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https://www.readbyqxmd.com/read/28732355/checkpoint-kinase-1-inhibition-sensitises-transformed-cells-to-dihydroorotate-dehydrogenase-inhibition
#1
Stéphanie Arnould, Geneviève Rodier, Gisèle Matar, Charles Vincent, Nelly Pirot, Yoann Delorme, Charlène Berthet, Yoan Buscail, Jean Yohan Noël, Simon Lachambre, Marta Jarlier, Florence Bernex, Hélène Delpech, Pierre Olivier Vidalain, Yves L Janin, Charles Theillet, Claude Sardet
Reduction in nucleotide pools through the inhibition of mitochondrial enzyme dihydroorotate dehydrogenase (DHODH) has been demonstrated to effectively reduce cancer cell proliferation and tumour growth. The current study sought to investigate whether this antiproliferative effect could be enhanced by combining Chk1 kinase inhibition. The pharmacological activity of DHODH inhibitor teriflunomide was more selective towards transformed mouse embryonic fibroblasts than their primary or immortalised counterparts, and this effect was amplified when cells were subsequently exposed to PF477736 Chk1 inhibitor...
July 12, 2017: Oncotarget
https://www.readbyqxmd.com/read/28732339/aryl-and-alkyl-phosphorus-containing-flame-retardants-induced-mitochondrial-impairment-and-cell-death-in-chinese-hamster-ovary-cho-k1-cells
#2
Chao Huang, Na Li, Shengwu Yuan, Xiaoya Ji, Mei Ma, Kaifeng Rao, Zijian Wang
Phosphorus-containing flame retardants (PFRs) are increasingly in demand worldwide as replacements for brominated flame retardants (BFRs), but insufficient available toxicological information on PFRs makes assessing their health risks challenging. Mitochondria are important targets of various environmental pollutants, and mitochondrial dysfunction may lead to many common diseases. In the present study, mitochondria impairment-related endpoints were measured by a high content screening (HCS) assay for 11 selected non-halogen PFRs in Chinese hamster ovary (CHO-k1) cells...
July 18, 2017: Environmental Pollution
https://www.readbyqxmd.com/read/28732308/ripk3-induces-mitochondrial-apoptosis-via-inhibition-of-fundc1-mitophagy-in-cardiac-ir-injury
#3
Hao Zhou, Pingjun Zhu, Jun Guo, Nan Hu, Shuyi Wang, Dandan Li, Shunying Hu, Jun Ren, Feng Cao, Yundai Chen
Ripk3-required necroptosis and mitochondria-mediated apoptosis are the predominant types of cell death that largely account for the development of cardiac ischemia reperfusion injury (IRI). Here, we explored the effect of Ripk3 on mitochondrial apoptosis. Compared with wild-type mice, the infarcted area in Ripk3-deficient (Ripk3(-/-)) mice had a relatively low abundance of apoptotic cells. Moreover, the loss of Ripk3 protected the mitochondria against IRI and inhibited caspase9 apoptotic pathways. These protective effects of Ripk3 deficiency were relied on mitophagy activation...
July 13, 2017: Redox Biology
https://www.readbyqxmd.com/read/28732239/effects-of-antiepileptic-drugs-on-mitochondrial-functions-morphology-kinetics-biogenesis-and-survival
#4
REVIEW
Josef Finsterer, Fulvio A Scorza
OBJECTIVES: Antiepileptic drugs (AEDs) exhibit adverse and beneficial effects on mitochondria, which have a strong impact on the treatment of patients with a mitochondrial disorder (MID) with epilepsy (mitochondrial epilepsy). This review aims at summarizing and discussing recent findings concerning the effect of AEDs on mitochondrial functions and the clinical consequences with regard to therapy of mitochondrial epilepsy and of MIDs in general. METHODS: Literature review...
