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https://www.readbyqxmd.com/read/29151169/parkinson-s-disease-experimental-models-and-reality
#1
REVIEW
Peizhou Jiang, Dennis W Dickson
Parkinson's disease (PD) is a chronic, progressive movement disorder of adults and the second most common neurodegenerative disease after Alzheimer's disease. Neuropathologic diagnosis of PD requires moderate-to-marked neuronal loss in the ventrolateral substantia nigra pars compacta and α-synuclein (αS) Lewy body pathology. Nigrostriatal dopaminergic neurodegeneration correlates with the Parkinsonian motor features, but involvement of other peripheral and central nervous system regions leads to a wide range of non-motor features...
November 18, 2017: Acta Neuropathologica
https://www.readbyqxmd.com/read/29149835/forkhead-transcription-factors-formulating-a-foxo-target-for-cognitive-loss
#2
Kenneth Maiese
BACKGROUND: With almost 47 million individuals worldwide suffering from some aspect of dementia, it is clear that cognitive loss impacts a significant proportion of the global population. Unfortunately, definitive treatments to resolve or prevent the onset of cognitive loss are limited. In most cases such care is currently non-existent prompting the need for novel treatment strategies. METHODS: Mammalian forkhead transcription factors of the O class (FoxO) are one such avenue of investigation that offer an exciting potential to bring new treatments forward for disorders that involve cognitive loss...
November 15, 2017: Current Neurovascular Research
https://www.readbyqxmd.com/read/29149759/dusp1-alleviates-cardiac-ischemia-reperfusion-injury-by-suppressing-the-mff-required-mitochondrial-fission-and-bnip3-related-mitophagy-via-the-jnk-pathways
#3
Qinhua Jin, Ruibing Li, Nan Hu, Ting Xin, Pingjun Zhu, Shunying Hu, Sai Ma, Hong Zhu, Jun Ren, Hao Zhou
Mitochondrial fission and selective mitochondrial autophagy (mitophagy) form an essential axis of mitochondrial quality control that plays a critical role in the development of cardiac ischemia-reperfusion (IR) injury. However, the precise upstream molecular mechanism of fission/mitophagy remains unclear. Dual-specificity protein phosphatase1 (DUSP1) regulates cardiac metabolism, but its physiological contribution in the reperfused heart, particularly its influence on mitochondrial homeostasis, is unknown. Here, we demonstrated that cardiac DUSP1 was downregulated following acute cardiac IR injury...
November 6, 2017: Redox Biology
https://www.readbyqxmd.com/read/29149599/autophagosomal-content-profiling-reveals-an-lc3c-dependent-piecemeal-mitophagy-pathway
#4
François Le Guerroué, Franziska Eck, Jennifer Jung, Tatjana Starzetz, Michel Mittelbronn, Manuel Kaulich, Christian Behrends
Autophagy allows the degradation of cytosolic endogenous and exogenous material in the lysosome. Substrates are engulfed by double-membrane vesicles, coined autophagosomes, which subsequently fuse with lysosomes. Depending on the involvement of specific receptor proteins, autophagy occurs in a selective or nonselective manner. While this process is well understood at the level of bulky cargo such as mitochondria and bacteria, we know very little about individual proteins and protein complexes that are engulfed and degraded by autophagy...
November 16, 2017: Molecular Cell
https://www.readbyqxmd.com/read/29148970/autophagic-cell-death-is-dependent-on-lysosomal-membrane-permeability-through-bax-and-bak
#5
Jason Karch, Tobias G Schips, Bryan D Maliken, Matthew J Brody, Michelle A Sargent, Onur Kanisciak, Jeffery D Molkentin
Cells deficient in the pro-death Bcl-2 family members Bax and Bak are known to be resistant to apoptotic cell death, and in a previous eLIFE paper, Karch et al., 2013 showed that these 2 effectors are also needed for mitochondrial-dependent cellular necrosis. Here we show that mouse embryonic fibroblasts deficient in Bax/Bak1 are resistant to the third major form of cell death associated with autophagy through a mechanism involving lysosome permeability. Indeed, specifically targeting Bax only to the lysosome restores autophagic cell death in Bax/Bak1 null cells...
November 17, 2017: ELife
https://www.readbyqxmd.com/read/29148034/role-of-p62-sqstm1-beyond-autophagy-a-lesson-learned-from-drug-induced-toxicity-in-vitro
#6
Fernando Alegre, Ángela B Moragrega, Miriam Polo, Alberto Marti-Rodrigo, Juan V Esplugues, Ana Blas-Garcia, Nadezda Apostolova
BACKGROUND AND PURPOSE: SQSTM1/p62 is a multifunctional, stress-induced, scaffold protein involved in multiple cellular processes including autophagic clearance, regulation of inflammatory responses and redox homeostasis. Alterations in its function have been associated with a long list of human pathologies such as neurodegenerative, metabolic and bone diseases (down-regulation), and cancerogenesis (up-regulation). However, its role in the off-target effects of clinically used drugs is still not understood...
