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  1 / 21832 MEDLINE  
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[PMID]:28460583
[Au] Autor:Nielsen BS; Larsen EH; Ladefoged O; Lam HR
[Ad] Endereço:1 Environment and Toxicology, DHI, Hørsholm, Denmark.
[Ti] Título:Subchronic, Low-Level Intraperitoneal Injections of Manganese (IV) Oxide and Manganese (II) Chloride Affect Rat Brain Neurochemistry.
[So] Source:Int J Toxicol;36(3):239-251, 2017 May/Jun.
[Is] ISSN:1092-874X
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Manganese (Mn) is neurotoxic and can induce manganism, a Parkinson-like disease categorized as being a serious central nervous system irreversible neurodegenerative disease. An increased risk of developing symptoms of Parkinson disease has been linked to work-related exposure, for example, for workers in agriculture, horticulture, and people living near areas with frequent use of Mn-containing pesticides. In this study, the focus was placed on neurochemical effects of Mn. Rats were dosed intraperitoneally with 0.9% NaCl (control), 1.22 mg Mn (as MnO )/kg bodyweight (bw)/day, or 2.5 mg Mn (as MnCl )/kg bw/day for 7 d/wk for 8 or 12 weeks. This dosing regimen adds relevant new knowledge about Mn neurotoxicity as a consequence of low-dose subchronic Mn dosing. Manganese concentrations increased in the striatum, the rest of the brain, and in plasma, and regional brain neurotransmitter concentrations, including noradrenaline, dopamine (DA), 5-hydroxytrytamine, glutamate, taurine, and γ-amino butyric acid, and the activity of acetylcholinesterase changed. Importantly, a target parameter for Parkinson disease and manganism, the striatal DA concentration, was reduced after 12 weeks of dosing with MnCl . Plasma prolactin concentration was not significantly affected due to a potentially reduced dopaminergic inhibition of the prolactin release from the anterior hypophysis. No effects on the striatal α-synuclein and synaptophysin protein levels were detected.
[Mh] Termos MeSH primário: Química Encefálica/efeitos dos fármacos
Encéfalo/efeitos dos fármacos
Cloretos/toxicidade
Óxidos/toxicidade
[Mh] Termos MeSH secundário: Acetilcolinesterase/metabolismo
Animais
Encéfalo/metabolismo
Cloretos/sangue
Cloretos/farmacocinética
Dopamina/metabolismo
Ácido Glutâmico/metabolismo
Injeções Intraperitoneais
Masculino
Manganês/sangue
Manganês/metabolismo
Compostos de Manganês/sangue
Compostos de Manganês/farmacocinética
Norepinefrina/metabolismo
Óxidos/sangue
Óxidos/farmacocinética
Ratos Sprague-Dawley
Serotonina/metabolismo
Taurina/metabolismo
Ácido gama-Aminobutírico/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Chlorides); 0 (Manganese Compounds); 0 (Oxides); 1EQV5MLY3D (Taurine); 333DO1RDJY (Serotonin); 3KX376GY7L (Glutamic Acid); 42Z2K6ZL8P (Manganese); 56-12-2 (gamma-Aminobutyric Acid); 64J2OA7MH3 (manganese oxide); EC 3.1.1.7 (Acetylcholinesterase); QQE170PANO (manganese chloride); VTD58H1Z2X (Dopamine); X4W3ENH1CV (Norepinephrine)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180302
[Lr] Data última revisão:
180302
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170503
[St] Status:MEDLINE
[do] DOI:10.1177/1091581817704378


  2 / 21832 MEDLINE  
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[PMID]:29308487
[Au] Autor:Barwinska-Sendra A; Baslé A; Waldron KJ; Un S
[Ad] Endereço:Institute for Cell and Molecular Biosciences, Newcastle University, Newcastle upon Tyne, NE2 4HH, UK. kevin.waldron@newcastle.ac.uk.
[Ti] Título:A charge polarization model for the metal-specific activity of superoxide dismutases.
[So] Source:Phys Chem Chem Phys;20(4):2363-2372, 2018 Jan 24.
