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https://www.readbyqxmd.com/read/29148034/role-of-p62-sqstm1-beyond-autophagy-a-lesson-learned-from-drug-induced-toxicity-in-vitro
#1
Fernando Alegre, Ángela B Moragrega, Miriam Polo, Alberto Marti-Rodrigo, Juan V Esplugues, Ana Blas-Garcia, Nadezda Apostolova
BACKGROUND AND PURPOSE: SQSTM1/p62 is a multifunctional, stress-induced, scaffold protein involved in multiple cellular processes including autophagic clearance, regulation of inflammatory responses and redox homeostasis. Alterations in its function have been associated with a long list of human pathologies such as neurodegenerative, metabolic and bone diseases (down-regulation), and cancerogenesis (up-regulation). However, its role in the off-target effects of clinically used drugs is still not understood...
November 17, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/29119250/microscopy-based-high-throughput-assays-enable-multi-parametric-analysis-to-assess-adverse-effects-of-nanomaterials-in-various-cell-lines
#2
Iris Hansjosten, Juliane Rapp, Luisa Reiner, Ruben Vatter, Susanne Fritsch-Decker, Ravindra Peravali, Taina Palosaari, Elisabeth Joossens, Kirsten Gerloff, Peter Macko, Maurice Whelan, Douglas Gilliland, Isaac Ojea-Jimenez, Marco P Monopoli, Louise Rocks, David Garry, Kenneth Dawson, Peter J F Röttgermann, Alexandra Murschhauser, Joachim O Rädler, Selina V Y Tang, Pete Gooden, Marie-France A Belinga-Desaunay, Abdullah O Khan, Sophie Briffa, Emily Guggenheim, Anastasios Papadiamantis, Iseult Lynch, Eugenia Valsami-Jones, Silvia Diabaté, Carsten Weiss
Manufactured nanomaterials (MNMs) selected from a library of over 120 different MNMs with varied compositions, sizes, and surface coatings were tested by four different laboratories for toxicity by high-throughput/-content (HT/C) techniques. The selected particles comprise 14 MNMs composed of CeO2, Ag, TiO2, ZnO and SiO2 with different coatings and surface characteristics at varying concentrations. The MNMs were tested in different mammalian cell lines at concentrations between 0.5 and 250 µg/mL to link physical-chemical properties to multiple adverse effects...
November 8, 2017: Archives of Toxicology
https://www.readbyqxmd.com/read/29118621/a-new-species-of-trachymyrmex-hymenoptera-formicidae-fungus-growing-ant-from-the-sierra-madre-oriental-of-northeastern-mexico
#3
Sergio R Sánchez-Peña, Manuela Citlali Chacón-Cardosa, Ricardo Canales-Del-Castillo, Lauren Ward, Diana Resendez-Pérez
Here we describe a new species of Trachymyrmex, T. pakawasp. n., from the Gran Sierra Plegada range of the Sierra Madre Oriental, in the states of Coahuila and Nuevo Leon, northeastern Mexico. Trachymyrmex pakawa is a large-sized species compared to other North American Trachymyrmex. Its geographic distribution includes the piedmont of the Gran Sierra Plegada at La Estanzuela, Monterrey, as well as peripheral mountains segregated from the Sierra Madre Oriental (Cerro de las Mitras, Sierra de Zapalinamé, Cañon de San Lorenzo, Cerro de las Letras)...
