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https://www.readbyqxmd.com/read/28100784/mitochondrial-o-glcnac-transferase-mogt-regulates-mitochondrial-structure-function-and-survival-in-hela-cells
#1
Juliana L Sacoman, Raul Y Dagda, Amanda R Burnham-Marusich, Ruben K Dagda, Patricia M Berninsone
O-linked N-acetylglucosamine transferase (OGT) catalyzes O-GlcNAcylation of target proteins and regulates numerous biological processes. OGT is encoded by a single gene that yields nucleocytosolic and mitochondrial isoforms. To date, the role of the mitochondrial isoform of OGT (mOGT) remains largely unknown. Using high-throughput proteomics, we identified 84 candidate mitochondrial glycoproteins, of which 44 are novel. Notably, two of the candidate glycoproteins identified (cytochrome oxidase 2 (COX2) and NADH: ubiquinone oxidoreductase core subunit 4 (MT-ND4)) are encoded by mitochondrial DNA...
January 18, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28098219/combined-lrrk2-mutation-aging-and-chronic-low-dose-oral-rotenone-as-a-model-of-parkinson-s-disease
#2
Hui-Fang Liu, Philip Wing-Lok Ho, Gideon Chi-Ting Leung, Colin Siu-Chi Lam, Shirley Yin-Yu Pang, Lingfei Li, Michelle Hiu-Wai Kung, David Boyer Ramsden, Shu-Leong Ho
Aging, genetics and environmental toxicity are important etiological factors in Parkinson's disease (PD). However, its pathogenesis remains unclear. A major obstacle is the lack of an appropriate experimental model which incorporates genetic susceptibility, aging and prolonged environmental toxicity. Here, we explored the interplay amongst these factors using mutant LRRK2(R1441G) (leucine-rich-repeat-kinase-2) knockin mice. We found that mutant primary cortical and mesencephalic dopaminergic neurons were more susceptible to rotenone-induced ATP deficiency and cell death...
January 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28097465/hydroxysafflor-yellow-a-improves-motor-dysfunction-in-the-rotenone-induced-mice-model-of-parkinson-s-disease
#3
Tian Wang, Lijie Wang, Cuiting Li, Bing Han, Zhenhua Wang, Ji Li, Yan Lv, Shuyun Wang, Fenghua Fu
Dopamine D3 receptor (DRD3) is diminished in patients of Parkinson's disease (PD). Brain-derived neurotrophic factor (BDNF) is responsible for regulating expression of the DRD3 in the brain. Our previous study showed that hydroxysafflor yellow A (HSYA) could increase BDNF content in the striatum of PD mice. This experiment aimed to evaluate whether HSYA can improve the motor dysfunction induced by rotenone through regulating the BDNF/TrkB/DRD3 signaling pathway in mice. Male C57/BL6 mice were intraperitoneally treated with HSYA...
January 17, 2017: Neurochemical Research
https://www.readbyqxmd.com/read/28096185/transcriptomic-profiling-of-purified-patient-derived-dopamine-neurons-identifies-convergent-perturbations-and-therapeutics-for-parkinson-s-disease
#4
Cynthia Sandor, Paul Robertson, Charmaine Lang, Andreas Heger, Heather Booth, Jane Vowles, Lorna Witty, Rory Bowden, Michele Hu, Sally A Cowley, Richard Wade-Martins, Caleb Webber
While induced pluripotent stem cell (iPSC) technologies enable the study of inaccessible patient cell types, cellular heterogeneity can confound the comparison of gene expression profiles between iPSC-derived cell lines. Here, we purified iPSC-derived human dopaminergic neurons (DaNs) using the intracellular marker, tyrosine hydroxylase. Once purified, the transcriptomic profiles of iPSC-derived DaNs appear remarkably similar to profiles obtained from mature post-mortem DaNs. Comparison of the profiles of purified iPSC-derived DaNs derived from Parkinson's disease (PD) patients carrying LRRK2 G2019S variants to controls identified significant functional convergence amongst differentially-expressed (DE) genes...
