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https://www.readbyqxmd.com/read/28534083/synthetic-alpha-synuclein-fibrils-cause-mitochondrial-impairment-and-selective-dopamine-neurodegeneration-in-part-via-inos-mediated-nitric-oxide-production
#1
Victor Tapias, Xiaoping Hu, Kelvin C Luk, Laurie H Sanders, Virginia M Lee, J Timothy Greenamyre
Intracellular accumulation of α-synuclein (α-syn) are hallmarks of synucleinopathies, including Parkinson's disease (PD). Exogenous addition of preformed α-syn fibrils (PFFs) into primary hippocampal neurons induced α-syn aggregation and accumulation. Likewise, intrastriatal inoculation of PFFs into mice and non-human primates generates Lewy bodies and Lewy neurites associated with PD-like neurodegeneration. Herein, we investigate the putative effects of synthetic human PFFs on cultured rat ventral midbrain dopamine (DA) neurons...
May 22, 2017: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/28533741/adulthood-exposure-to-lipopolysaccharide-exacerbates-the-neurotoxic-and-inflammatory-effects-of-rotenone-in-the-substantia-nigra
#2
Chun Huang, Li Zhu, Huan Li, Fu-Guo Shi, Guo-Qing Wang, Yi-Zheng Wei, Jie Liu, Feng Zhang
Parkinson's disease (PD) is the second most neurodegenerative disorder with a regional decrease of dopamine (DA) neurons in the substantia nigra (SN). Despite intense exploration, the etiology of PD progressive process remains unclear. This study was to investigate the synergistic effects of systemic inflammation of lipopolysaccharide (LPS) and neurotoxicity of rotenone (ROT) on exacerbating DA neuron lesion. Male SD adulthood rats received a single intraperitoneal injection of LPS. Seven months later, rats were subcutaneously given ROT five times a week for consecutive 4 weeks...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28532211/rotenone-induces-nephrotoxicity-in-rats-oxidative-damage-and-apoptosis
#3
Xiao-Wen Jiang, Lu Qiao, Xin-Xin Feng, Lin Liu, Qing-Wei Wei, Xue-Wei Wang, Wen-Hui Yu
Previous studies have examined rotenone toxicity on the human central nervous system, especially in the pathogenesis of Parkinson's disease, but few have investigated the effects of rotenone on the kidney. Here, rotenone-induced nephrotoxicity was evaluated by determining morphological, biochemical, oxidative stress-related, and apoptotic factor alterations in rat renal tissue. Morphological and biochemical analyses showed that rotenone administration to rats damaged renal tissue. Western blot results revealed that rotenone induced oxidative damage, causing overproduction of glutathione, malonaldehyde, and reactive oxygen species (ROS), and inhibiting superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activity...
May 22, 2017: Toxicology Mechanisms and Methods
https://www.readbyqxmd.com/read/28527718/rotenone-decreases-ischemia-induced-injury-by-inhibiting-mitochondrial-permeability-transition-in-mature-brains
#4
Evelina Rekuviene, Laima Ivanoviene, Vilmante Borutaite, Ramune Morkuniene
The mitochondrial permeability transition pore (mPTP) is thought to be implicated in brain ischemia-induced cell death. Here we sought to determine whether complex I (CI) of the mitochondrial electron transfer system may be involved in regulation of mPTP opening during ischemia and whether a specific inhibitor of this complex - rotenone can protect against ischemia-induced cell death in an experimental model of total ischemia in adult rat brains. Anesthetized Wistar rats were administered a single injection of rotenone (0...
May 17, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/28526446/thymoquinone-exerts-neuroprotective-effect-in-animal-model-of-parkinson-s-disease
#5
Seyedeh Shohreh Ebrahimi, Shahrbanoo Oryan, Esmael Izadpanah, Kambiz Hassanzadeh
Oxidative stress plays an important role in both the initiation and progression of Parkinson's disease (PD). Rotenone, an environmental toxin, induces oxidative stress and impact mitochondrial dynamics, including fission and fusion. Thymoquinone (TQ) has been reported to have antioxidant and anti-inflammatory characteristics in vitro and in vivo. TQ scavenges free radicals so prevents cell damage against oxidative agents. To evaluate the efficacy of TQ in the management of PD, male Wistar rats (8-10 months) received rotenone...