July 13, 2017: Epilepsy Research
https://www.readbyqxmd.com/read/28732215/a-method-for-next-generation-sequencing-of-paired-diagnostic-and-remission-samples-to-detect-mitochondrial-dna-mutations-associated-with-leukemia
#5
Ilaria S Pagani, Chung H Kok, Verity A Saunders, Mark B Van der Hoek, Susan L Heatley, Anthony P Schwarer, Christopher N Hahn, Timothy P Hughes, Deborah L White, David M Ross
Somatic mitochondrial DNA (mtDNA) mutations have been identified in many human cancers, including leukemia. To identify somatic mutations, it is necessary to have a control tissue from the same individual for comparison. When patients with leukemia achieve remission, the remission peripheral blood may be a suitable and easily accessible control tissue, but this approach has not previously been applied to the study of mtDNA mutations. We have developed and validated a next-generation sequencing approach for the identification of leukemia-associated mtDNA mutations in 26 chronic myeloid leukemia patients at diagnosis using either nonhematopoietic or remission blood samples as the control...
July 18, 2017: Journal of Molecular Diagnostics: JMD
https://www.readbyqxmd.com/read/28732079/lmp1-mediated-glycolysis-induces-myeloid-derived-suppressor-cell-expansion-in-nasopharyngeal-carcinoma
#6
Ting-Ting Cai, Shu-Biao Ye, Yi-Na Liu, Jia He, Qiu-Yan Chen, Hai-Qiang Mai, Chuan-Xia Zhang, Jun Cui, Xiao-Shi Zhang, Pierre Busson, Yi-Xin Zeng, Jiang Li
Myeloid-derived suppressor cells (MDSCs) are expanded in tumor microenvironments, including that of Epstein-Barr virus (EBV)-associated nasopharyngeal carcinoma (NPC). The link between MDSC expansion and EBV infection in NPC is unclear. Here, we show that EBV latent membrane protein 1 (LMP1) promotes MDSC expansion in the tumor microenvironment by promoting extra-mitochondrial glycolysis in malignant cells, which is a scenario for immune escape initially suggested by the frequent, concomitant detection of abundant LMP1, glucose transporter 1 (GLUT1) and CD33+ MDSCs in tumor sections...
July 21, 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28732077/mutations-in-the-caenorhabditis-elegans-orthologs-of-human-genes-required-for-mitochondrial-trna-modification-cause-similar-electron-transport-chain-defects-but-different-nuclear-responses
#7
Carmen Navarro-González, Ismaïl Moukadiri, Magda Villarroya, Ernesto López-Pascual, Simon Tuck, M-Eugenia Armengod
Several oxidative phosphorylation (OXPHOS) diseases are caused by defects in the post-transcriptional modification of mitochondrial tRNAs (mt-tRNAs). Mutations in MTO1 or GTPBP3 impair the modification of the wobble uridine at position 5 of the pyrimidine ring and cause heart failure. Mutations in TRMU affect modification at position 2 and cause liver disease. Presently, the molecular basis of the diseases and why mutations in the different genes lead to such different clinical symptoms is poorly understood...
July 21, 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28732061/melatonin-pre-treatment-mitigates-shsy-5y-cells-against-oxaliplatin-induced-mitochondrial-stress-and-apoptotic-cell-death
#8
Mohammad Waseem, Upasana Sahu, Mohd Salman, Arnab Choudhury, Sudeshna Kar, Heena Tabassum, Suhel Parvez
Oxaliplatin (Oxa) treatment to SH-SY5Y human neuroblastoma cells has been shown by previous studies to induce oxidative stress, which in turn modulates intracellular signaling cascades resulting in cell death. While this phenomenon of Oxa-induced neurotoxicity is known, the underlying mechanisms involved in this cell death cascade must be clarified. Moreover, there is still little known regarding the roles of neuronal mitochondria and cytosolic compartments in mediating Oxa-induced neurotoxicity. With a better grasp of the mechanisms driving neurotoxicity in Oxa-treated SH-SY5Y cells, we can then identify certain pathways to target in protecting against neurotoxic cell damage...
