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https://www.readbyqxmd.com/read/28345620/acute-and-chronic-mitochondrial-respiratory-chain-deficiency-differentially-regulate-lysosomal-biogenesis
#1
Lorena Fernández-Mosquera, Cátia V Diogo, King Faisal Yambire, Gabriela L Santos, Marta Luna Sánchez, Paule Bénit, Pierre Rustin, Luis Carlos Lopez, Ira Milosevic, Nuno Raimundo
Mitochondria are key cellular signaling platforms, affecting fundamental processes such as cell proliferation, differentiation and death. However, it remains unclear how mitochondrial signaling affects other organelles, particularly lysosomes. Here, we demonstrate that mitochondrial respiratory chain (RC) impairments elicit a stress signaling pathway that regulates lysosomal biogenesis via the microphtalmia transcription factor family. Interestingly, the effect of mitochondrial stress over lysosomal biogenesis depends on the timeframe of the stress elicited: while RC inhibition with rotenone or uncoupling with CCCP initially triggers lysosomal biogenesis, the effect peaks after few hours and returns to baseline...
March 27, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28343085/guava-fruit-extract-and-its-triterpene-constituents-have-osteoanabolic-effect-stimulation-of-osteoblast-differentiation-by-activation-of-mitochondrial-respiration-via-the-wnt-%C3%AE-catenin-signaling
#2
Konica Porwal, Subhashis Pal, Kapil Dev, Shyamsundar Pal China, Yogesh Kumar, Chandan Singh, Tarun Barbhuyan, Neeraj Sinha, Sabyasachi Sanyal, Arun Kumar Trivedi, Rakesh Maurya, Naibedya Chattopadhyay
The aim of this study was to evaluate the skeletal effect of guava triterpene-enriched extract (GE) in rats and identify osteogenic compounds thereof, and determine their modes of action. In growing female rats, GE at 250 mg/kg dose increased parameters of peak bone mass including femur length, bone mineral density (BMD) and biomechanical strength, suggesting that GE promoted modeling-directed bone growth. GE also stimulated bone regeneration at the site of bone injury. In adult osteopenic rats (osteopenia induced by ovariectomy, OVX) GE completely restored the lost bones at both axial and appendicular sites, suggesting a strong osteoanabolic effect...
March 8, 2017: Journal of Nutritional Biochemistry
https://www.readbyqxmd.com/read/28338413/human-tissue-engineered-skeletal-muscle-myobundles-to-measure-oxygen-uptake-and-assess-mitochondrial-toxicity
#3
Brittany N J Davis, Jeffrey W Santoso, Michaela J Walker, Cindy S Cheng, Timothy R Koves, William E Kraus, George A Truskey
Mitochondrial dysfunction is responsible for the toxicity of a number of drugs. Current isolated mitochondria or cellular monoculture mitochondrial respiration measurement systems lack physiological relevance. Using a tissue engineering rather than cell- or mitochondria-based approach enables a more physiologically relevant detection of drug-induced mitochondrial impairment. To probe oxygen consumption and mitochondrial health, we assayed the bioenergetic profile of engineered three-dimensional human skeletal muscle myobundles derived from primary myoblasts...
March 24, 2017: Tissue Engineering. Part C, Methods
https://www.readbyqxmd.com/read/28332229/type-i-interferons-in-parkinson-s-disease-innate-inflammatory-response-drives-fate-of-neurons-in-model-of-degenerative-brain-disorder-an-editorial-comment-on-type-i-interferons-mediate-the-neuroinflammatory-response-and-neurotoxicity-induced-by-rotenone
#4
EDITORIAL
Katja M Kanninen, Anthony R White
Read the commented article 'Type-I interferons mediate the neuroinflammatory response and neurotoxicity induced by rotenone' on page 75.
April 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/28301304/neuroprotective-and-therapeutic-effect-of-caffeine-on-the-rat-model-of-parkinson-s-disease-induced-by-rotenone
#5
Yasser A Khadrawy, Ahmed M Salem, Karima A El-Shamy, Emad K Ahmed, Nevein N Fadl, Eman N Hosny
The present study aimed to investigate the protective and therapeutic effects of caffeine on rotenone-induced rat model of Parkinson's disease (PD). Rats were divided into control, PD model induced by rotenone (1.5 mg/kg intraperitoneally (i.p.) for 45 days), protected group injected with caffeine (30 mg/kg, i.p.) and rotenone for 45 days (during the development of PD model), and treated group injected with caffeine (30 mg/kg, i.p.) for 45 days after induction of PD model. The data revealed a state of oxidative and nitrosative stress in the midbrain and the striatum of animal model of PD as indicated from the increased lipid peroxidation and nitric oxide levels and the decreased reduced glutathione level and activities of glutathione-S-transferase and superoxide dismutase...