January 17, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28088644/tert-butyl-hydroperoxide-t-bhp-induced-apoptosis-and-necroptosis-in-endothelial-cells-roles-of-nox4-and-mitochondrion
#5
Wenwen Zhao, Haitao Feng, Wen Sun, Kang Liu, Jin-Jian Lu, Xiuping Chen
Oxidative stress causes endothelial death while underlying mechanisms remain elusive. Herein, the pro-death effect of tert-butyl hydroperoxide (t-BHP) was investigated with low concentration (50μM) of t-BHP (t-BHPL) and high concentration (500μM) of t-BHP (t-BHPH). Both t-BHPL and t-BHPH induced endothelial cell death was determined. T-BHPL induced caspase-dependent apoptosis and reactive oxygen species (ROS) generation, which was inhibited by N-acetyl-L-cysteine (NAC). Furthermore, NADPH oxidase inhibitor diphenyleneiodonium (DPI), NOX4 siRNA, and NOX4 inhibitor GKT137831 reduced t-BHPL-induced ROS generation while mitochondrial respiratory chain inhibitors rotenone (Rot), 2-thenoyltrifluoroacetone (TTFA), and antimycin A (AA) failed to do so...
January 5, 2017: Redox Biology
https://www.readbyqxmd.com/read/28088492/pikuni-blackfeet-traditional-medicine-neuroprotective-activities-of-medicinal-plants-used-to-treat-parkinson-s-disease-related-symptoms
#6
Aurélie de Rus Jacquet, Mitali Arun Tambe, Sin Ying Ma, George P McCabe, Jay Hansford C Vest, Jean-Christophe Rochet
ETHNOPHARMACOLOGICAL RELEVANCE: Parkinson's disease (PD) is a multifactorial neurodegenerative disorder affecting 5% of the population over the age of 85 years. Current treatments primarily involve dopamine replacement therapy, which leads to temporary relief of motor symptoms but fails to slow the underlying neurodegeneration. Thus, there is a need for safe PD therapies with neuroprotective activity. In this study, we analyzed contemporary herbal medicinal practices used by members of the Pikuni-Blackfeet tribe from Western Montana to treat PD-related symptoms, in an effort to identify medicinal plants that are affordable to traditional communities and accessible to larger populations...
January 11, 2017: Journal of Ethnopharmacology
https://www.readbyqxmd.com/read/28067625/pituitary-adenylate-cyclase-activating-polypeptide-pacap-has-neuroprotective-function-in-dopamine-based-neurodegeneration-developed-in-two-parkinsonian-models
#7
G Maasz, Z Zrinyi, D Reglodi, D Petrovics, A Rivnyak, T Kiss, A Jungling, A Tamas, Z Pirger
It has been observed that pituitary-adenylate cyclase activating polypeptide (PACAP) rescued DAergic neurons from neurodegeneration and improved motor alterations induced by 6-hydroxy-dopamine (6-OHDA) in rat parkinsonian models. Recently we investigated the molecular background of the neuroprotective effect of PACAP in DA-based neurodegeneration using rotenone-induced snail and 6-OHDA-induced rat models of Parkinson's disease. The behavioural activity, monoamine (DA and serotonin), metabolic enzyme (S-COMT, MB-COMT and MAO-B) and PARK7/DJ-1 protein contents were measured before and after PACAP-treatment in both models...
December 22, 2016: Disease Models & Mechanisms
https://www.readbyqxmd.com/read/28055011/neuronal-hemoglobin-affects-dopaminergic-cells-response-to-stress
#8
Marta Codrich, Maria Bertuzzi, Roberta Russo, Margherita Francescatto, Stefano Espinoza, Lorena Zentilin, Mauro Giacca, Daniela Cesselli, Antonio Paolo Beltrami, Paolo Ascenzi, Silvia Zucchelli, Francesca Persichetti, Giampiero Leanza, Stefano Gustincich
Hemoglobin (Hb) is the major protein in erythrocytes and carries oxygen (O2) throughout the body. Recently, Hb has been found synthesized in atypical sites, including the brain. Hb is highly expressed in A9 dopaminergic (DA) neurons of the substantia nigra (SN), whose selective degeneration leads to Parkinson's disease (PD). Here we show that Hb confers DA cells' susceptibility to 1-methyl-4-phenylpyridinium (MPP(+)) and rotenone, neurochemical cellular models of PD. The toxic property of Hb does not depend on O2 binding and is associated with insoluble aggregate formation in the nucleolus...