2017: PloS One
https://www.readbyqxmd.com/read/28731850/the-diagnostic-accuracy-of-biomarkers-for-diagnosis-of-primary-biliary-cholangitis-pbc-in-anti-mitochondrial-antibody-ama-negative-pbc-patients-a-review-of-literature
#9
Federica de Liso, Caterina Matinato, Mariangela Ronchi, Rita Maiavacca
Primary biliary cholangitis (PBC), also known as primary biliary cirrhosis, is an autoimmune disease of the liver characterized by anti-mitochondrial antibodies (AMA) in 90%-95% of patients. The aim of this study was to evaluate the diagnostic value of several serum biomarkers in patients with PBC but negative for AMA. Some antinuclear antibodies (ANA) pattern, detected by indirect immunofluorescence (IIF), such as multiple nuclear dot (MND) and rim-like patterns are well-known to be specific for PBC. The corresponding nuclear antigens are the components of the nuclear pore complex (Gp210 for rim-like pattern) and Sp100, PML proteins (for MND pattern) detectable by immunoblotting and ELISA methods...
July 21, 2017: Clinical Chemistry and Laboratory Medicine: CCLM
https://www.readbyqxmd.com/read/28731433/the-effects-of-cardiotrophin-1-on-early-synaptic-mitochondrial-dysfunction-and-synaptic-pathology-in-appswe-ps1de9-mice
#10
Dongmei Wang, Xiaozhuan Liu, Yumei Liu, Sanqiang Li, Chenying Wang
The coexistence of neuronal mitochondrial pathology and synaptic dysfunction is an early pathological feature of Alzheimer's disease (AD). Cardiotrophin-1 (CT-1) has been shown to exhibit impressive neuroprotective effects. Previous studies have shown positive effects of CT-1 on brain glucose metabolism and cognition in APPswe/PS1dE9 transgenic mice; however, little is known about the effects of CT-1 on early synaptic mitochondrial dysfunction and resultant synaptic pathology in the brain. In this study, 4-month-old transgenic mice with brain tissue-specific CT-1 expression were used alone or in combination with APPswe/PS1dE9 transgenic mice to evaluate the effect of CT-1 on synaptic mitochondrial dysfunction and resultant synaptic pathology, and cryptic memory deficits in the APPswe/PS1dE9 transgenic mice...
July 19, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28731233/integration-of-cellular-and-molecular-endpoints-to-assess-the-toxicity-of-polycyclic-aromatic-hydrocarbons-in-hepg2-cell-line
#11
Patrícia I Morgado, Sílvia Jose, Riccardo Wanke, Alexandra M M Antunes, Ana Sofia Cardoso, Luisa Jordao
Polycyclic aromatic hydrocarbons (PAHs) are persistent pollutants present in the environment with known mutagenic and carcinogenic properties. In the present study the effect of exposure to single or multiple doses of benzo[a]anthracene (BaA), pyrene (Pyr) and three halogenated derivatives of these compounds (1-ClPyr; 1-BrPyr and 7-ClBaA) were evaluated in a liver-derived human cell line (HepG2). Cytotoxicity as assessed by the classic MTT and neutral red assays showed a mild toxic effect in response to single or multiple dose exposure for up to 72h; except for multiple dose exposure to BaA and 7-ClBaA (1μM per day during 4 days) and single exposure to 10 μM BaA...
July 21, 2017: Environmental Toxicology and Chemistry
https://www.readbyqxmd.com/read/28731223/neferine-modulates-igf-1r-nrf2-signaling-in-doxorubicin-treated-h9c2-cardiomyoblasts
#12
Lohanathan Bharathi Priya, Rathinasamy Baskaran, Chih-Yang Huang, Viswanadha Vijaya Padma
Doxorubicin (DOX) induced cardiotoxicity is a major problem during chemotherapy of cancers. DOX-mediated suppression of type 1 IGF receptor (IGF-1R) signaling leads to cardiac dysfunction. Neferine, a bisbezylisoquinoline alkaloid from the seed embryos of Nelumbo nucifera Gaertn possesses a distinct range of pharmacological properties. Herewith, the present study attempts to elucidate the protective role of neferine against DOX induced toxicity in H9c2 rat cardiomyoblast cell line model. DOX-treated H9c2 cells significantly increased mitochondrial superoxide generation, depleted cellular antioxidant status, suppressed the activation of IGF-1R signaling via PI3K/Akt/mTOR and induced autophagy by the activation of ULK1, Beclin1, Atg7 and LC3B...