September 3, 2017: Journal of Dietary Supplements
https://www.readbyqxmd.com/read/28300150/s-nitrosylation-of-uchl1-induces-its-structural-instability-and-promotes-%C3%AE-synuclein-aggregation
#6
Roshan Kumar, Deepak K Jangir, Garima Verma, Shashi Shekhar, Pranita Hanpude, Sanjay Kumar, Raniki Kumari, Nirpendra Singh, Neel Sarovar Bhavesh, Nihar Ranjan Jana, Tushar Kanti Maiti
Ubiquitin C-terminal Hydrolase-1 (UCHL1) is a deubiquitinating enzyme, which plays a key role in Parkinson's disease (PD). It is one of the most important proteins, which constitute Lewy body in PD patient. However, how this well folded highly soluble protein presents in this proteinaceous aggregate is still unclear. We report here that UCHL1 undergoes S-nitrosylation in vitro and rotenone induced PD mouse model. The preferential nitrosylation in the Cys 90, Cys 152 and Cys 220 has been observed which alters the catalytic activity and structural stability...
March 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28298333/multiple-ampk-activators-inhibit-l-carnitine-uptake-in-c2c12-skeletal-muscle-myotubes
#7
Andy Shaw, Stewart Jeromson, Kenneth R Watterson, John D Pediani, Iain Gallagher, Tim Whalley, Gillian Dreczkowski, Naomi Brooks, Stuart Galloway, D Lee Hamilton
Mutations in the gene that encodes the principal L-Carnitine transporter, OCTN2, can lead to a reduced intracellular L-Carnitine pool and the disease Primary Carnitine Deficiency. L-Carnitine supplementation is used therapeutically to increase intracellular L-Carnitine. As AMPK and insulin regulate fat metabolism and substrate uptake we hypothesised that AMPK activating compounds and insulin would increase L-Carnitine uptake in C2C12 myotubes. The cells express all three OCTN transporters at the mRNA level and immunohistochemistry confirmed expression at the protein level...
March 15, 2017: American Journal of Physiology. Cell Physiology
https://www.readbyqxmd.com/read/28286206/simplified-qpcr-method-for-detecting-excessive-mtdna-damage-induced-by-exogenous-factors
#8
Artem P Gureev, Ekaterina A Shaforostova, Anatoly A Starkov, Vasily N Popov
Damage to mitochondrial DNA (mtDNA) is a meaningful biomarker for evaluating genotoxicity of drugs and environmental toxins. Existing PCR methods utilize long mtDNA fragments (∼8-10kb), which complicates detecting exact sites of mtDNA damage. To identify the mtDNA regions most susceptible to damage, we have developed and validated a set of primers to amplify ∼2kb long fragments, while covering over 95% of mouse mtDNA. We have modified the detection method by greatly increasing the enrichment of mtDNA, which allows us solving the problem of non-specific primer annealing to nuclear DNA...
March 9, 2017: Toxicology
https://www.readbyqxmd.com/read/28283350/ultrafine-carbon-particles-promote-rotenone-induced-dopamine-neuronal-loss-through-activating-microglial-nadph-oxidase
#9
Yinxi Wang, Dan Liu, Huifeng Zhang, Yixin Wang, Ling Wei, Yutong Liu, Jieying Liao, Hui-Ming Gao, Hui Zhou
BACKGROUND: Atmospheric ultrafine particles (UFPs) and pesticide rotenone were considered as potential environmental risk factors for Parkinson's disease (PD). However, whether and how UFPs alone and in combination with rotenone affect the pathogenesis of PD remains largely unknown. METHODS: Ultrafine carbon black (ufCB, a surrogate of UFPs) and rotenone were used individually or in combination to determine their roles in chronic dopaminergic (DA) loss in neuron-glia, and neuron-enriched, mix-glia cultures...
March 7, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28281393/altered-expression-of-a-metformin-mediated-radiation-response-in-sa-nh-and-fsa-tumor-cells-treated-under-in-vitro-and-in-vivo-growth-conditions
#10
Jeffrey S Murley, Richard C Miller, Raziye Rana Senlik, Alfred W Rademaker, David J Grdina
PURPOSE: To assess the radio-sensitizing effect of the biguanide drug Metformin used alone or in combination with reactive oxygen species (ROS) modifying agents N-acetyl-L-cysteine (NAC) or emodin, and contrasted to the mitochondrial complex 1 inhibitor rotenone in altering the radiation responses of the p53 wild type SA-NH and p53 mutant FSa mouse tumor lines grown either in vitro or in vivo. MATERIALS AND METHODS: Tumor cells were grown to confluence in vitro and exposed to a single 4 Gy dose in the presence or absence of Metformin (5 mM) and ROS modifiers or to 10 Gy with or without Metformin as tumors in the flanks of C3H mice using a tumor growth delay assay...
