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Zuriñe Antón, Ane Landajuela, Javier H Hervás, L Ruth Montes, Sonia Hernández-Tiedra, Guillermo Velasco, Felix M Goñi, Alicia Alonso
The phospholipid cardiolipin (CL) has been proposed to play a role in selective mitochondrial autophagy, or mitophagy. CL externalization to the outer mitochondrial membrane would act as a signal for the human Atg8 ortholog subfamily, MAP1LC3 (LC3). The latter would mediate both mitochondrial recognition and autophagosome formation, ultimately leading to removal of damaged mitochondria. We have applied quantitative biophysical techniques to the study of CL interaction with various Atg8 human orthologs, namely LC3B, GABARAPL2 and GABARAP...
October 20, 2016: Autophagy
Alina Constantin, Madalina Dumitrescu, Maria Cristina Mihai Corotchi, Dana Jianu, Maya Simionescu
CO2 laser has a beneficial effect on stem cells by mechanisms that are not clearly elucidated. We hypothesize that the effect of fractional CO2 laser on human adipose-derived stem cells (ADSC) could be due to changes in redox homeostasis and secretion of factors contributing to cellular proliferation and angiogenic potential. ADSC incubated in medium containing 0.5 or 10 % FBS were exposed to a single irradiation of a 10,600-nm fractional CO2 laser; non-irradiated ADSC were used as control. Viability/proliferation of ADSC was assessed by MTT assay; the intracellular reactive oxygen species (ROS) levels and the mitochondrial membrane potential (∆Ψm) were determined with DCFH-DA and JC-1 fluorescent probes, respectively...
October 20, 2016: Lasers in Medical Science
Michel van Schaardenburgh, Martin Wohlwend, Øivind Rognmo, Erney J R Mattsson
PURPOSE: Mitochondria are essential for energy production in the muscle cell and for this they are dependent upon a sufficient supply of oxygen by the circulation. Exercise training has shown to be a potent stimulus for physiological adaptations and mitochondria play a central role. Whether changes in mitochondrial respiration are seen after exercise in patients with a reduced circulation is unknown. The aim of the study was to evaluate the time course and whether one session of calf raise exercise stimulates mitochondrial respiration in the calf muscle of patients with peripheral vascular disease...
2016: PloS One
Alexandre N Rcom-H'cheo-Gauthier, Amelia Davis, Adrian C B Meedeniya, Dean L Pountney
α-Synuclein (α-syn) aggregates (Lewy bodies) in dementia with Lewy Bodies (DLB) may be associated with disturbed calcium homeostasis and oxidative stress. We investigated the interplay between α-syn aggregation, expression of the calbindin-D28k (CB) neuronal calcium-buffering protein and oxidative stress, combining immunofluorescence double labelling and Western analysis, and examining DLB and normal human cases and a unilateral oxidative stress lesion model of α-syn disease (rotenone mouse). DLB cases showed a greater proportion of CB+ cells in affected brain regions compared to normal cases with Lewy bodies largely present in CB- neurons and virtually undetected in CB+ neurons...
October 13, 2016: Molecular and Cellular Neurosciences
Hesti Lina Wiraswati, Emilie Hangen, Ana Belén Sanz, Ngoc-Vy Lam, Camille Reinhardt, Allan Sauvat, Ariane Mogha, Alberto Ortiz, Guido Kroemer, Nazanine Modjtahedi
Mitochondrial apoptosis inducing factor (AIF) is a redox-active enzyme that participates to the biogenesis/maintenance of complex I of the respiratory chain, yet also contributes to catabolic reactions in the context of regulated cell death when AIF translocates to the cytosol and to the nucleus. Here we explore the contribution of AIF to cell death induced by menadione (2-methyl-1,4-naphtoquinone; also called vitamin K3) in conditions in which this pro-oxidant does not cause the mitochondrial release of AIF, yet causes caspase-independent cell killing...