May 16, 2017: Toxicology Letters
https://www.readbyqxmd.com/read/28523458/the-respiratory-chain-inhibitor-rotenone-affects-peroxisomal-dynamics-via-its-microtubule-destabilising-activity
#6
Josiah B Passmore, Sonia Pinho, Maria Gomez-Lazaro, Michael Schrader
Peroxisomes and mitochondria in mammalian cells are closely linked subcellular organelles, which maintain a redox-sensitive relationship. Their interplay and role in ROS signalling are supposed to impact on age-related and degenerative disorders. Whereas the generation of peroxisome-derived oxidative stress can affect mitochondrial morphology and function, little is known about the impact of mitochondria-derived oxidative stress on peroxisomes. Here, we investigated the effect of the mitochondrial complex I inhibitor rotenone on peroxisomal and mitochondrial membrane dynamics...
May 18, 2017: Histochemistry and Cell Biology
https://www.readbyqxmd.com/read/28511367/neurobehavioural-changes-in-a-hemiparkinsonian-rat-model-induced-by-rotenone
#7
REVIEW
Sukala Puthuparambil Maniyath, Narayanan Solaiappan, Muthusamy Rathinasamy
INTRODUCTION: Rotenone, a mitochondrial complex I inhibitor is used as a neurotoxin agent to reproduce the neuropathological, and behavioural feature of Parkinson's Disease (PD) in rat. Due to acute and chronic exposure of rotenone with various doses through different routes of administration, mortality is being reported. Low dose takes a longer duration to produce PD symptoms in animals. This present study was designed to create hemiparkinsonian 'partial' lesion model by rotenone at a single moderate dose in two sites of striatum in albino rats and also to assess its toxicity by behavioural parameters and by microscopic study...
March 2017: Journal of Clinical and Diagnostic Research: JCDR
https://www.readbyqxmd.com/read/28506882/examination-of-the-superoxide-hydrogen-peroxide-forming-and-quenching-potential-of-mouse-liver-mitochondria
#8
Liam Slade, Julia Chalker, Nidhi Kuksal, Adrian Young, Danielle Gardiner, Ryan J Mailloux
Pyruvate dehydrogenase (PDHC) and α-ketoglutarate dehydrogenase complex (KGDHC) are important sources of reactive oxygen species (ROS). In addition, it has been found that mitochondria can also serve as sinks for cellular hydrogen peroxide (H2O2). However, the ROS forming and quenching capacity of liver mitochondria has never been thoroughly examined. Here, we show that mouse liver mitochondria use catalase, glutathione (GSH), and peroxiredoxin (PRX) systems to quench ROS. Incubation of mitochondria with catalase inhibitor 3-amino-1,2,4-triazole (triazole) induced a significant increase in pyruvate or α-ketoglutarate driven O2(●-)/H2O2 formation...
May 12, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28503732/imaging-short-lived-reactive-oxygen-species-ros-with-endogenous-contrast-mri
#9
Rong-Wen Tain, Alessandro M Scotti, Weiguo Li, Xiaohong Joe Zhou, Kejia Cai
PURPOSE: To characterize the relaxation properties of reactive oxygen species (ROS) for the development of endogenous ROS contrast magnetic resonance imaging (MRI). MATERIALS AND METHODS: ROS-producing phantoms and animal models were imaged at 9.4T MRI to obtain T1 and T2 maps. Egg white samples treated with varied concentrations of hydrogen peroxide (H2 O2 ) were used to evaluate the effect of produced ROS in T1 and T2 for up to 4 hours. pH and temperature changes due to H2 O2 treatment in egg white were also monitored...
May 15, 2017: Journal of Magnetic Resonance Imaging: JMRI
https://www.readbyqxmd.com/read/28503522/treadmill-exercise-alleviates-depressive-symptoms-in-rotenone-induced-parkinson-disease-rats
#10
Mal-Soon Shin, Tae-Woon Kim, Jae-Min Lee, Yun-Hee Sung, Baek-Vin Lim
Parkinson disease (PD) is characterized by selective loss of the dopaminergic neurons. The symptoms of depression following PD are closely associated with reduced activity of the serotonergic system in the dorsal raphe. We explored the antidepressive effect of exercise and its possible mechanism using the rotenone-induced PD rats. PD rats were induced by subcutaneously injection with rotenone for 14 days. The rats in the exercise groups were made to run on a treadmill for 30 min once a day during 14 consecutive days...