January 5, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28049942/intranasal-administration-of-rotenone-to-mice-induces-dopaminergic-neurite-degeneration-of-dopaminergic-neurons-in-the-substantia-nigra
#9
Hitoshi Sasajima, Sadaharu Miyazono, Tomohiro Noguchi, Makoto Kashiwayanagi
Exposure to environmental neurotoxins is suspected to be a risk factor for sporadic progressive neurodegenerative diseases. Parkinson's disease has been associated with exposure to the pesticide rotenone, a mitochondrial respiration inhibitor. We previously reported that intranasal administration of rotenone in mice induced dopaminergic (DA) neurodegeneration in the olfactory bulb (OB) and reduced olfactory functions. In the present study, we investigated the DA neurons in the brains of mice that were administered rotenone intranasally for an extended period...
2017: Biological & Pharmaceutical Bulletin
https://www.readbyqxmd.com/read/28029694/type-i-interferons-mediate-the-neuroinflammatory-response-and-neurotoxicity-induced-by-rotenone
#10
Bevan S Main, Moses Zhang, Kate M Brody, Francis J Kirby, Peter J Crack, Juliet M Taylor
Evidence from post-mortem human brains, animal studies and cell culture models has implicated neuroinflammation in the aetiology of chronic neuropathologies including Alzheimer's and Parkinson's diseases. Although the neuroinflammatory response is considered detrimental in contributing to these pathologies, the underlying mechanisms are still not well understood. The type-I interferons (IFNs) have been well characterised in the periphery and are known to initiate/modulate the immune response. Recently, they have been implicated in aging and we have also demonstrated increased type-I IFN expression in post-mortem human Alzheimer's and Parkinson's disease brains...
December 28, 2016: Journal of Neurochemistry
https://www.readbyqxmd.com/read/28006942/propofol-induced-mitochondrial-and-contractile-dysfunction-of-the-rat-ventricular-myocardium
#11
M Grundmanová, D Jarkovská, A Süß, Z Tůma, M Marková, Z Grundman, A El-Kadi, M Čedíková, M Štengl, J Kuncová
Propofol is a short-acting hypnotic agent used in human medicine for sedation and general anesthesia. Its administration can be associated with serious cardiovascular side-effects that include decrease in arterial blood pressure and cardiac output. The aim of the present study was to evaluate propofol effects on mitochondrial respiration, myocardial contractility and electrophysiology in the same samples isolated from the heart ventricles of adult rats. Mitochondrial oxygen consumption was measured in permeabilized samples dissected from free walls of both ventricles using high-resolution respirometry...
December 22, 2016: Physiological Research
https://www.readbyqxmd.com/read/27997067/rotenone-and-elevated-extracellular-potassium-concentration-induce-cell-specific-fibrillation-of-%C3%AE-synuclein-in-axons-of-cholinergic-enteric-neurons-in-the-guinea-pig-ileum
#12
D F Sharrad, B N Chen, W P Gai, N Vaikath, O M El-Agnaf, S J H Brookes
BACKGROUND: Parkinson's disease is a progressive neurodegenerative disorder that results in the widespread loss of select classes of neurons throughout the nervous system. The pathological hallmarks of Parkinson's disease are Lewy bodies and neurites, of which α-synuclein fibrils are the major component. α-Synuclein aggregation has been reported in the gut of Parkinson's disease patients, even up to a decade before motor symptoms, and similar observations have been made in animal models of disease...