October 11, 2016: Oncotarget
Hongxiang Sun, Xiuquan He, Cejia Liu, Lingyu Li, Ruoyu Zhou, Tianyun Jin, Su Yue, Da Feng, Jie Gong, Jiawei Sun, Jianbo Ji, Lan Xiang
Oleracein E (OE), a tetrahydroisoquinoline possessing potent anti-oxidant activity, was first isolated from a traditional Chinese medicine, Portulaca oleraea L., and is hypothesized to be a neuroprotectant. In the present study, we evaluated the effects of racemic OE on rotenone-induced toxicity in Parkinson's disease (PD) cell and animal models. Pre-treatment with OE (10 μM, 2 h) decreased LDH release and the apoptosis rate in rotenone (5 μM, 24 h)-treated SH-SY5Y human neuroblastoma cells. Further mechanistic study indicated that OE reduced reactive oxygen species (ROS) levels, inhibited ERK1/2 phosphorylation, reduced rotenone-induced up-regulation of the proapoptotic protein Bax, and prevented cytochrome C release and caspase-3 activation...
October 12, 2016: ACS Chemical Neuroscience
Ying Gao, Xu Wang, Chunnian He
ETHNOPHARMACOLOGICAL RELEVANCE: Reactive oxygen species (ROS) mediate vascular cell dysfunction and lead to atherosclerosis and other chronic cardiovascular diseases. The root of Pueraria lobata (Willd.) Ohwi, also known as kudzu or Gegen (Chinese name), is one of the most important herbs in traditional Chinese medicine and has been widely used in the treatment of cardiovascular diseases, diabetes, osteonecrosis and neurodegradation diseases. In this study, an ethanol extract from kudzu root was prepared and the in vitro protective effect of the kudzu root extract (KUD) on human umbilical vein endothelial cells (HUVECs) was investigated...
October 4, 2016: Journal of Ethnopharmacology
Michael F Almeida, Carolliny M Silva, Aline M D'Unhao, Merari F R Ferrari
Cell physiology is impaired before protein aggregation and this may be more relevant than inclusions themselves for neurodegeneration. The present study aimed to characterize an animal model to enable the analysis of the cell biology before and after protein aggregation. Ten-month-old Lewis rats were exposed either to 1 or 2 mg/kg/day of rotenone, delivered subcutaneously through mini-pumps, for one month. Hyperphosphorylated TAU, alpha-synuclein, amyloid-beta peptide and protein carbonylation (indicative of oxidative stress) were evaluated in the hippocampus, substantia nigra and locus coeruleus through immunohistochemistry or western blot...
September 2016: Arquivos de Neuro-psiquiatria
Zhimin Wang, Jiajia Wu, Xuelian Yang, Pei Cai, Qiaohong Liu, Kelvin D G Wang, Lingyi Kong, Xiaobing Wang
The benzyloxy substituted small molecules are well-known highly potent monoamine oxidase B inhibitors, but their therapeutic potential against Parkinson's disease have not been investigated in detail. In this paper, a series of representative benzyloxy substituted derivatives were synthesized and evaluated for MAO-A/B inhibition. In addition, their neuroprotective effects were investigated in 6-OHDA- and rotenone-treated PC12 cells. It was observed that most of the compounds exhibited a marked increase in survival of PC12 cells which treated with the neurotoxins...
September 21, 2016: Bioorganic & Medicinal Chemistry
Han Liu, Chunlei Yu, Tianjiao Xu, Xiaojie Zhang, Miaoxian Dong
There are several factors, like oxidative stress and neurons loss, involving neurodegenerative diseases such as Parkinson's disease (PD). The combination of antioxidant and anti-apoptotic agent is becoming a promising approach to fight against PD. This study evaluates the hypothesis that paeoniflorin (PF) and β-ecdysterone (β-Ecd) synergize to protect PC12 cells against toxicity induced by PD-related neurotoxin rotenone. The combination of PF and β-Ecd, hereafter referred to as the PF/β-Ecd, at suboptimal concentrations increased the viability of rotenone-exposed PC12 cells in a synergistic manner...