[Is] ISSN:1463-9084
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:The pathogenicity of Staphylococcus aureus is enhanced by having two superoxide dismutases (SODs): a Mn-specific SOD and another that can use either Mn or Fe. Using 94 GHz electron-nuclear double resonance (ENDOR) and electron double resonance detected (ELDOR)-NMR we show that, despite their different metal-specificities, their structural and electronic similarities extend down to their active-site H- and N-Mn(ii) hyperfine interactions. However these interactions, and hence the positions of these nuclei, are different in the inactive Mn-reconstituted Escherichia coli Fe-specific SOD. Density functional theory modelling attributes this to a different angular position of the E. coli H171 ligand. This likely disrupts the Mn-H171-E170' triad causing a shift in charge and in metal redox potential, leading to the loss of activity. This is supported by the correlated differences in the Mn(ii) zero-field interactions of the three SOD types and suggests that the triad is important for determining metal specific activity.
[Mh] Termos MeSH primário: Proteínas de Bactérias/metabolismo
Manganês/química
Staphylococcus aureus/enzimologia
Superóxido Dismutase/metabolismo
[Mh] Termos MeSH secundário: Proteínas de Bactérias/química
Proteínas de Bactérias/genética
Sítios de Ligação
Domínio Catalítico
Cristalografia por Raios X
Espectroscopia de Ressonância de Spin Eletrônica
Escherichia coli/metabolismo
Mutagênese Sítio-Dirigida
Ressonância Magnética Nuclear Biomolecular
Oxirredução
Teoria Quântica
Proteínas Recombinantes/biossíntese
Proteínas Recombinantes/química
Proteínas Recombinantes/genética
Superóxido Dismutase/química
Superóxido Dismutase/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Bacterial Proteins); 0 (Recombinant Proteins); 42Z2K6ZL8P (Manganese); EC 1.15.1.1 (Superoxide Dismutase)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180226
[Lr] Data última revisão:
180226
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180109
[St] Status:MEDLINE
[do] DOI:10.1039/c7cp06829h


  3 / 21832 MEDLINE  
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[PMID]:29324899
[Au] Autor:Kisidayová S; Pristas P; Zimovcáková M; Blanár Wencelová M; Homol'ová L; Mihaliková K; Cobanová K; Gresáková L; Váradyová Z
[Ad] Endereço:Institute of Animal Physiology, Slovak Academy of Sciences, Kosice, Slovakia.
[Ti] Título:The effects of high dose of two manganese supplements (organic and inorganic) on the rumen microbial ecosystem.
[So] Source:PLoS One;13(1):e0191158, 2018.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Little is known about the effects of the high dose and types of manganese supplements on rumen environment at manganese intake level close above the limit of 150 mg/kg of dry feed matter. The effects of high dose of two manganese supplements (organic and inorganic) on rumen microbial ecosystem after four months of treatment of 18 lambs divided into three treatment groups were studied. We examined the enzyme activities (α-amylase, xylanase, and carboxymethyl cellulase), total and differential microscopic counts of rumen ciliates, total microscopic counts of bacteria, and fingerprinting pattern of the eubacterial and ciliates population analyzed by PCR-DGGE. Lambs were fed a basal diet with a basal Mn content (34.3 mg/kg dry matter; control) and supplemented either with inorganic manganous sulfate or organic Mn-chelate hydrate (daily 182.7, 184 mg/kg dry matter of feed, respectively). Basal diet, offered twice daily, consisted of ground barley and hay (268 and 732 g/kg dry matter per animal and day). The rumens of the lambs harbored ciliates of the genera of Entodinium, Epidinium, Diplodinium, Eudiplodinium, Dasytricha, and Isotricha. No significant differences between treatment groups were observed in the total ciliate number, the number of ciliates at the genus level, as well as the total number of bacteria. Organic Mn did decrease the species richness and diversity of the eubacterial population examined by PCR-DGGE. No effects of type of Mn supplement on the enzyme activities were observed. In comparison to the control, α-amylase specific activities were decreased and carboxymethyl-cellulase specific activities were increased by the Mn supplements. Xylanase activities were not influenced. In conclusion, our results suggested that the intake of tested inorganic and organic manganese supplements in excess may affect the specific groups of eubacteria. More studies on intake of Mn supplements at a level close to the limit can reveal if the changes in microbial population impact remarkably the other rumen enzymatic activities.
[Mh] Termos MeSH primário: Ecossistema
Manganês/administração & dosagem
Microbiota
Rúmen/microbiologia
[Mh] Termos MeSH secundário: Ração Animal
Animais
Eletroforese em Gel de Poliacrilamida
Reação em Cadeia da Polimerase
Rúmen/metabolismo
Ovinos
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
42Z2K6ZL8P (Manganese)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180223
[Lr] Data última revisão:
180223
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180112
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0191158


  4 / 21832 MEDLINE  
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[PMID]:29205667
[Au] Autor:Wang L; Fu H; Liu B; Liu X; Chen W; Yu X
[Ad] Endereço:Department of Developmental and Behavioral Pediatrics, Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine, Ministry of Education Shanghai Key Laboratory of Children's Environmental Health, Shanghai 200127, China, Shanghai, 200127, China.