November 7, 2016: Neurogastroenterology and Motility: the Official Journal of the European Gastrointestinal Motility Society
https://www.readbyqxmd.com/read/27996361/insight-into-the-molecular-mechanism-of-p-glycoprotein-mediated-drug-toxicity-induced-by-bioflavonoids-an-integrated-computational-approach
#13
Pathomwat Wongrattanakamon, Vannajan Sanghiran Lee, Piyarat Nimmanpipug, Sunee Chansakaow, Supat Jiranusornkul
In this work, molecular docking, pharmacophore modelling, and molecular dynamics (MD) simulation were rendered for the mouse P-gp (code: 4Q9H) and bioflavonoids; amorphigenin, chrysin, epigallocatechin, formononetin, and rotenone including a positive control; verapamil to identify protein-ligand interaction features including binding affinities, interaction characteristics, hot-spot amino acid residues, and complex stabilities. These flavonoids occupied the same binding site with high binding affinities and shared the same key residues for their binding interactions and the binding region of the flavonoids was revealed that overlapped the ATP binding region with hydrophobic and hydrophilic interactions suggesting a competitive inhibition mechanism of the compounds...
December 20, 2016: Toxicology Mechanisms and Methods
https://www.readbyqxmd.com/read/27994808/effects-of-benzo-e-pyrene-on-reactive-oxygen-nitrogen-species-and-inflammatory-cytokines-induction-in-human-rpe-cells-and-attenuation-by-mitochondrial-involved-mechanism
#14
M Fernanda Estrago-Franco, M Tarek Moustafa, Mohammad Riazi-Esfahani, Ashish U Sapkal, Rhina Piche-Lopez, A Jayaprakash Patil, Ashish Sharma, Payam Falatoonzadeh, Marilyn Chwa, Georgia Luczy-Bachman, Baruch D Kuppermann, M Cristina Kenney
PURPOSE: To identify inhibitors that could effectively lower reactive oxygen/nitrogen species (ROS/RNS), complement and inflammatory cytokine levels induced by Benzo(e)pyrene [B(e)p], an element of cigarette smoke, in human retinal pigment epithelial cells (ARPE-19) in vitro. METHODS: ARPE-19 cells were treated for 24 hours with 200 μM, 100 μM, and 50 μM B(e)p or DMSO (dimethyl sulfoxide)-equivalent concentrations. Some cultures were pre-treated with ROS/RNS inhibitors (NG nitro-L-arginine, inhibits nitric oxide synthase; Apocynin, inhibits NADPH oxidase; Rotenone, inhibits mitochondrial complex I; Antimycin A, inhibits mitochondria complex III) and ROS/RNS levels were measured with a fluorescent H2 DCFDA assay...
October 2016: Journal of Ophthalmic & Vision Research
https://www.readbyqxmd.com/read/27986376/bilateral-upregulation-of-%C3%AE-synuclein-expression-in-the-mouse-substantia-nigra-by-intracranial-rotenone-treatment
#15
Candace H Carriere, Na Hyea Kang, Lennard P Niles
The pesticide rotenone has been shown to cause systemic inhibition of mitochondrial complex I activity, with consequent degeneration of dopamine neurons along the nigrostriatal pathway, as observed in Parkinson's disease (PD). Recently, intracranial infusion of rotenone was found to increase the protein levels of the Lewy body constituents, α-synuclein and small ubiquitin-related modifier-1(SUMO-1), in the lesioned hemisphere of the mouse brain. These findings are supportive of a mouse model of PD, but information about the dopamine-synthesizing enzyme, tyrosine hydroxylase (TH), an essential marker of dopaminergic status, was not reported...
December 13, 2016: Experimental and Toxicologic Pathology: Official Journal of the Gesellschaft Für Toxikologische Pathologie
https://www.readbyqxmd.com/read/27979718/neonatal-rotenone-lesions-cause-onset-of-hyperactivity-during-juvenile-and-adulthood-in-the-rat
#16
Masami Ishido, Junko Suzuki, Yoshinori Masuo
Attention deficit hyperactivity disorder (ADHD) is characterized by behavioral and cognitive symptoms. Longitudinal studies demonstrated that the symptoms remains clinically significant for the majority of ADHD children into adulthood. Furthermore, a population-based birth cohort provided the initial evidence of adult ADHD that lacks a history of childhood ADHD. We previously demonstrated that neonatal exposure to bisphenol A, an environmental chemical caused hyperactivity in the juvenile. Here, we extend to examine other chemical such as rotenone, a dopaminergic toxins...
