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Mitochondrial toxicity

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https://www.readbyqxmd.com/read/27913906/synergistic-mitotoxicity-of-chloromethanes-and-fullerene-c60-nanoaggregates-in-daphnia-magna-midgut-epithelial-cells
#1
Mariana Seke, Milica Markelic, Arian Morina, Danica Jovic, Aleksandra Korac, Dragana Milicic, Aleksandar Djordjevic
Adsorption of non-polar compounds by suspended fullerene nanoaggregates (nC60) may enhance their toxicity and affect the fate, transformation, and transport of non-polar compounds in the environment. The potential of stable fullerene nanoaggregates as contaminant carriers in aqueous systems and the influence of chloromethanes (trichloromethane and dichloromethane) were studied on the midgut epithelial cells of Daphnia magna by light and electron microscopy. The size and shape of fullerene nanoaggregates were observed and measured using dynamic light scattering, transmission electron microscopy, and low vacuum scanning electron microscopy...
December 3, 2016: Protoplasma
https://www.readbyqxmd.com/read/27913197/doxorubicin-induced-mitophagy-contributes-to-drug-resistance-in-cancer-stem-cells-from-hct8-human-colorectal-cancer-cells
#2
Chen Yan, Lan Luo, Chang-Ying Guo, Shinji Goto, Yoshishige Urata, Jiang-Hua Shao, Tao-Sheng Li
Cancer stem cells (CSCs) are known to be drug resistant. Mitophagy selectively degrades unnecessary or damaged mitochondria by autophagy during cellular stress. To investigate the potential role of mitophagy in drug resistance in CSCs, we purified CD133(+)/CD44(+) CSCs from HCT8 human colorectal cancer cells and then exposed to doxorubicin (DXR). Compared with parental cells, CSCs were more resistant to DXR treatment. Although DXR treatment enhanced autophagy levels in both cell types, the inhibition of autophagy by ATG7 silencing significantly increased the toxicity of DXR only in parental cells, not in CSCs...
November 29, 2016: Cancer Letters
https://www.readbyqxmd.com/read/27906059/a-mitochondrial-hsp70-hspa9b-is-linked-to-miltefosine-resistance-and-stress-response-in-leishmania-donovani
#3
P Vacchina, B Norris-Mullins, E S Carlson, M A Morales
BACKGROUND: Protozoan parasites of the genus Leishmania are responsible for leishmaniasis, a neglected tropical disease affecting millions worldwide. Visceral leishmaniasis (VL), caused by Leishmania donovani, is the most severe form of leishmaniasis with high rates of mortality if left untreated. Current treatments include pentavalent antimonials and amphotericin B. However, high toxicity and emergence of resistance hinder the success of these options. Miltefosine (HePC) is the first oral treatment available for leishmaniasis...
December 1, 2016: Parasites & Vectors
https://www.readbyqxmd.com/read/27905038/biological-activity-of-spirocyclic-hydroxamic-acids
#4
M E Neganova, D V Mishchenko, T P Serkova, I V Vystorop, E F Shevtsova
Iron-chelating activity of synthesized spirocyclic hydroxamic acids, their toxicity, and effects on mitochondrial function were studied using primary culture of cerebral cortical neurons from newborn rats. All tested compounds effectively chelated Fe(II) ions. Activity of spirocyclic hydroxamic acids more strictly depended on the structure their piperidine, but not imidazolidine fragment. All compounds were non-toxic for normal neuronal culture.
December 1, 2016: Bulletin of Experimental Biology and Medicine
https://www.readbyqxmd.com/read/27904736/the-biology-behind-b-cell-lymphoma-2-as-a-target-in-chronic-lymphocytic-leukemia
#5
REVIEW
Valentín Ortíz-Maldonado, Pablo Mozas, Julio Delgado
B-cell lymphoma 2 (BCL2)-type proteins are key regulators of the intrinsic or mitochondrial pathway for apoptosis. Since escape from apoptosis is one the main 'hallmarks of cancer', BCL2 inhibitors have emerged as promising therapeutic agents for diverse lymphoid malignancies, particularly chronic lymphocytic leukemia (CLL). Multiple clinical trials have shown efficacy of these agents in patients with relapsed/refractory disease with a favorable toxicity profile. Moreover, some clinical trials indicate that combination with monoclonal antibodies and other novel agents may enhance their effect...
December 2016: Therapeutic Advances in Hematology
https://www.readbyqxmd.com/read/27904582/the-role-of-peroxisome-proliferator-activated-receptor-coactivator-1-gene-in-skin-aging
#6
REVIEW
Shahrzad Aghaei, Mohammad Ali Nilforoushzadeh, Maryam Aghaei
Skin aging is a continuous process that exhibits fine and deep wrinkles, thin and transparent skin, loss of underlying fat, dry skin and itch, following decreased collagen and elastin synthesis. Both extrinsic and intrinsic agents are considered in the pathogenesis on skin aging. Extrinsic factors such as sun exposure, windy and dry weather, nutrition, and lifestyle may induce premature aging, toxic-free radicals, and reactive oxygen species due to decreasing normal function of mitochondria which play the major intrinsic factors in premature skin aging...