[Ti] Título:The effect of postnatal manganese exposure on the NMDA receptor signaling pathway in rat hippocampus.
[So] Source:J Biochem Mol Toxicol;31(12), 2017 Dec.
[Is] ISSN:1099-0461
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Overexposure to manganese (Mn) is associated with neurological disorders in children. Evidence indicated that N-methyl-d-aspartate (NMDA) receptor signaling pathway was critical for neurobehavioral function. However, whether NMDA receptor signaling pathway contributes to Mn-induced neurotoxicity remains unknown. In this study, newborn Sprague-Dawley rats were randomly assigned to four groups exposed to 0, 10, 20, and 30 mg/kg of Mn by intraperitoneal injection (n = 10/group: five males and five females). After 3 weeks of Mn exposure, messenger RNA (mRNA) and protein expression of NMDA receptor subunits (NR1, NR2A, and NR2B), cAMP-response element binding protein (CREB), and brain-derived neurotrophic factor (BDNF) in hippocampus were measured by real-time quantitative RT-PCR and Western blot. In Mn-exposed rats, decreased mRNA and protein expression of NR1, NR2A, and NR2B, CREB, and BDNF was observed. The results imply that downregulated NMDA receptor signaling pathway may be of vital importance in the neuropathological process of Mn-induced neurotoxicity.
[Mh] Termos MeSH primário: Hipocampo/metabolismo
Manganês/toxicidade
Receptores de N-Metil-D-Aspartato/metabolismo
[Mh] Termos MeSH secundário: Animais
Animais Recém-Nascidos
Fator Neurotrófico Derivado do Encéfalo/genética
Fator Neurotrófico Derivado do Encéfalo/metabolismo
Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/genética
Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/metabolismo
Feminino
Expressão Gênica/efeitos dos fármacos
Hipocampo/efeitos dos fármacos
Masculino
Ratos Sprague-Dawley
Receptores de N-Metil-D-Aspartato/genética
Transdução de Sinais
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Brain-Derived Neurotrophic Factor); 0 (Cyclic AMP Response Element-Binding Protein); 0 (Receptors, N-Methyl-D-Aspartate); 42Z2K6ZL8P (Manganese)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180222
[Lr] Data última revisão:
180222
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171206
[St] Status:MEDLINE
[do] DOI:10.1002/jbt.21969


  5 / 21832 MEDLINE  
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[PMID]:29289693
[Au] Autor:Wang TY; Ma Z; Wang C; Liu C; Yan DY; Deng Y; Liu W; Xu ZF; Xu B
[Ad] Endereço:Department of Environmental Health, School of Public Health, China Medical University, People's Republic of China.
[Ti] Título:Manganese-induced alpha-synuclein overexpression impairs synaptic vesicle fusion by disrupting the Rab3 cycle in primary cultured neurons.
[So] Source:Toxicol Lett;285:34-42, 2018 Mar 15.
[Is] ISSN:1879-3169
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:Overexposure to Manganese (Mn) has been known to disrupt neurotransmitter release in the brain. However, the underlying mechanisms of Mn exposure on neurotransmitter vesicle release are still unclear. The current study investigated whether Mn-induced alpha-synuclein protein overexpression could disrupt the Rab3 cycle leading to synaptic vesicle fusion dysfunction. After the neurons were exposed to Mn (100 µM) for 0, 6, 12, 24 h, [Ca ] , alpha-synuclein and Rab3A-GTP protein expression increased gradually. However, the interaction of synaptotagmin/Rab3-GAP and Rab3A-GTP/Rab3-GAP decreased significantly in response to Mn treatment for 12-24 h. Remarkably, the treatment with Mn caused an increase in the interaction of alpha-synuclein/Rab3A-GTP. To further validate that Mn-induced alpha-synuclein disrupted the proteins interactions of Rab3A-GTP/Rab3-GAP, the lentivirus vector of alpha-synuclein/negative shRNA was transfected in primary cultured neurons to knockdown the expression of alpha-synuclein. Our results showed that the interaction of Rab3A-GTP/Rab3-GAP in alpha-synuclein knockdown neurons treated with Mn for 24 h had a significant recovery. These results suggested that Mn-induced alpha-synuclein protein overexpression, which bound to Rab3A-GTP and inhibited the GTP hydrolysis of Rab3 protein, disrupted the Rab3 cycle leading to synaptic vesicle fusion dysfunction.