September 29, 2016: Apoptosis: An International Journal on Programmed Cell Death
Nihar J Mehta, Karam Asmaro, David J Hermiz, Meredith M Njus, Ashraf H Saleh, Karen A Beningo, David Njus
The dopamine oxidation product cysteinyl-dopamine has attracted attention as a contributor to the death of dopaminergic neurons in Parkinson's disease. Treatment of cysteinyl-dopamine with hypochlorite yields an even more cytotoxic product. This product has potent redox-cycling activity and initiates production of superoxide in PC12 cells. Taurine, which scavenges hypochlorite, protects PC12 cells from cysteinyl-dopamine but not from the hypochlorite product, suggesting that the product, not cysteinyl-dopamine itself, is toxic...
September 25, 2016: Free Radical Biology & Medicine
Ngonidzashe B Madungwe, Netanel F Zilberstein, Yansheng Feng, Jean C Bopassa
Reactive oxygen species (ROS) generation has been implicated in many pathologies including ischemia/reperfusion (I/R) injury. This led to multiple studies on antioxidant therapies to treat cardiovascular diseases but paradoxically, results have so far been mixed as ROS production can be beneficial as a signaling mechanism and in cardiac protection via preconditioning interventions. We investigated whether the differential impact of increased ROS in injury as well as in protection could be explained by their site of production on the mitochondrial electron transport chain...
2016: American Journal of Cardiovascular Disease
Peng Zhao, Xiaoxia Yang, Liu Yang, Minshu Li, Kristofer Wood, Qiang Liu, Xiaodong Zhu
Parkinson's disease (PD) is characterized by a progressive loss of dopaminergic neurons with limited treatment options. Emerging evidence shows that FTY720 protects against neural injury via modulation of the S1P1 receptor. However, it remains unclear whether FTY720 could influence neurodegeneration in PD. Therefore, the present study was designed to determine the impact of fingolimod (FTY720), a sphingosine-1-phosphate receptor (S1PR) agonist, on 2 mouse models of PD. We found that FTY720 significantly reduced the deficit of motor function, diminished the loss of tyrosine hydroxylase-positive neurons in the substantia nigra, and attenuated the decrease of striatal dopamine and metabolite levels in mice receiving 6-hydroxydopamine (6-OHDA) or rotenone to simulate PD...
September 26, 2016: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
Evanna L Mills, Beth Kelly, Angela Logan, Ana S H Costa, Mukund Varma, Clare E Bryant, Panagiotis Tourlomousis, J Henry M Däbritz, Eyal Gottlieb, Isabel Latorre, Sinéad C Corr, Gavin McManus, Dylan Ryan, Howard T Jacobs, Marten Szibor, Ramnik J Xavier, Thomas Braun, Christian Frezza, Michael P Murphy, Luke A O'Neill
Activated macrophages undergo metabolic reprogramming, which drives their pro-inflammatory phenotype, but the mechanistic basis for this remains obscure. Here, we demonstrate that upon lipopolysaccharide (LPS) stimulation, macrophages shift from producing ATP by oxidative phosphorylation to glycolysis while also increasing succinate levels. We show that increased mitochondrial oxidation of succinate via succinate dehydrogenase (SDH) and an elevation of mitochondrial membrane potential combine to drive mitochondrial reactive oxygen species (ROS) production...
October 6, 2016: Cell
Du Fang, Yu Qing, Shijun Yan, Doris Chen, Shirley ShiDu Yan
Mitochondria are critical to neurogenesis, but the mechanisms of mitochondria in neurogenesis have not been well explored. We fully characterized mitochondrial alterations and function in relation to the development of human induced pluripotent stem cell (hiPSC)-derived dopaminergic (DA) neurons. Following directed differentiation of hiPSCs to DA neurons, mitochondria in these neurons exhibit pronounced changes during differentiation, including mature neurophysiology characterization and functional synaptic network formation...