July 21, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28731195/inhibition-of-arc-promoting-the-apoptosis-of-rat-pulmonary-arterial-smooth-muscle-cells-after-serum-deprivation-in%C3%A2-vitro
#13
Jie Zhang, Zeyu Wu, Ming Guan, Hongyan Lu, Xuming Mo
Apoptosis has important pathophysiological consequences contributing to pulmonary arterial hypertension (PAH). However, the mechanism underlying apoptosis in PAH remains unknown. Apoptosis repressor with caspase recruitment domain (ARC) is an essential factor in cell apoptosis, and regulates intrinsic and extrinsic apoptosis signaling pathways. It is hypothesized that ARC may be involved in the apoptotic responses of pulmonary arterial smooth muscle cells (PASMCs) following mild chronic injury. In the present study, serum deprivation (SD) was used to induce apoptosis of PASMCs...
July 21, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28731183/paeoniflorin-exerts-neuroprotective-effects-against-glutamate%C3%A2-induced-pc12-cellular-cytotoxicity-by-inhibiting-apoptosis
#14
Ahong Chen, Hongyun Wang, Yuqin Zhang, Xiaoying Wang, Lishuang Yu, Wen Xu, Wei Xu, Yu Lin
Paeoniflorin (PF) is an active ingredient of Radix Paeoniae, which is known to exert neuroprotective effects. However, the mechanims behind the neuroprotective effects of PF are not yet fully understood. The apoptosis of neurons plays an important role in the cerebral ischemia-induced cascade response. This study aimed to investigate neuroprotective effects of PF against glutamate‑induced PC12 cellular cytotoxicity and to determine whether these effects are mediated via the inhibition of apoptosis in vitro and the activity of mitochondrial apoptosis-associated proteins in PC12 cells...
July 20, 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/28731097/dba-induced-caspase-3-dependent-apoptosis-occurs-through-mitochondrial-translocation-of-cyt-c-in-the-rat-hippocampus
#15
Wenbo Jiang, Yingying Chen, Bai Li, Shuying Gao
Dibromoacetic acid (DBA), a by-product of disinfection, develops in drinking water during chlorination or ozonation processes. Water intake is the main source of DBA exposure in humans, which is potentially neurotoxic. The present study investigated the neurotoxic effects of DBA by assessing the behavioral and biochemical characteristics of Sprague Dawley rats intragastrically treated with DBA at concentrations of 20, 50 and 125 mg kg(-1) body weight for 28 consecutive days. The results indicated that animal weight gain and food consumption were not significantly affected by DBA...
July 21, 2017: Molecular BioSystems
https://www.readbyqxmd.com/read/28730962/phosphonium-salt-displays-cytotoxic-effects-against-human-cancer-cell-lines
#16
Dhanyalayam Dhanya, Giuseppe Palma, AnnaRita Cappello, Annaluisa Mariconda, Maria Stefania Sinicropi, Francesca Giordano, Vitale Del Vecchio, Anna Ramunno, Claudio Arra, Pasquale Longo, Carmela Saturnino
Aims/ Objective: Phosphonium salts are compounds whose structural characteristics enable them to cross the plasma and mitochondrial membrane with ease. Cancer cells have higher plasma membrane potentials than normal cells, phosphonium salts selectively accumulate in the mitochondria of neoplastic cells and inhibit mitochondrial function. METHOD: In the presente work, we investigate the cytotoxic activity of lipophilic phosphonium salt (11-methoxy11-oxo-undecyl) triphenylphosphonium bromide (MUTP) as well as of two new phosphine oxide salts, 3,3'-(methylphosphoryl) dibenzenaminium chloride (SBAMPO) and 3,3' (phenylphosphoryl) dibenzenaminium chloride (SBAPPO) on the proliferation of breast cancer cell line (MCF-7) and human uterin cervix adenocarcinoma cells (HeLa)...