2017: ZooKeys
https://www.readbyqxmd.com/read/29104541/identification-and-differential-abundance-of-mitochondrial-genome-encoding-small-rnas-mitosrna-in-breast-muscles-of-modern-broilers-and-unselected-chicken-breed
#4
Walter G Bottje, Bhuwan Khatri, Stephanie A Shouse, Dongwon Seo, Barbara Mallmann, Sara K Orlowski, Jeonghoon Pan, Seongbae Kong, Casey M Owens, Nicholas B Anthony, Jae K Kim, Byungwhi C Kong
Background: Although small non-coding RNAs are mostly encoded by the nuclear genome, thousands of small non-coding RNAs encoded by the mitochondrial genome, termed as mitosRNAs were recently reported in human, mouse and trout. In this study, we first identified chicken mitosRNAs in breast muscle using small RNA sequencing method and the differential abundance was analyzed between modern pedigree male (PeM) broilers (characterized by rapid growth and large muscle mass) and the foundational Barred Plymouth Rock (BPR) chickens (characterized by slow growth and small muscle mass)...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/29104227/inter-species-host-gene-expression-differences-in-response-to-human-and-avian-influenza-a-virus-strains
#5
Biruhalem Taye, Dawn Yeo, Raphael Tze Chuen Lee, Boon Huan Tan, Richard J Sugrue, Sebastian Maurer-Stroh
Low pathogenic avian influenza (LPAI) viruses are a source of sporadic human infections and could also contribute to future pandemic outbreaks but little is known about inter-species differences in the host responses to these viruses. Here, we studied host gene expression signatures of cell lines from three species (human, chicken, and canine) in response to six different viruses (H1N1/WSN, H5N2/F59, H5N2/F118, H5N2/F189, H5N3 and H9N2). Comprehensive microarray probe set re-annotation and ortholog mapping of the host genes was necessary to allow comparison over extended functionally annotated gene sets and orthologous pathways...
November 1, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29092635/hydrogen-sulfide-ameliorates-zinc-induced-cell-death-in-neuroblastoma-sh-sy5y-cells
#6
Megumi Shimoji, Hirokazu Hara, Tetsuro Kamiya, Kensuke Okuda, Tetsuo Adachi
Previous reports have demonstrated that excess zinc (Zn(2+)) released from nerve terminals following cerebral ischemia causes brain injury. Therefore, disturbance of Zn(2+) homeostasis in the brain is thought to be closely linked to neurotoxicity. Recently, hydrogen sulfide (H2S), a gaseous mediator, has been reported to ameliorate ischemic brain injury. However, its mechanism is not fully understood. In this study, we examined whether sodium hydrogen sulfide (NaHS), an H2S donor, protects against Zn(2+) cytotoxicity using human neuroblastoma SH-SY5Y cells...
November 1, 2017: Free Radical Research
https://www.readbyqxmd.com/read/29074131/grouper-mavs-functions-as-a-crucial-antiviral-molecule-against-nervous-necrosis-virus-infection
#7
Youhua Huang, Jingcheng Zhang, Zhengliang Ouyang, Jiaxin Liu, Ya Zhang, Yin Hu, Xiaohong Huang, Qiwei Qin
Mitochondrial antiviral signaling protein (MAVS), also known as IPS-1, VISA, and Cardif, has been well studied for its crucial roles in the mammalian interferon immune response. To better understand the actions of MAVS in fish immune response, a MAVS homolog from orange spotted grouper (Epinephelus coioides) (EcMAVS) was cloned and characterized in this study. EcMAVS encoded a 563-amino acid peptide which showed 64% and 20% identity to rock bream (Oplegnathus fasciatus) and human (Homo sapiens), respectively...
October 23, 2017: Fish & Shellfish Immunology
https://www.readbyqxmd.com/read/29054429/surface-chemistry-induces-mitochondria-mediated-apoptosis-of-breast-cancer-cells-via-pten-pi3k-akt-signaling-pathway
#8
Jing Zhang, Li Li, Yueting Peng, Yu Chen, Xiaoying Lv, Shun Li, Xiang Qin, Hong Yang, Chunhui Wu, Yiyao Liu
Tumor cell can be significantly influenced by various chemical groups of the extracellular matrix proteins. However, the underlying molecular mechanisms involved in the interaction between cancer cells and functional groups in the extracellular matrix remain unknown. Using chemically modified surfaces with biological functional groups (CH3, NH2, OH), it was found that hydrophobic surfaces modified with CH3 and NH2 suppressed cell proliferation and induced the number of apoptotic cells. Mitochondrial dysfunction, cytochrome c release, Bax upregulation, cleaved caspase-3 and PARP, and Bcl-2 downregulation indicated that hydrophobic surfaces with CH3 and NH2 triggered the activation of intrinsic apoptotic signaling pathway...