April 2017: Journal of Exercise Rehabilitation
https://www.readbyqxmd.com/read/28502703/cell-death-induced-by-mitochondrial-complex-i-inhibition-is-mediated-by-iron-regulatory-protein-1
#11
Pamela J Urrutia, Pabla Aguirre, Victoria Tapia, Carlos M Carrasco, Natalia P Mena, Marco T Núñez
Mitochondrial dysfunction and oxidative damage, often accompanied by elevated intracellular iron levels, are pathophysiological features in a number of neurodegenerative processes. The question arises as to whether iron dyshomeostasis is a consequence of mitochondrial dysfunction. Here we have evaluated the role of Iron Regulatory Protein 1 (IRP1) in the death of SH-SY5Y dopaminergic neuroblastoma cells subjected to mitochondria complex I inhibition. We found that complex I inhibition was associated with increased levels of transferrin receptor 1 (TfR1) and iron uptake transporter divalent metal transporter 1 (DMT1), and decreased levels of iron efflux transporter Ferroportin 1 (FPN1), together with increased (55)Fe uptake activity and an increased cytoplasmic labile iron pool...
May 11, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28482088/therapeutic-concentrations-of-antidepressants-inhibit-pancreatic-beta-cell-function-via-mitochondrial-complex-inhibition
#12
Ekramy Elmorsy, Ayat Al-Ghafari, Ahmed N M Helaly, Ahmed S Hisab, Bettina Oehrle, Paul A Smith
Diabetes mellitus risk is increased by prolonged usage of antidepressants (ADs). Although various mechanisms are suggested for their diabetogenic potential, whether a direct effect of ADs on pancreatic β-cells is involved is unclear. We examined this idea for three ADs: paroxetine, clomipramine and, with particular emphasis, fluoxetine, on insulin secretion, mitochondrial function, cellular bioenergetics, KATP channel activity and caspase activity in murine and human cell-line models of pancreatic β-cells...
May 8, 2017: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/28480622/roles-of-nadph-oxidase-and-mitochondria-in-flow-induced-vasodilation-of-human-adipose-arterioles-ros-induced-ros-release-in-coronary-artery-disease
#13
Natalya S Zinkevich, Ibra S Fancher, David D Gutterman, Shane A Phillips
OBJECTIVES: Hydrogen peroxide (H2 O2 ) contributes to flow-induced dilation (FID) of human arterioles. This study is designed to examine the roles of mitochondria and NADPH oxidase in modulating the release of ROS and in mediating FID. We tested whether NADPH oxidase contributes to mitochondrial ROS generation in arterioles during coronary artery disease (CAD). METHODS: Visceral adipose arterioles obtained from patients with or without CAD were cannulated and pressurized for videomicroscopic measurement of arteriolar diameters...
May 8, 2017: Microcirculation: the Official Journal of the Microcirculatory Society, Inc
https://www.readbyqxmd.com/read/28475928/development-and-characterization-of-mitochondrial-membrane-affinity-chromatography-columns-derived-from-skeletal-muscle-and-platelets-for-the-study-of-mitochondrial-transmembrane-proteins
#14
Nagendra Surendra Singh, Kaia-Liisa Habicht, Ruin Moaddel, Ruth Shimmo
Mitochondrial membrane fragments from human platelets and monkey skeletal muscles were successfully immobilized onto immobilized artificial membrane chromatographic support for the first time, resulting in mitochondrial membrane affinity chromatography (MMAC) columns. These columns were validated by characterization of translocator protein (TSPO), where multiple concentrations of dipyridamole were run and the binding affinities (Kd) determined. Further, the relative ranking data of TSPO ligands was consistent with previously reported rankings for both, the platelet (MMAC-Platelet) and the skeletal muscle (MMAC-Muscle) column (dipyridamole>PK11195>protoporphyrin IX>rotenone)...
April 13, 2017: Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences
https://www.readbyqxmd.com/read/28471847/neuroprotective-effect-of-resveratrol-on-rotenone-treated-c57bl-6-mice
#15
Xiaofei Zhao, Jun Wang, Song Hu, Renping Wang, Yongjun Mao, Junxia Xie
The aim of the present study was to investigate whether resveratrol could reduce nigral iron levels to prevent the degeneration of dopaminergic neurons in the substantia nigra (SN) of C57BL/6 mice induced by rotenone. Parkinson's disease (PD) is an age-related neurodegenerative disorder; elevated iron levels in the SN participate in neuronal death in PD. Resveratrol is a kind of polyphenolic compounds and possess antioxidant, anticancer, and anti-inflammatory biological functions. Although many research groups have investigated the neuroprotective effects of resveratrol against PD, the precise mechanisms underlying its beneficial effects on dopaminergic neuron are poorly defined...
