perturbations to cellular bioenergetics. We determined the effects of low-intensity endurance-based exercise performed with blood-flow restriction (BFR) on cell signaling adaptive responses regulating autophagy and substrate metabolism in human skeletal muscle. METHODS: In a randomized cross-over design, nine young, healthy but physically inactive males completed three experimental trials separated by 1 week of recovery consisting of either a resistance exercise bout (REX: 4 × 10 leg press repetitions, 70% 1-RM), endurance exercise (END: 30 min cycling, 70% VO2peak), or low-intensity cycling with BFR (15 min, 40% VO2peak)...
January 25, 2017: European Journal of Applied Physiology
https://www.readbyqxmd.com/read/28122242/pink1-primes-parkin-mediated-ubiquitination-of-paris-in-dopaminergic-neuronal-survival
#20
Yunjong Lee, Daniel A Stevens, Sung-Ung Kang, Haisong Jiang, Yun-Il Lee, Han Seok Ko, Leslie A Scarffe, George E Umanah, Hojin Kang, Sangwoo Ham, Tae-In Kam, Kathleen Allen, Saurav Brahmachari, Jungwoo Wren Kim, Stewart Neifert, Seung Pil Yun, Fabienne C Fiesel, Wolfdieter Springer, Valina L Dawson, Joo-Ho Shin, Ted M Dawson
Mutations in PTEN-induced putative kinase 1 (PINK1) and parkin cause autosomal-recessive Parkinson's disease through a common pathway involving mitochondrial quality control. Parkin inactivation leads to accumulation of the parkin interacting substrate (PARIS, ZNF746) that plays an important role in dopamine cell loss through repression of proliferator-activated receptor gamma coactivator-1-alpha (PGC-1α) promoter activity. Here, we show that PARIS links PINK1 and parkin in a common pathway that regulates dopaminergic neuron survival...
January 24, 2017: Cell Reports
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