October 17, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29039493/actein-induces-apoptosis-in-leukemia-cells-through-suppressing-rhoa-rock1-signaling-pathway
#9
Wen-Di Zhou, Xiang Wang, Xing-Zhen Sun, Jian Hu, Rong-Rong Zhang, Ze Hong
Actein is a tetracyclic triterpenoid compound, extracted from the rhizome of Cimicifuga foetida, exhibiting anticancer activities as previously reported. However, the effects of actein on human leukemia have not been explored before. In this study, the role of actein in regulating apoptosis induction in human leukemia cells was investigated. Actein administration significantly enhanced apoptosis, especially in human leukemia cell line of U937 and the primary human leukemia cells. The promotion was accompanied by caspase-9, caspase-3 and poly(ADP-ribose) polymerase (PARP) cleavage, and cytochrome c (Cyto-c) release...
October 10, 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/28988798/differential-carbonylation-of-proteins-in-end-stage-human-fatty-and-nonfatty-nash
#10
Colin T Shearn, Laura M Saba, James R Roede, David J Orlicky, Alisabeth H Shearn, Dennis R Petersen
OBJECTIVE: In the liver, a contributing factor in the pathogenesis of non-alcoholic fatty liver disease is oxidative stress leading to the accumulation of highly reactive electrophilic α/β unsaturated aldehydes. The objective of this study was to determine if significant differences were evident when evaluating carbonylation in human end-stage fatty nonalcoholic steatohepatitis (fNASH) compared to end-stage nonfatty NASH (nfNASH). METHODS: Using hepatic tissue obtained from healthy humans and patients diagnosed with end stage nfNASH or fNASH, overall carbonylation was assessed by immunohistochemistry (IHC) and LC-MS/MS followed by bioinformatics...
October 6, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28982073/cardiac-specific-inactivation-of-lpp3-in-mice-leads-to-myocardial-dysfunction-and-heart-failure
#11
Mini Chandra, Diana Escalante-Alcalde, Md Shenuarin Bhuiyan, Anthony Wayne Orr, Christopher Kevil, Andrew J Morris, Hyung Nam, Paari Dominic, Kevin J McCarthy, Sumitra Miriyala, Manikandan Panchatcharam
Lipid Phosphate phosphatase 3 (LPP3), encoded by the Plpp3 gene, is an enzyme that dephosphorylates the bioactive lipid mediator lysophosphatidic acid (LPA). To study the role of LPP3 in the myocardium, we generated a cardiac specific Plpp3 deficient mouse strain. Although these mice were viable at birth in contrast to global Plpp3 knockout mice, they showed increased mortality ~ 8 months. LPP3 deficient mice had enlarged hearts with reduced left ventricular performance as seen by echocardiography. Cardiac specific Plpp3 deficient mice had longer ventricular effective refractory periods compared to their Plpp3 littermates...
September 28, 2017: Redox Biology
https://www.readbyqxmd.com/read/28977846/downregulation-of-x-linked-inhibitor-of-apoptosis-protein-by-7-benzylidenenaltrexone-maleate-sensitizes-pancreatic-cancer-cells-to-trail-induced-apoptosis
#12
So Young Kim, Sojung Park, SeonA Yoo, Jin Kyung Rho, Eun Sung Jun, Suhwan Chang, Kyung Kon Kim, Song Cheol Kim, Inki Kim
Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a potential biological anticancer agent. However, a wide range of human primary cancers, including pancreatic cancer, display resistance to apoptosis induction by TRAIL. Therefore, this resistance needs to be overcome to allow TRAIL to be successfully used in cancer therapy. In this study, we performed a compound screen to isolate TRAIL sensitizers and found that one of the identified compounds, 7-benzylidenenaltrexone maleate (BNTX), sensitized pancreatic cancer cells to TRAIL-induced apoptotic cell death...