July 19, 2017: Anti-cancer Agents in Medicinal Chemistry
https://www.readbyqxmd.com/read/28730954/evaluation-of-in-vitro-anti-psoriatic-activity-of-a-novel-polyherbal-formulation-by-multiparametric-analysis
#17
Nadav Shraibom, Alka Madaan, Vidushi Joshi, Ritu Verma, Anika Chaudhary, Gautam Mishra, Anshumali Awasthi, Anu Taneja Singh, Manu Jaggi
The beneficial role of traditional herbal medicines in the treatment of inflammatory skin disorders has been widely reported. Psoriasis is characterized by uncontrolled hyper-proliferation of keratinocytes, disturbed apoptosis, over-secretion of inflammatory cytokines and angiogenic factors. We have developed a novel aqueous polyherbal formulation (SIRB-001) consisting of 3 herbs; Rheum palmatum L., Rehmannia glutinosa Libosch and Lonicera Japonica in the ratio 1:1:3. SIRB-001 has demonstrated efficacious effects in psoriasis patients...
July 20, 2017: Anti-inflammatory & Anti-allergy Agents in Medicinal Chemistry
https://www.readbyqxmd.com/read/28730835/the-effect-of-very-low-calorie-diet-on-mitochondrial-dysfunction-in-subcutaneous-adipose-tissue-and-peripheral-monocytes-of-obese-subjects-with-type-2-diabetes-mellitus
#18
M Urbanová, M Mráz, V Ďurovcová, P Trachta, J Kloučková, P Kaválková, D Haluzíková, Z Lacinová, H Hansíková, L Wenchich, M Kršek, M Haluzík
Mitochondrial dysfunction is a potentially important player in the development of insulin resistance and type 2 diabetes mellitus (T2DM). We investigated the changes of mRNA expression of genes encoding main enzymatic complexes of mitochondrial respiratory chain in subcutaneous adipose tissue (SCAT) and peripheral monocytes (PM) of 11 subjects with simple obesity (OB), 16 obese patients with T2DM and 17 healthy lean subjects (C) before and after very low-calorie diet (VLCD) using quantitative real time PCR...
July 18, 2017: Physiological Research
https://www.readbyqxmd.com/read/28730764/mtor-deregulation-in-oral-cavity-squamous-cell-carcinoma
#19
Nicholas S Mastronikolis, Evangelos Tsiambas, Theodoros A Papadas, Panagiotis P Fotiades, Athanasios T Papadas, Stylianos N Mastronikolis, Ioannis Kastanioudakis, Vasileios Ragos
Signal transduction pathways consist of a variety of inter- and intra-cellular molecules. They act as supporting mechanisms for cell survival and homeostasis. Among them, the phosphatidylinositol 3-kinase (PI3K)/tumor suppressor phosphatase and tensin homologue deleted on chromosome ten (PTEN)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR) pathway plays a crucial role in regulating normal cell growth based on growth factor receptors (GFRs) interaction, including epidermal GFR (type II-HER2) and insulin GFR (IGF)...
May 2017: Journal of B.U.ON.: Official Journal of the Balkan Union of Oncology
https://www.readbyqxmd.com/read/28730739/effect-of-the-age-of-broodstock-males-on-sperm-function-during-cold-storage-in-the-trout-oncorhynchus-mykiss
#20
J Risopatrón, O Merino, C Cheuquemán, E Figueroa, R Sánchez, J G Farías, I Valdebenito
The knowledge of sperm quality in the broodstock males of different ages is a prerequisite to identify the reproductive ability of cultivated fish for the hatchery management. Thus, in this work, we analysed sperm function of the semen stored of broodstock males of rainbow trout (Oncorhychus mykiss) in different reproductive ages (2, 3 and 4 years old). Sperm samples of each reproductive age were stored in Storfish(®) during 10 days at 4°C, and then, motility, viability, mitochondrial function (MMP), superoxide anion (O2-) level and DNA fragmentation (DNAfrag ) were assessed...
July 21, 2017: Andrologia
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