November 17, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/29142208/transient-increases-in-intracellular-calcium-and-reactive-oxygen-species-levels-in-tcam-2-cells-exposed-to-microgravity
#7
C Morabito, S Guarnieri, A Catizone, C Schiraldi, G Ricci, M A Mariggiò
The effects of microgravity on functions of the human body are well described, including alterations in the male and female reproductive systems. In the present study, TCam-2 cells, which are considered a good model of mitotically active male germ cells, were used to investigate intracellular signalling and cell metabolism during exposure to simulated microgravity, a condition that affects cell shape and cytoskeletal architecture. After a 24 hour exposure to simulated microgravity, TCam-2 cells showed 1) a decreased proliferation rate and a delay in cell cycle progression, 2) increased anaerobic metabolism accompanied by increased levels of intracellular Ca(2+), reactive oxygen species and superoxide anion and modifications in mitochondrial morphology...
November 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29141573/liver-protective-effects-of-extra-virgin-olive-oil-interaction-between-its-chemical-composition-and-the-cell-signaling-pathways-involved-in-protection
#8
Sandra A Soto-Alarcon, Rodrigo Valenzuela, Alfonso Valenzuela, Luis A Videla
BACKGROUND AND OBJECTIVE: The liver is an organ susceptible to a multitude of injuries that causes liver damage, like steatosis, non-alcoholic steatohepatitis, cirrhosis, hepatocellular carcinoma, and ischemia-reperfusion injury. Extra virgin olive oil (EVOO), presents several protective effects on the liver, reducing hepatic steatosis, hepatocyte ballooning, fibrogenesis, preventing lipid peroxidation, among other effects. Due to its high levels of monounsaturated fatty acids, mainly oleic acid and phenolic compounds, such as hydroxytyrosol and oleuropein, EVOO is able to participate in the activation of different signaling pathways in the hepatocytes involved in the prevention of inflammation, oxidative stress, endoplasmic reticulum stress, mitochondrial dysfunction, and insulin resistance, allowing the prevention or resolution of liver damage...
November 14, 2017: Endocrine, Metabolic & Immune Disorders Drug Targets
https://www.readbyqxmd.com/read/29141392/-the-progress-of-studies-on-aqueous-humor-dynamics-abnormality-induced-by-trabecular-meshwork-and-schlemm-canal-endothelial-cell-senescence-and-its-relation-with-glaucoma
#9
M M Song, Y Lei, J H Wu, X H Sun
Glaucoma is the second leading cause of blindness in the world next to cataract. Aging is a strong risk factor leading to elevated intraocular pressure (IOP). IOP is associated with aqueous humor circulation. Trabecular meshwork cells and Schlemm canal endothelial cells, which form the conventional outflow pathway, play an important role in maintaining the IOP. Cell senescence induces abnormalities of the aqueous humor dynamics, leading to elevated IOP. Trabecular meshwork cells cause increased intrinsic stiffness, autophagy dysfunction, abnormal expression of microRNA and mitochondrial dysfunction with senescence...
November 11, 2017: [Zhonghua Yan Ke za Zhi] Chinese Journal of Ophthalmology
https://www.readbyqxmd.com/read/29141243/trolline-ameliorates-liver-fibrosis-by-inhibiting-the-nf-%C3%AE%C2%BAb-pathway-promoting-hsc-apoptosis-and-suppressing-autophagy
#10
Facheng Bai, Quanfang Huang, Jinlan Nie, Shengjuan Lu, Chunyuan Lu, Xunshuai Zhu, Yuxin Wang, Lang Zhuo, Zhongpeng Lu, Xing Lin
BACKGROUND/AIMS: Previous studies have shown that trolline possesses various forms of pharmacological activity, including antibacterial and antiviral potency. The present paper addressed the putative hepatoprotective effects of trolline. METHODS: Rats received 2 ml/kg CCl4 (mixed 1: 1 in peanut oil) intragastrically twice a week for 8 weeks to induce hepatic fibrosis. The animals were then treated with trolline for additional 4 weeks. Liver pathology and collagen accumulation were observed by hematoxylin-eosin and Masson's trichrome staining, respectively...