September 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28974722/succinate-promotes-stem-cell-migration-through-the-gpr91-dependent-regulation-of-drp1-mediated-mitochondrial-fission
#13
So Hee Ko, Gee Euhn Choi, Ji Young Oh, Hyun Jik Lee, Jun Sung Kim, Chang Woo Chae, Diana Choi, Ho Jae Han
The role of metabolites produced from stem cell metabolism has been emerged as signaling molecules to regulate stem cell behaviors such as migration. The mitochondrial morphology is closely associated with the metabolic balance and stem cell function. However, the physiological role of succinate on human mesenchymal stem cell (hMSC) migration by regulating the mitochondrial morphology remains unclear. Here, we investigate the effect of succinate on hMSC migration via regulation of mitochondrial dynamics and its related signaling pathway...
October 3, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28973175/amyotrophic-lateral-sclerosis-associated-mutant-sod1-inhibits-anterograde-axonal-transport-of-mitochondria-by-reducing-miro1-levels
#14
Annekathrin Moller, Claudia S Bauer, Rebecca N Cohen, Christopher P Webster, Kurt J De Vos
Defective axonal transport is an early neuropathological feature of amyotrophic lateral sclerosis (ALS). We have previously shown that ALS-associated mutations in Cu/Zn superoxide dismutase 1 (SOD1) impair axonal transport of mitochondria in motor neurons isolated from SOD1 G93A transgenic mice and in ALS mutant SOD1 transfected cortical neurons, but the underlying mechanisms remained unresolved.The outer mitochondrial membrane protein mitochondrial Rho GTPase 1 (Miro1) is a master regulator of mitochondrial axonal transport in response to cytosolic calcium (Ca2+) levels ([Ca2+]c) and mitochondrial damage...
September 14, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28970150/flcn-the-causative-gene-for-birt-hogg-dub%C3%A3-syndrome
#15
REVIEW
Laura S Schmidt, W Marston Linehan
Germline mutations in the novel tumor suppressor gene FLCN are responsible for the autosomal dominant inherited disorder Birt-Hogg-Dubé (BHD) syndrome that predisposes to fibrofolliculomas, lung cysts and spontaneous pneumothorax, and an increased risk for developing kidney tumors. Although the encoded protein, folliculin (FLCN), has no sequence homology to known functional domains, x-ray crystallographic studies have shown that the C-terminus of FLCN has structural similarity to DENN (differentially expressed in normal cells and neoplasia) domain proteins that act as guanine nucleotide exchange factors (GEFs) for small Rab GTPases...
January 15, 2018: Gene
https://www.readbyqxmd.com/read/28961892/plasma-mitochondrial-dna-levels-are-inversely-associated-with-hiv-rna-levels-and-directly-with-cd4-counts-potential-role-as-a-biomarker-of-hiv-replication
#16
Berta Pernas, Ignacio Rego-Pérez, Andrés Tabernilla, Vanesa Balboa, Sara Relaño, Marta Grandal, Manuel Crespo, Álvaro Mena, Ángeles Castro-Iglesias, Francisco J Blanco, Eva Poveda
Objectives: To evaluate plasma mitochondrial DNA (mtDNA) levels among HIV-infected patients and its potential role as a biomarker of residual viral replication. Methods: HIV-infected patients on follow-up at a reference hospital in north-west Spain were selected. DNA was isolated from plasma samples and mtDNA levels were assessed using a quantitative real-time PCR assay. HIV-RNA levels and CD4+ cell counts were evaluated in the same blood samples used for plasma mtDNA quantification...