January 15, 2017: Toxicology Letters
https://www.readbyqxmd.com/read/27937035/synthesis-and-neuroprotective-effects-of-the-complex-nanoparticles-of-iron-and-sapogenin-isolated-from-the-defatted-seeds-of-camellia-oleifera
#17
Qian Yang, Chuang Zhao, Jun Zhao, Yong Ye
CONTEXT: The defatted seeds of Camellia oleifera var. monosperma Hung T. Chang (Theaceae) are currently discarded without effective utilization. However, sapogenin has been isolated and shows antioxidative, anti-inflammatory and analgesic activities suggestive of its neuroprotective function. OBJECTIVE: In order to improve the activities of sapogenin, the nanoparticles of iron-sapogenin have been synthesized, and the neuroprotective effects are evaluated. MATERIALS AND METHODS: Structural characters of the nanoparticles were analyzed, and the antioxidant effect was assessed by DPPH method, and the neuroprotective effect was evaluated by rotenone-induced neurodegeneration in Kunming mice injected subcutaneously into the back of neck with rotenone (50 mg/kg/day) for 6 weeks and then treated by tail intravenous injection with the iron-sapogenin at the dose of 25, 50 and 100 mg/kg for 7 days...
December 2017: Pharmaceutical Biology
https://www.readbyqxmd.com/read/27932496/sonic-hedgehog-pathway-activation-increases-mitochondrial-abundance-and-activity-in-hippocampal-neurons
#18
Pamela J Yao, Uri Manor, Ronald S Petralia, Rebecca D Brose, Ryan T Y Wu, Carolyn Ott, Ya-Xian Wang, Ari Charnoff, Jennifer Lippincott-Schwartz, Mark P Mattson
Mitochondria are essential organelles whose biogenesis, structure, and function are regulated by many signaling pathways. In this study we present evidence that, in hippocampal neurons, activation of the Sonic hedgehog (Shh) signaling pathway impacts multiple aspects of mitochondria. Mitochondrial mass was increased significantly in neurons treated with Shh. Using biochemical and fluorescence imaging analyses, we show that Shh signaling activity reduces mitochondrial fission and promotes mitochondrial elongation, at least in part, via suppression of the mitochondrial fission protein dynamin-like GTPase Drp1...
December 8, 2016: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/27910179/stereocontrolled-total-syntheses-of-rotenone-and-dalpanol-by-1-2-rearrangement-and-sn-ar-oxycyclizations
#19
Kayo Nakamura, Ken Ohmori, Keisuke Suzuki
The total syntheses of (-)-rotenone and (-)-dalpanol have been achieved by a group-selective, stereospecific 1,2-shift of an epoxy alcohol and SN Ar cyclizations. Three oxacycles are constructed, thus illustrating a versatile synthetic route to various rotenoids.
January 2, 2017: Angewandte Chemie
https://www.readbyqxmd.com/read/27901474/cerebellar-neurochemical-and-histopathological-changes-in-rat-model-of-parkinson-s-disease-induced-by-intrastriatal-injection-of-rotenone
#20
Yasser A Khadrawy, Iman M Mourad, Haitham S Mohammed, Neveen A Noor, Heba S Aboul Ezz
The aim of the present work was to investigate the neurochemical changes induced in the cerebellum of rat model of Parkinson's disease (PD). Rats were divided into two groups; control and rat model of PD induced by the intrastriatal injection of rotenone. As compared to control, a significant increase in the excitatory amino acid neurotransmitters; glutamate and aspartate together with a significant decrease in the inhibitory amino acids, GABA, glycine and taurine were observed in the cerebellum of rat model of PD...
January 2017: General Physiology and Biophysics
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