[Mh] Termos MeSH primário: Manganês/toxicidade
Fusão de Membrana/efeitos dos fármacos
Neurônios/efeitos dos fármacos
Vesículas Sinápticas/efeitos dos fármacos
alfa-Sinucleína/metabolismo
Proteínas rab3 de Ligação ao GTP/metabolismo
[Mh] Termos MeSH secundário: Animais
Animais Recém-Nascidos
Sobrevivência Celular/efeitos dos fármacos
Células Cultivadas
Técnicas de Silenciamento de Genes
Neurônios/metabolismo
Cultura Primária de Células
Ratos Wistar
Vesículas Sinápticas/metabolismo
alfa-Sinucleína/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (alpha-Synuclein); 42Z2K6ZL8P (Manganese); EC 3.6.5.2 (rab3 GTP-Binding Proteins)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180219
[Lr] Data última revisão:
180219
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180101
[St] Status:MEDLINE


  6 / 21832 MEDLINE  
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[PMID]:28471522
[Au] Autor:Chen SY; Li Q; Liu XG; Wu JQ; Zhang SS; Wang H
[Ad] Endereço:School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, 510006, P. R. China.
[Ti] Título:Polycyclization Enabled by Relay Catalysis: One-Pot Manganese-Catalyzed C-H Allylation and Silver-Catalyzed Povarov Reaction.
[So] Source:ChemSusChem;10(11):2360-2364, 2017 06 09.
[Is] ISSN:1864-564X
[Cp] País de publicação:Germany
[La] Idioma:eng
[Ab] Resumo:In this study, a Mn /Ag -based relay catalysis process is described for the one-pot synthesis of polycyclic products by a formal [3+2] and [4+2] cycloaddition reaction cascade. A manganese(I) complex catalyzed the first example of directed C-H allylation with allenes, setting the stage for an in situ Povarov cyclization catalyzed by silver(I). The reaction proceeds with high bond-forming efficiency (three C-C bonds), broad substrate scope, high regio- and stereoselectivity, and 100 % atom economy.
[Mh] Termos MeSH primário: Compostos Alílicos/química
Reação de Cicloadição/métodos
Manganês/química
Prata/química
[Mh] Termos MeSH secundário: Catálise
Ciclização
Estereoisomerismo
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Allyl Compounds); 3M4G523W1G (Silver); 42Z2K6ZL8P (Manganese)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:180117
[Lr] Data última revisão:
180117
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170505
[St] Status:MEDLINE
[do] DOI:10.1002/cssc.201700452


  7 / 21832 MEDLINE  
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[PMID]:28466599
[Au] Autor:Barwe S; Andronescu C; Masa J; Ventosa E; Klink S; Genç A; Arbiol J; Schuhmann W
[Ad] Endereço:Analytical Chemistry, Center for Electrochemical Sciences (CES), Ruhr-Universität Bochum, 44780, Bochum, Germany.
[Ti] Título:Polybenzoxazine-Derived N-doped Carbon as Matrix for Powder-Based Electrocatalysts.
[So] Source:ChemSusChem;10(12):2653-2659, 2017 06 22.
[Is] ISSN:1864-564X
[Cp] País de publicação:Germany
[La] Idioma:eng
[Ab] Resumo:In addition to catalytic activity, intrinsic stability, tight immobilization on a suitable electrode surface, and sufficient electronic conductivity are fundamental prerequisites for the long-term operation of particle- and especially powder-based electrocatalysts. We present a novel approach to concurrently address these challenges by using the unique properties of polybenzoxazine (pBO) polymers, namely near-zero shrinkage and high residual-char yield even after pyrolysis at high temperatures. Pyrolysis of a nanocubic prussian blue analogue precursor (K Mn [Co(CN) ] ⋅n H O) embedded in a bisphenol A and aniline-based pBO led to the formation of a N-doped carbon matrix modified with Mn Co O nanocubes. The obtained electrocatalyst exhibits high efficiency toward the oxygen evolution reaction (OER) and more importantly a stable performance for at least 65 h.