November 1, 2017: Journal of Antimicrobial Chemotherapy
https://www.readbyqxmd.com/read/28953378/discovery-of-a-potent-and-specific-m-tuberculosis-leucyl-trna-synthetase-inhibitor-s-3-aminomethyl-4-chloro-7-2-hydroxyethoxy-benzo-c-1-2-oxaborol-1-3h-ol-gsk656
#17
Xianfeng Li, Vincent Hernandez, Fernando L Rock, Wai Choi, Yvonne S L Mak, Manisha Mohan, Weimin Mao, Yasheen Zhou, Eric E Easom, Jacob J Plattner, Wuxin Zou, Esther Pérez-Herrán, Ilaria Giordano, Alfonso Mendoza-Losana, Carlos Alemparte, Joaquín Rullas, Iñigo Angulo-Barturen, Sabrinia Crouch, Fátima Ortega, David Barros, M R K Alley
There is an urgent need to develop new and safer antitubercular agents that possess a novel mode of action. We synthesized and evaluated a novel series of 3-aminomethyl 4-halogen benzoxaboroles as Mycobacterium tuberculosis (Mtb) leucyl-tRNA synthetase (LeuRS) inhibitors. A number of Mtb LeuRS inhibitors were identified that demonstrated good antitubercular activity with high selectivity over human mitochondrial and cytoplasmic LeuRS. Further evaluation of these Mtb LeuRS inhibitors by in vivo pharmacokinetics (PK) and murine tuberculosis (TB) efficacy models led to the discovery of GSK3036656 (abbreviated as GSK656)...
October 12, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28920922/g%C3%AE-13-ablation-reprograms-myofibers-to-oxidative-phenotype-and-enhances-whole-body-metabolism
#18
Ja Hyun Koo, Tae Hyun Kim, Shi-Young Park, Min Sung Joo, Chang Yeob Han, Cheol Soo Choi, Sang Geon Kim
Skeletal muscle is a key organ in energy homeostasis owing to its high requirement for nutrients. Heterotrimeric G proteins converge signals from cell-surface receptors to potentiate or blunt responses against environmental changes. Here, we show that muscle-specific ablation of Gα13 in mice promotes reprogramming of myofibers to the oxidative type, with resultant increases in mitochondrial biogenesis and cellular respiration. Mechanistically, Gα13 and its downstream effector RhoA suppressed nuclear factor of activated T cells 1 (NFATc1), a chief regulator of myofiber conversion, by increasing Rho-associated kinase 2-mediated (Rock2-mediated) phosphorylation at Ser243...
October 2, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28910691/phylogeny-and-taxonomy-of-new-and-re-examined-strains-of-tubulinea-amoebozoa
#19
Tomáš Tyml, Iva Dyková
Morphological and molecular characterizations of three newly isolated tubulinean strains and re-examination of five strains formerly considered representatives of Saccamoeba and one strain formerly considered as Trichamoeba resulted in (a) the determination of strain BA02, isolated from a dripping rock ledge in Skansbukta (Billefjorden, Svalbard), as a new representative of Ptolemeba bulliensis Brown et al., 2014; (b) identification of strain ATCC(®) 50249™, deposited in the American Type Culture Collection as Trichamoeba, as the same species (P...
August 26, 2017: European Journal of Protistology
https://www.readbyqxmd.com/read/28899515/the-water-extract-of-liuwei-dihuang-possesses-multi-protective-properties-on-neurons-and-muscle-tissue-against-deficiency-of-survival-motor-neuron-protein
#20
Yu-Ting Tseng, Yuh-Jyh Jong, Wei-Fang Liang, Fang-Rong Chang, Yi-Ching Lo
BACKGROUND: Deficiency of survival motor neuron (SMN) protein, which is encoded by the SMN1 and SMN2 genes, induces widespread splicing defects mainly in spinal motor neurons, and leads to spinal muscular atrophy (SMA). Currently, there is no effective treatment for SMA. Liuwei dihuang (LWDH), a traditional Chinese herbal formula, possesses multiple therapeutic benefits against various diseases via modulation of the nervous, immune and endocrine systems. Previously, we demonstrated water extract of LWDH (LWDH-WE) protects dopaminergic neurons and improves motor activity in models of Parkinson's disease...
October 15, 2017: Phytomedicine: International Journal of Phytotherapy and Phytopharmacology
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