March 10, 2017: International Journal of Radiation Biology
https://www.readbyqxmd.com/read/28279750/neurons-and-astrocytes-in-an-infantile-neuroaxonal-dystrophy-inad-mouse-model-show-characteristic-alterations-in-glutamate-induced-ca-2-signaling
#11
Mikhail Strokin, Georg Reiser
INAD (infantile neuroaxonal dystrophy, OMIM#256600), an autosomal recessive inherited degenerative disease, is associated with PLA2G6 mutations. PLA2G6 encodes Ca(2+)-independent phospholipase A2 (VIA iPLA2). However, it is unclear how the PLA2G6-mutations lead to disease. Non-canonical functions, which were suggested for VIA iPLA2, such as regulation of cellular and mitochondrial Ca(2+) are promising candidates. Therefore, we investigate glutamate (Glu)-evoked Ca(2+) signals in neurons and astrocytes in co-culture obtained from three INAD mouse model strains with Pla2g6 mutations, (i) hypomorphic Pla2g6 allele with reduced transcript levels, (ii) knocked-out Pla2g6, and (iii) (G373R)-point mutation with inactive VIA iPLA2 enzyme...
March 6, 2017: Neurochemistry International
https://www.readbyqxmd.com/read/28276272/gut-brain-and-brain-gut-axis-in-parkinson-s-disease-models-effects-of-a-uridine-and-fish-oil-diet
#12
Paula Perez-Pardo, Hemraj B Dodiya, Laus M Broersen, Hidde Douna, Nick van Wijk, Sofia Lopes da Silva, Johan Garssen, Ali Keshavarzian, Aletta D Kraneveld
Recent investigations have focused on the potential role of gastrointestinal (GI) abnormalities in the pathogenesis of Parkinson's disease (PD). The 'dual-hit' hypothesis of PD speculates that a putative pathogen enters the brain via two routes: the olfactory system and the GI system. Here, we investigated (1) whether local exposures of the neurotoxin rotenone in the gut or the brain of mice could induce PD-like neurological and GI phenotypes as well as a characteristic neuropathology in accordance with this 'dual-hit hypothesis' and (2) the effects of a diet containing uridine and fish oil providing docosahexaenoic acid (DHA), in both models...
March 9, 2017: Nutritional Neuroscience
https://www.readbyqxmd.com/read/28276259/effects-of-eldepryl-on-glial-cell-proliferation-and-activation-in-the-substantia-nigra-and-striatum-in-a-rat-model-of-parkinson-s-disease
#13
Bin Liu, Chaonan Lv, Jinxia Zhang, Ying Liu, Jing Sun, Xiaohua Cheng, Wenjing Mao, Yuanyuan Ma, Shiying Li
OBJECTIVES: Inflammation is involved in the occurrence and progression of Parkinson's disease (PD), but the exact mechanisms remain unclear. This study aimed to observe the expressions of glial fibrillary acidic protein (GFAP) and integrin αM (CD11b) in the substantia nigra and striatum, and to investigate the effect of eldepryl on these expressions in a rat model of PD. METHODS: Seventy-two rats were randomly divided into three groups: control, model, and eldepryl...
March 9, 2017: Neurological Research
https://www.readbyqxmd.com/read/28259991/the-involvement-of-eag1-potassium-channels-and-mir-34a-in-rotenone-induced-death-of-dopaminergic-sh-sy5y-cells
#14
Camila Hillesheim Horst, Ricardo Titze-de-Almeida, Simoneide Souza Titze-de-Almeida
The loss of dopaminergic neurons and the resultant motor impairment are hallmarks of Parkinson's disease. The SH‑SY5Y cell line is a model of dopaminergic neurons, and allows for the study of dopaminergic neuronal injury. Previous studies have revealed changes in Ether à go‑go 1 (Eag1) potassium channel expression during p53-induced SH‑SY5Y apoptosis, and the regulatory involvement of microRNA‑34a (miR‑34a) was demonstrated. In the present study, the involvement of Eag1 and miR‑34a in rotenone‑induced SH‑SY5Y cell injury was investigated...
April 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28258522/sitagliptin-and-liraglutide-reversed-nigrostriatal-degeneration-of-rodent-brain-in-rotenone-induced-parkinson-s-disease
#15
Ghada A Badawi, Mai A Abd El Fattah, Hala F Zaki, Moushira I El Sayed
The present study investigated the possible relationship between pro-inflammatory cytokines and programmed nigral neuronal death in rotenone model of Parkinson's disease (PD). Sitagliptin and liraglutide efficacy to inhibit the inflammatory-apoptotic degenerative process were investigated, too. The experimental PD were induced in male albino rats by ten subcutaneously injections of rotenone (3 mg/kg/day, s.c). All treatment drugs were administered for 16 days after induction of Parkinson rat's model. Sitagliptin and liraglutide were administered in three different dose levels (10-20-30 mg/kg, p...