[Mh] Termos MeSH primário: Benzoxazinas/química
Carbono/química
Nitrogênio/química
Polímeros/química
[Mh] Termos MeSH secundário: Catálise
Cobalto/química
Eletroquímica
Manganês/química
Nanoestruturas/química
Pós
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Benzoxazines); 0 (Polymers); 0 (Powders); 3G0H8C9362 (Cobalt); 42Z2K6ZL8P (Manganese); 7440-44-0 (Carbon); N762921K75 (Nitrogen)
[Em] Mês de entrada:1707
[Cu] Atualização por classe:180118
[Lr] Data última revisão:
180118
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170504
[St] Status:MEDLINE
[do] DOI:10.1002/cssc.201700593


  8 / 21832 MEDLINE  
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[PMID]:28461400
[Au] Autor:Eroglu S; Giehl RFH; Meier B; Takahashi M; Terada Y; Ignatyev K; Andresen E; Küpper H; Peiter E; von Wirén N
[Ad] Endereço:Molecular Plant Nutrition, Leibniz-Institute for Plant Genetics and Crop Plant Research, D-06466 Gatersleben, Germany.
[Ti] Título:Metal Tolerance Protein 8 Mediates Manganese Homeostasis and Iron Reallocation during Seed Development and Germination.
[So] Source:Plant Physiol;174(3):1633-1647, 2017 Jul.
[Is] ISSN:1532-2548
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Metal accumulation in seeds is a prerequisite for germination and establishment of plants but also for micronutrient delivery to humans. To investigate metal transport processes and their interactions in seeds, we focused on METAL TOLERANCE PROTEIN8 (MTP8), a tonoplast transporter of the manganese (Mn) subclade of cation diffusion facilitators, which in Arabidopsis ( ) is expressed in embryos of seeds. The x-ray fluorescence imaging showed that expression of MTP8 was responsible for Mn localization in subepidermal cells on the abaxial side of the cotyledons and in cortical cells of the hypocotyl. Accordingly, under low Mn availability, MTP8 increased seed stores of Mn, required for efficient seed germination. In mutant embryos lacking expression of ( ), MTP8 built up iron (Fe) hotspots in -expressing cells types, suggesting that MTP8 transports Fe in addition to Mn. In double mutant seeds, Mn and Fe were distributed in all cell types of the embryo. An Fe transport function of MTP8 was confirmed by its ability to complement Fe hypersensitivity of a yeast mutant defective in vacuolar Fe transport. Imbibing mutant seeds in the presence of Mn or subjecting seeds to wet-dry cycles showed that MTP8 conferred Mn tolerance. During germination, MTP8 promoted reallocation of Fe from the vasculature. These results indicate that cell type-specific accumulation of Mn and Fe in seeds depends on MTP8 and that this transporter plays an important role in the generation of seed metal stores as well as for metal homeostasis and germination efficiency under challenging environmental conditions.
[Mh] Termos MeSH primário: Proteínas de Arabidopsis/metabolismo
Arabidopsis/embriologia
Arabidopsis/metabolismo
Proteínas de Transporte de Cátions/metabolismo
Germinação
Homeostase
Ferro/metabolismo
Manganês/metabolismo
Sementes/embriologia
[Mh] Termos MeSH secundário: Arabidopsis/genética
Regulação da Expressão Gênica no Desenvolvimento
Regulação da Expressão Gênica de Plantas
Técnicas de Inativação de Genes
Teste de Complementação Genética
Germinação/genética
Modelos Biológicos
Mutação/genética
Regiões Promotoras Genéticas/genética
Saccharomyces cerevisiae/metabolismo
Sementes/genética
Espectrometria por Raios X
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Arabidopsis Proteins); 0 (Cation Transport Proteins); 0 (MTP8 protein, Arabidopsis); 42Z2K6ZL8P (Manganese); E1UOL152H7 (Iron)
[Em] Mês de entrada:1801
[Cu] Atualização por classe:180115
[Lr] Data última revisão:
180115
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170503
[St] Status:MEDLINE
[do] DOI:10.1104/pp.16.01646


  9 / 21832 MEDLINE  
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[PMID]:29277766
[Au] Autor:Hernroth B; Holm I; Gondikas A; Tassidis H
[Ad] Endereço:Department of Natural Science, Kristianstad University, Kristianstad, Sweden.
[Ti] Título:Manganese Inhibits Viability of Prostate Cancer Cells.
[So] Source:Anticancer Res;38(1):137-145, 2018 01.