2016: Journal of Research in Medical Sciences: the Official Journal of Isfahan University of Medical Sciences
https://www.readbyqxmd.com/read/27902770/mitochondrial-targeted-decyl-triphenylphosphonium-enhances-2-deoxy-d-glucose-mediated-oxidative-stress-and-clonogenic-killing-of-multiple-myeloma-cells
#7
Jeanine Schibler, Ann M Tomanek-Chalkley, Jessica L Reedy, Fenghuang Zhan, Douglas R Spitz, Michael K Schultz, Apollina Goel
Therapeutic advances have markedly prolonged overall survival in multiple myeloma (MM) but the disease currently remains incurable. In a panel of MM cell lines (MM.1S, OPM-2, H929, and U266), using CD138 immunophenotyping, side population staining, and stem cell-related gene expression, we demonstrate the presence of stem-like tumor cells. Hypoxic culture conditions further increased CD138low stem-like cells with upregulated expression of OCT4 and NANOG. Compared to MM cells, these stem-like cells maintained lower steady-state pro-oxidant levels with increased uptake of the fluorescent deoxyglucose analog...
2016: PloS One
https://www.readbyqxmd.com/read/27901621/perfluorooctanoic-acid-induces-mitochondrial-dysfunction-in-mc3t3-e1-osteoblast-cells
#8
Eun Mi Choi, Kwang Sik Suh, Sang Youl Rhee, Seungjoon Oh, Jeong-Taek Woo, Sung Woon Kim, Young Seol Kim, Youngmi Kim Pak, Suk Chon
Perfluorooctanoic acid (PFOA), a stable organic perfluorinated compound, is an emerging persistent organic pollutant, found widely in human and wildlife populations. Recent evidence suggests that exposure to environmental toxicants can be associated with higher risks of osteoporosis and fractures. We studied the cellular toxicology of PFOA in MC3T3-E1osteoblast cells. To examine the effect of PFOA, we measured cell viability, reactive oxygen species (ROS), mitochondrial superoxide, and mitochondrial parameters including adenosine triphosphate (ATP) level, mitochondrial membrane potential (MMP), cardiolipin content, and cytochrome c release in MC3T3-E1 cells...
November 30, 2016: Journal of Environmental Science and Health. Part A, Toxic/hazardous Substances & Environmental Engineering
https://www.readbyqxmd.com/read/27897980/protective-effects-of-%C3%AE-tocopherol-%C3%AE-tocopherol-and-oleic-acid-three-compounds-of-olive-oils-and-no-effect-of-trolox-on-7-ketocholesterol-induced-mitochondrial-and-peroxisomal-dysfunction-in-microglial-bv-2-cells
#9
Meryam Debbabi, Thomas Nury, Amira Zarrouk, Nadia Mekahli, Maryem Bezine, Randa Sghaier, Stéphane Grégoire, Lucy Martine, Philippe Durand, Emmanuelle Camus, Anne Vejux, Aymen Jabrane, Lionel Bretillon, Michel Prost, Thibault Moreau, Sofien Ben Ammou, Mohamed Hammami, Gérard Lizard
Lipid peroxidation products, such as 7-ketocholesterol (7KC), may be increased in the body fluids and tissues of patients with neurodegenerative diseases and trigger microglial dysfunction involved in neurodegeneration. It is therefore important to identify synthetic and natural molecules able to impair the toxic effects of 7KC. We determined the impact of 7KC on murine microglial BV-2 cells, especially its ability to trigger mitochondrial and peroxisomal dysfunction, and evaluated the protective effects of α- and γ-tocopherol, Trolox, and oleic acid (OA)...
November 25, 2016: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/27897111/aggressive-antioxidant-reductive-stress-impairs-brain-endothelial-cell-angiogenesis-and-blood-brain-barrier-function
#10
Shireen Mentor, David Fisher
Oxidative stress in the brain microvasculature is a common characteristic in models of cerebrovascular disease. Considering the effects of reactive oxygen species activity in vascular-derived insults, it is naturally prudent to hypothesize those interventions inhibiting reactive oxygen species activity, such as antioxidant supplementation, may be beneficial for cerebrovascular disease. Hyper doses of antioxidant supplements, and foods with high antioxidant concentrations, are commonly used as an ongoing remedial and 'over-the-counter' treatments for most seasonal ailments...