March 4, 2017: Inflammopharmacology
https://www.readbyqxmd.com/read/28254432/mitochondrial-ccar2-dbc1-is-required-for-cell-survival-against-rotenone-induced-mitochondrial-stress
#16
Wootae Kim, Min Gyeong Cheon, Ja-Eun Kim
CCAR2 (cell cycle and apoptosis regulator protein 2; formerly DBC1, deleted in breast cancer 1) functions in diverse cellular processes including responses to genotoxic and metabolic stresses. However, its role in the mitochondrial stress response has not been fully elucidated. To investigate how CCAR2 regulates stress response, we purified CCAR2-containing complexes. Interestingly, the results revealed that CCAR2 localized to the mitochondria, and also bound Hsp60 (heat shock protein 60), a mitochondrial chaperone...
April 15, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28254005/cyclodextrin-based-miniaturized-solid-phase-extraction-for-biopesticides-analysis-in-water-and-vegetable-juices-samples-analyzed-by-ultra-high-performance-liquid-chromatography-coupled-with-quadrupole-time-of-flight-mass-spectrometry
#17
Li-Qing Peng, Li-Hong Ye, Jun Cao, Yan-Xu Chang, Qin Li, Mingrui An, Zhijing Tan, Jing-Jing Xu
A cyclodextrin-based miniaturized solid-phase extraction was developed to extract biopesticides from water and vegetable juices. The analytes were detected by ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry. In the solid-phase extraction (SPE) procedure, the liquid sample solution is passed through a packed column filled with 40mg of HP-β-CD, and then the target analytes are absorbed and finally eluted with methanol-acetic acid (90:10, v/v) into a collection tube...
July 1, 2017: Food Chemistry
https://www.readbyqxmd.com/read/28249117/anti-inflammatory-and-neuroprotective-activity-of-boswellic-acids-in-rotenone-parkinsonian-rats
#18
Angie Ameen, Amany Elkazaz, Hala M F A Mohammad, Bassant Mohamed Barakat
There is evidence that inflammation and oxidative stress contribute to neurodegenerative changes observed in Parkinson's disease (PD). Unfortunately, there is a lack of curative treatments for this debilitating movement disorder. Boswellic acids (BAs) are pentacyclic triterpene molecules of plant origin and have been utilized for treating many inflammatory conditions. The current study was conducted to explore the role of BAs in protection from rotenone-induced experimental Parkinsonism. Twenty four rats were assigned as vehicle group, rotenone control group: rats received rotenone (1 mg/kg) every 48...
March 1, 2017: Canadian Journal of Physiology and Pharmacology
https://www.readbyqxmd.com/read/28247212/pyruvate-antioxidant-roles-in-human-fibroblasts-and-embryonic-stem-cells
#19
Priscila Ramos-Ibeas, Maria Barandalla, Silvia Colleoni, Giovanna Lazzari
Oxidative stress has been related to multiple diseases, especially during early embryonic development, when environmental alterations can lead to long-term deleterious effects. In vitro studies of oxidative stress have been mainly focused on somatic cells, but embryonic stem cells (ESCs) represent a promising model of early embryonic development as they are the in vitro equivalent to pluripotent cells in the embryo. Human fibroblasts and ESCs were exposed to different pro-oxidant agents (hydrogen peroxide, tert-butyl hydroperoxide (TBHP), and rotenone) and antioxidants (sodium pyruvate, N-acetylcysteine, Trolox, and sodium selenite) during a 72 h oxidative stress treatment...
February 28, 2017: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/28245986/dj-1-regulating-pi3k-nrf2-signaling-plays-a-significant-role-in-bibenzyl-compound-20c-mediated-neuroprotection-against-rotenone-induced-oxidative-insult
#20
Xiao-Ling Zhang, Yu-He Yuan, Qian-Hang Shao, Zhen-Zhen Wang, Cheng-Gen Zhu, Jian-Gong Shi, Kai-Li Ma, Xu Yan, Nai-Hong Chen
Oxidative stress is thought to be involved in the development of Parkinson's disease (PD). We previously reported that 20C, a bibenzyl compound isolated from Gastrodia elata, possesses antioxidative properties, but its in-depth molecular mechanisms against rotenone-induced neurotoxicity remains unknown. Recent studies indicate that without intact DJ-1, nuclear factor erythroid 2-related factor (Nrf2) protein becomes unstable, and the activity of Nrf2-mediated downstream antioxidant enzymes are thereby suppressed...
April 5, 2017: Toxicology Letters
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