October 11, 2016: Stem Cell Reports
Hayate Javed, Mohammad Amjad Kamal, Shreesh Ojha
Parkinson's disease (PD) is a devastating and progressive movement disorder characterized by symptoms of muscles rigidity, tremor, postural instability and slow physical movements. Biochemically, PD is characterized by lack of dopamine production and its action due to loss of dopaminergic neurons and neuropathologically by the presence of intracytoplasmic inclusions known as Lewy bodies, which mainly consist of presynaptic neuronal protein, α-synuclein (α-syn). It is believed that alteration in α-syn homeostasis leads to increased accumulation and aggregation of α-syn in Lewy body...
September 20, 2016: CNS & Neurological Disorders Drug Targets
Veerappan Venkatesh Gobi, Srinivasagam Rajasankar, Muthu Ramkumar, Chinnasamy Dhanalakshmi, Thamilarasan Manivasagam, Arokiasamy Justin Thenmozhi, Musthafa Mohamed Essa, Ranganathan Chidambaram
The present study was aimed to find out the effect of Agaricus blazei mushroom extract against rotenone-induced cellular model. SH-SY5Y neuroblastoma cells are divided into four experimental groups (control, rotenone (100 nM), A. blazei (5 μg/ml) + rotenone (100 nM), and A. blazei alone treated) based on MTT assay, cells were allowed to measure the ROS, TBARS levels, and antioxidants activities. Finally, mitochondrial transmembrane potential (MMP) and expressions of apoptotic proteins were also analyzed...
September 20, 2016: Nutritional Neuroscience
Paromita Kundu, Manasi Das, Kalpalata Tripathy, Sanjeeb K Sahoo
Parkinson's disease (PD) is the most widespread form of dementia where there is an age related degeneration of dopaminergic neurons in the substantia nigra region of the brain. Accumulation of α-synuclein (αS) protein aggregate, mitochondrial dysfunction, oxidative stress, and neuronal cell death are the pathological hallmarks of PD. In this context, amalgamation of curcumin and piperine having profound cognitive properties, and antioxidant activity seems beneficial. However, the blood-brain barrier (BBB) is the major impediment for delivery of neurotherapeutics to the brain...
October 3, 2016: ACS Chemical Neuroscience
Juan Manuel Chao de la Barca, Gilles Simard, Patrizia Amati-Bonneau, Zainab Safiedeen, Delphine Prunier-Mirebeau, Stéphanie Chupin, Cédric Gadras, Lydie Tessier, Naïg Gueguen, Arnaud Chevrollier, Valérie Desquiret-Dumas, Marc Ferré, Céline Bris, Judith Kouassi Nzoughet, Cinzia Bocca, Stéphanie Leruez, Christophe Verny, Dan Miléa, Dominique Bonneau, Guy Lenaers, M Carmen Martinez, Vincent Procaccio, Pascal Reynier
Leber's hereditary optic neuropathy (MIM#535000), the commonest mitochondrial DNA-related disease, is caused by mutations affecting mitochondrial complex I. The clinical expression of the disorder, usually occurring in young adults, is typically characterized by subacute, usually sequential, bilateral visual loss, resulting from the degeneration of retinal ganglion cells. As the precise action of mitochondrial DNA mutations on the overall cell metabolism in Leber's hereditary optic neuropathy is unknown, we investigated the metabolomic profile of the disease...
September 15, 2016: Brain: a Journal of Neurology
Jiawen Yuan, Jinpeng Ren, Ying Wang, Xiao He, Yuwu Zhao
Parkinson's disease (PD) is characterized by the progressive degeneration of the dopaminergic neurons in the substantia nigra (SN) region. Acteoside has displayed multiple biological functions. Its potential role against PD and the underlying signaling mechanisms are largely unknown. Here, we showed that oral administration of acteoside significantly attenuated parkinsonism symptoms in rotenone-induced PD rats. Further, acteoside inhibited rotenone-induced α-synuclein, caspase-3 upregulation and microtubule-associated protein 2 (MAP2) downregulation in PD rats...
2016: PloS One
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