November 29, 2016: Current Neurovascular Research
https://www.readbyqxmd.com/read/27896021/lithocholic-acid-induces-endoplasmic-reticulum-stress-autophagy-and-mitochondrial-dysfunction-in-human-prostate-cancer-cells
#11
Ahmed A Gafar, Hossam M Draz, Alexander A Goldberg, Mohamed A Bashandy, Sayed Bakry, Mahmoud A Khalifa, Walid AbuShair, Vladimir I Titorenko, J Thomas Sanderson
Lithocholic acid (LCA) is a secondary bile acid that is selectively toxic to human neuroblastoma, breast and prostate cancer cells, whilst sparing normal cells. We previously reported that LCA inhibited cell viability and proliferation and induced apoptosis and necrosis of androgen-dependent LNCaP and androgen-independent PC-3 human prostate cancer cells. In the present study, we investigated the roles of endoplasmic reticulum (ER) stress, autophagy and mitochondrial dysfunction in the toxicity of LCA in PC-3 and autophagy deficient, androgen-independent DU-145 cells...
2016: PeerJ
https://www.readbyqxmd.com/read/27895312/activation-of-endoplasmic-reticulum-stress-and-the-extrinsic-apoptotic-pathway-in-human-lung-cancer-cells-by-the-new-synthetic-flavonoid-lz-205
#12
Yi Zhang, Xuefen Xu, Wei Li, Hanchi Miao, Shaoliang Huang, Yuxin Zhou, Yang Sun, Zhiyu Li, Qinglong Guo, Li Zhao
It has been shown that flavonoids have anti-tumor activity. In this study, LZ-205, a newly synthesized flavonoid, was found to be effective in inducing apoptosis in human lung cancer cells in vivo and in vitro. Mechanistically, LZ-205 triggers reactive oxygen species (ROS)-induced endoplasmic reticulum (ER) stress and unfolded protein response, which could be reversed by silencing CHOP, a mediator of the ER stress-associated apoptosis. In addition, LZ-205-induced apoptosis is accompanied by the activation of both the mitochondrial apoptotic and extrinsic pathways, followed by decreased mitochondrial membrane potential (ΔΨm) and the alteration of the expression of mitochondria-related pro- and anti-apoptotic proteins...
November 24, 2016: Oncotarget
https://www.readbyqxmd.com/read/27894362/the-trypanosome-alternative-oxidase-a-potential-drug-target
#13
Stefanie K Menzies, Lindsay B Tulloch, Gordon J Florence, Terry K Smith
New drugs against Trypanosoma brucei, the causative agent of Human African Trypanosomiasis, are urgently needed to replace the highly toxic and largely ineffective therapies currently used. The trypanosome alternative oxidase (TAO) is an essential and unique mitochondrial protein in these parasites and is absent from mammalian mitochondria, making it an attractive drug target. The structure and function of the protein are now well characterized, with several inhibitors reported in the literature, which show potential as clinical drug candidates...
November 29, 2016: Parasitology
https://www.readbyqxmd.com/read/27893995/combined-effects-of-cadmium-temperature-and-hypoxia-reoxygenation-on-mitochondrial-function-in-rainbow-trout-oncorhynchus-mykiss
#14
John O Onukwufor, Don Stevens, Collins Kamunde
Although aquatic organisms face multiple environmental stressors that may interact to alter adverse outcomes, our knowledge of stressor-stressor interaction on cellular function is limited. We investigated the combined effects of cadmium (Cd), hypoxia-reoxygenation (H-R) and temperature on mitochondrial function. Liver mitochondria from juvenile rainbow trout were exposed to Cd (0-20μM) and H-R (0 and 5min) at 5, 13 and 25°C followed by measurements of mitochondrial Cd load, volume, complex І active (A)↔deactive (D) transition, membrane potential, ROS release and ultrastructural changes...
November 18, 2016: Aquatic Toxicology
https://www.readbyqxmd.com/read/27889531/sirt1-protects-cardiac-cells-against-apoptosis-induced-by-zearalenone-or-its-metabolites-%C3%AE-and-%C3%AE-zearalenol-through-an-autophagy-dependent-pathway
#15
Intidhar Ben Salem, Manel Boussabbeh, Julie Pires Da Silva, Arnaud Guilbert, Hassen Bacha, Salwa Abid-Essefi, Christophe Lemaire
Zearalenone (ZEN) is a non-steroidal estrogenic mycotoxin produced by several species of Fusarium in cereals and agricultural products. The major ZEN metabolites are α-zearalenol (α-ZOL) and β-zearalenol (β-ZOL). In the present study, we investigated the underlying mechanism of the toxicity induced by ZEN, α-ZOL and β-ZOL in cardiac cells (H9c2). We show that treatment with ZEN or its metabolites induces the activation of the mitochondrial pathway of apoptosis as characterized by an increase in ROS generation, a loss of mitochondrial transmembrane potential (ΔΨm) and an activation of caspases...