[Is] ISSN:1791-7530
[Cp] País de publicação:Greece
[La] Idioma:eng
[Ab] Resumo:BACKGROUND/AIM: Androgen deprivation therapy is usually in the initial phase a successful treatment for prostate cancer but eventually most patients develop androgen-independent metastatic disease. This study investigated if manganese (Mn) reduces viability of prostate cancer via induction of apoptosis. MATERIALS AND METHODS: The prostate cancer cell lines PC3, DU145 and LNCaP underwent dose- and time-dependent screening of viability, analyzed by the 3-(4,5-dimethyl-thiazol-2-yl)-2,5-diphenyl-tetrazolium bromide assay. Flow cytometry was used for the cell-cycle and apoptosis analyses. Intracellular Mn concentration was measured using inductively coupled plasma-mass spectrometry. RESULTS: At Mn concentrations of 200-1000 µM, the effect on viability was most pronounced in PC3 followed by LNCaP cells. These cell lines also showed higher intracellular concentration of Mn compared to DU145. In all cell lines, Mn increased the proportion of cells arrested in the G /G phase and induced apoptosis. CONCLUSION: To our knowledge, this is the first report demonstrating Mn as a potential agent in prostate cancer therapy.
[Mh] Termos MeSH primário: Antineoplásicos/farmacologia
Manganês/farmacologia
Neoplasias da Próstata/tratamento farmacológico
[Mh] Termos MeSH secundário: Apoptose/efeitos dos fármacos
Ciclo Celular/efeitos dos fármacos
Linhagem Celular Tumoral
Sobrevivência Celular/efeitos dos fármacos
Seres Humanos
Masculino
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antineoplastic Agents); 42Z2K6ZL8P (Manganese)
[Em] Mês de entrada:1801
[Cu] Atualização por classe:180104
[Lr] Data última revisão:
180104
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171227
[St] Status:MEDLINE


  10 / 21832 MEDLINE  
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[PMID]:28461334
[Au] Autor:Hutchens S; Liu C; Jursa T; Shawlot W; Chaffee BK; Yin W; Gore AC; Aschner M; Smith DR; Mukhopadhyay S
[Ad] Endereço:From the Division of Pharmacology & Toxicology, College of Pharmacy, Institute for Cellular & Molecular Biology, and Institute for Neuroscience and.
[Ti] Título:Deficiency in the manganese efflux transporter SLC30A10 induces severe hypothyroidism in mice.
[So] Source:J Biol Chem;292(23):9760-9773, 2017 06 09.
[Is] ISSN:1083-351X
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Manganese is an essential metal that becomes toxic at elevated levels. Loss-of-function mutations in SLC30A10, a cell-surface-localized manganese efflux transporter, cause a heritable manganese metabolism disorder resulting in elevated manganese levels and parkinsonian-like movement deficits. The underlying disease mechanisms are unclear; therefore, treatment is challenging. To understand the consequences of loss of function at the organism level, we generated knock-out mice. During early development, knock-outs were indistinguishable from controls. Surprisingly, however, after weaning and compared with controls, knock-out mice failed to gain weight, were smaller, and died prematurely (by ∼6-8 weeks of age). At 6 weeks, manganese levels in the brain, blood, and liver of the knock-outs were ∼20-60-fold higher than controls. Unexpectedly, histological analyses revealed that the brain and liver of the knock-outs were largely unaffected, but their thyroid exhibited extensive alterations. Because hypothyroidism leads to growth defects and premature death in mice, we assayed for changes in thyroid and pituitary hormones. At 6 weeks and compared with controls, the knock-outs had markedly reduced thyroxine levels (∼50-80%) and profoundly increased thyroid-stimulating hormone levels (∼800-1000-fold), indicating that knock-out mice develop hypothyroidism. Importantly, a low-manganese diet produced lower tissue manganese levels in the knock-outs and rescued the phenotype, suggesting that manganese toxicity was the underlying cause. Our unanticipated discovery highlights the importance of determining the role of thyroid dysfunction in the onset and progression of manganese-induced disease and identifies knock-out mice as a new model for studying thyroid biology.
[Mh] Termos MeSH primário: Proteínas de Transporte de Cátions/deficiência
Hipotireoidismo/genética
Hipotireoidismo/metabolismo
Manganês/metabolismo
Glândula Tireoide/metabolismo
[Mh] Termos MeSH secundário: Animais
Modelos Animais de Doenças
Hipotireoidismo/patologia
Camundongos
Camundongos Knockout
Glândula Tireoide/patologia
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL
[Nm] Nome de substância:
0 (Cation Transport Proteins); 42Z2K6ZL8P (Manganese)
[Em] Mês de entrada:1706
[Cu] Atualização por classe:171228
[Lr] Data última revisão:
171228
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170503
[St] Status:MEDLINE
[do] DOI:10.1074/jbc.M117.783605



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