June 14, 2017: Neuroreport
https://www.readbyqxmd.com/read/28470519/assaying-mitochondrial-respiration-as-an-indicator-of-cellular-metabolism-and-fitness
#16
Natalia Smolina, Joseph Bruton, Anna Kostareva, Thomas Sejersen
Mitochondrial respiration is the most important generator of cellular energy under most circumstances. It is a process of energy conversion of substrates into ATP. The Seahorse equipment allows measuring oxygen consumption rate (OCR) in living cells and estimates key parameters of mitochondrial respiration in real-time mode. Through use of mitochondrial inhibitors, four key mitochondrial respiration parameters can be measured: basal, ATP production-linked, maximal, and proton leak-linked OCR. This approach requires application of mitochondrial inhibitors-oligomycin to block ATP synthase, FCCP-to make the inner mitochondrial membrane permeable for protons and allow maximum electron flux through the electron transport chain, and rotenone and antimycin A-to inhibit complexes I and III, respectively...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28466394/involvement-of-c-abl-kinase-in-microglial-activation-of-nlrp3-inflammasome-and-impairment-in-autolysosomal-system
#17
Vivek Lawana, Neeraj Singh, Souvarish Sarkar, Adhithiya Charli, Huajun Jin, Vellareddy Anantharam, Anumantha G Kanthasamy, Arthi Kanthasamy
A growing body of evidence suggests that excessive microglial activation and pesticide exposure may be linked to the etiology of PD; however, the mechanisms involved remain elusive. Emerging evidence indicates that intracellular inflammasome complex namely NLRP3 complex is involved in the recognition and execution of host inflammatory response. Thus, in the present study, we investigated the hypothesis that NLRP3 inflammasome activation is linked to rotenone (ROT)-induced microglial activation which is dependent upon a priming stimulus by a pathogen-associated molecular pattern (PAMP) or damage associated molecular pattern (DAMP), respectively...
May 2, 2017: Journal of Neuroimmune Pharmacology: the Official Journal of the Society on NeuroImmune Pharmacology
https://www.readbyqxmd.com/read/28466269/pdgf-bb-preserves-mitochondrial-morphology-attenuates-ros-production-and-upregulates-neuroglobin-in-an-astrocytic-model-under-rotenone-insult
#18
Ricardo Cabezas, Nelson E Vega-Vela, Juliana González-Sanmiguel, Janneth González, Paula Esquinas, Valentina Echeverria, George E Barreto
Platelet-derived growth factor, subtype BB (PDGF-BB) is a mitogenic growth factor produced in different cell types such as platelets, fibroblasts, neurons, and astrocytes. Previous reports have shown that different PDGF isoforms exert a neuroprotective effect in neurons and astrocytes against multiple degenerative insults. Previously, we showed that pretreatment with PDGF-BB for 24 h increased cell viability, preserved nuclear morphology and mitochondrial membrane potential following stimulation with rotenone, and reduced free radical production nearly to control conditions...
May 2, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28450929/effect-of-intranasal-stem-cell-administration-on-the-nigrostriatal-system-in-a-mouse-model-of-parkinson-s-disease
#19
Mohamed Salama, Mahmoud Sobh, Mahmoud Emam, Ahmed Abdalla, Dina Sabry, Mohamed El-Gamal, Ahmed Lotfy, Mahmoud El-Husseiny, Mohamed Sobh, Ali Shalash, Wael My Mohamed
Parkinson's disease (PD) is the second most common neurodegenerative disease worldwide. It affects the locomotor system, leading to a final severe disability through degeneration of dopaminergic neurons. Despite several therapeutic approaches used, no treatment has been proven to be effective; however, cell therapy may be a promising therapeutic method. In addition, the use of the intranasal (IN) route has been advocated for delivering various therapies to the brain. In the present study, the IN route was used for administration of mesenchymal stem cells (MSCs) in a mouse model of PD, with the aim to evaluate IN delivery as an alternative route for cell based therapy administration in PD...
March 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28445961/azilsartan-ameliorates-apoptosis-of-dopaminergic%C3%A2-neurons-and-rescues-characteristic-parkinsonian-behaviors-in-a-rat-model-of-parkinson-s-disease
#20
Qing Gao, Zhou Ou, Teng Jiang, You-Yong Tian, Jun-Shan Zhou, Liang Wu, Jian-Quan Shi, Ying-Dong Zhang
Loss of dopaminergic neurons within the substantia nigra (SN) is a pathological hallmark of Parkinson's disease (PD), which leads to the onset of motor symptoms. Previously, our in vitro studies revealed that Angiotensin II (Ang II) induced apoptosis of dopaminergic neurons through its type 1 receptor (AT1R), but these findings needed to be confirmed via animal experiments. Here, using a rotenone-induced rat model of PD, we observed an overactivation of Ang II/AT1R axis in the SN, since Ang II level and AT1R expression were markedly increased...
April 11, 2017: Oncotarget
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