November 23, 2016: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/27885834/presence-of-an-immune-system-increases-anti-tumor-effect-of-ag-nanoparticle-treated-mice
#16
Bella B Manshian, Julio Jimenez, Uwe Himmelreich, Stefaan J Soenen
To date, most nanomedical studies rely on the use of immune-deficient mice in which the contribution of the immune system on the applied therapy is ignored. Here, the degradation of silver nanoparticles (Ag NPs) is exploited as a means to treat subcutaneous tumor models in mice. To investigate the impact of the immune system, the same tumor cell type (KLN 205 murine squamous cell carcinoma) is used in a xenograft model in NOD SCIDγ immune-deficient mice and as a syngeneic model in immune-competent DBA/2 mice...
November 25, 2016: Advanced Healthcare Materials
https://www.readbyqxmd.com/read/27883213/oxidative-stress-and-amyloid-toxicity-insights-from-yeast
#17
Mauro B França, Karina C Lima, Elis C A Eleutherio
Alzheimer's disease is the most common neurodegenerative disorder. One of the factors that promotes neurodegeneration is the accumulation of senile plaques formed by Aβ peptide. In this paper it was analyzed if oxidative stress is cause or consequence of amyloid cascade and the role of antioxidant defense system in this process, using S. cerevisiae (with a multicopy plasmid containing the Aβ1-42 sequence) as experimental model. Cells grown on glycerol were more tolerant than when grown on glucose, strengthening the role of the antioxidant defense system against Aβ accumulation...
November 24, 2016: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/27882077/potential-protective-effects-of-autophagy-activated-in-mpp-treated-astrocytes
#18
Cunzhou Shen, Wenbiao Xian, Hongyan Zhou, Ling Chen, Zhong Pei
Astrocytes, which have various important functions, have previously been associated with Parkinsons disease (PD), particularly in 1-methyl-4-phenylpyridinium (MPP+) and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) models of PD. MPP+ is the toxic metabolite of MPTP and is generated by the enzymatic activity of monoamine oxidase B, which is predominantly located in astrocytes. MPP+ acts as a mitochondrial complex I inhibitor. Autophagy is an evolutionarily conserved self-digestion pathway in eukaryotic cells, which occurs in response to various types of stress, including starvation and oxidative stress...
November 2016: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/27881717/localization-of-1-deoxysphingolipids-to-mitochondria-induces-mitochondrial-dysfunction
#19
Irina Alecu, Andrea Tedeschi, Natascha Behler, Klaus Wunderling, Christian Lamberz, Mario A R Lauterbach, Anne Gaebler, Daniela Ernst, Paul P Van Veldhoven, Ashraf Al-Amoudi, Eicke Latz, Alaa Othman, Lars Kuerschner, Thorsten Hornemann, Frank Bradke, Christoph Thiele, Anke Penno
1-Deoxysphingolipids (deoxySLs) are atypical sphingolipids that are elevated in the plasma of patients with type 2 diabetes and hereditary sensory and autonomic neuropathy type 1 (HSAN1). Clinically, diabetic neuropathy and HSAN1 are very similar, suggesting the involvement of deoxySLs in the pathology of both diseases. However, very little is known about the biology of these lipids and the underlying pathomechanism. We synthesized an alkyne analogue of 1-deoxysphinganine (doxSA), the metabolic precursor of all deoxySLs, to trace the metabolism and localization of deoxySLs...
November 23, 2016: Journal of Lipid Research
https://www.readbyqxmd.com/read/27879683/synthesis-and-evaluation-of-new-benzodioxole-based-thiosemicarbazone-derivatives-as-potential-antitumor-agents
#20
Mehlika Dilek Altıntop, Halide Edip Temel, Belgin Sever, Gülşen Akalın Çiftçi, Zafer Asım Kaplancıklı
New benzodioxole-based thiosemicarbazone derivatives were synthesized and evaluated for their cytotoxic effects on A549 human lung adenocarcinoma, C6 rat glioma and NIH/3T3 mouse embryonic fibroblast cells. In order to examine the correlation between anticancer activity and cholinesterases, the compounds were evaluated for their inhibitory effects on AChE and BuChE. The most effective anticancer agents were investigated for their effects on DNA synthesis, apoptosis and mitochondrial membrane potential. 4-(1,3-Benzodioxol-5-yl)-1-([1,1'-biphenyl]-4-ylmethylene)thiosemicarbazide (5) was identified as the most promising anticancer agent against C6 and A549 cell lines due to its inhibitory effects on C6 and A549 cells and low toxicity to NIH/3T3 cells...
November 22, 2016: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
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