November 15, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29138276/metabolic-reprogramming-ensures-cancer-cell-survival-despite-oncogenic-signaling-blockade
#11
Hui-Wen Lue, Jennifer Podolak, Kevin Kolahi, Larry Cheng, Soumya Rao, Devin Garg, Chang-Hui Xue, Juha K Rantala, Jeffrey W Tyner, Kent L Thornburg, Ann Martinez-Acevedo, Jen-Jane Liu, Christopher L Amling, Charles Truillet, Sharon M Louie, Kimberly E Anderson, Michael J Evans, Valerie B O'Donnell, Daniel K Nomura, Justin M Drake, Anna Ritz, George V Thomas
There is limited knowledge about the metabolic reprogramming induced by cancer therapies and how this contributes to therapeutic resistance. Here we show that although inhibition of PI3K-AKT-mTOR signaling markedly decreased glycolysis and restrained tumor growth, these signaling and metabolic restrictions triggered autophagy, which supplied the metabolites required for the maintenance of mitochondrial respiration and redox homeostasis. Specifically, we found that survival of cancer cells was critically dependent on phospholipase A2 (PLA2) to mobilize lysophospholipids and free fatty acids to sustain fatty acid oxidation and oxidative phosphorylation...
November 14, 2017: Genes & Development
https://www.readbyqxmd.com/read/29137937/design-synthesis-and-evaluation-of-3-arylidene-azetidin-2-ones-as-potential-antifungal-agents-against-alternaria-solani-sorauer
#12
Wang Delong, Wu Yongling, Wang Lanying, Feng Juntao, Zhang Xing
A new concise and facile method was explored to synthesize a collection of new 3-arylidene azetidin-2-ones, which could be regarded as the derivatives of the hybrid scaffold of bioactive natural cinnamamide and heterocycle azetidi-2-one. The structures of the synthesized compounds were characterized by (1)H, (13)C NMR, and MS; and their antifungal activity were evaluated against Alternaria solani Sorauer. These antifungal data were subjected to a quantitative structure-activity relationship (QSAR) analysis using Codessa software on the basis of the results from B3LYP/6-31G(d,p) quantum calculations...
November 4, 2017: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/29135861/in-vitro-and-in-vivo-antimelanoma-effect-of-ethyl-ester-cyclohexyl-analog-of-ethylenediamine-dipropanoic-acid
#13
Andjelka M Isakovic, Sasa M Petricevic, Slavica M Ristic, Dusan M Popadic, Tamara K Kravic-Stevovic, Nevena S Zogovic, Jelena M Poljarevic, Tatjana V Zivanovic Radnic, Tibor J Sabo, Aleksandra J Isakovic, Ivanka D Markovic, Vladimir S Trajkovic, Sonja T Misirlic-Dencic
Melanoma, an aggressive skin tumor with high metastatic potential, is associated with high mortality and increasing morbidity. Multiple available chemotherapeutic and immunotherapeutic modalities failed to improve survival in advanced disease, and the search for new agents is ongoing. The aim of this study was to investigate antimelanoma effects of O,O-diethyl-(S,S)-ethylenediamine-N,N'di-2-(3-cyclohexyl) propanoate dihydrochloride (EE), a previously synthesized and characterized organic compound. Mouse melanoma B16 cell viability was assessed using acid phosphatase, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, sulforhodamine B, and lactate dehydrogenase assays...
November 13, 2017: Melanoma Research
https://www.readbyqxmd.com/read/29132391/nadph-oxidases-in-parkinson-s-disease-a-systematic-review
#14
REVIEW
Karim Belarbi, Elodie Cuvelier, Alain Destée, Bernard Gressier, Marie-Christine Chartier-Harlin
Parkinson's disease (PD) is a progressive movement neurodegenerative disease associated with a loss of dopaminergic neurons in the substantia nigra of the brain. Oxidative stress, a condition that occurs due to imbalance in oxidant and antioxidant status, is thought to play an important role in dopaminergic neurotoxicity. Nicotinamide adenine dinucleotide phosphate (NADPH) oxidases are multi-subunit enzymatic complexes that generate reactive oxygen species as their primary function. Increased immunoreactivities for the NADPH oxidases catalytic subunits Nox1, Nox2 and Nox4 have been reported in the brain of PD patients...
November 13, 2017: Molecular Neurodegeneration
https://www.readbyqxmd.com/read/29130633/the-mitochondrial-metabolic-reprogramming-agent-trimetazidine-as-an-exercise-mimetic-in-cachectic-c26-bearing-mice
#15
Francesca Molinari, Fabrizio Pin, Stefania Gorini, Sergio Chiandotto, Laura Pontecorvo, Fabio Penna, Emanuele Rizzuto, Simona Pisu, Antonio Musarò, Paola Costelli, Giuseppe Rosano, Elisabetta Ferraro
BACKGROUND: Cancer cachexia is characterized by muscle depletion and exercise intolerance caused by an imbalance between protein synthesis and degradation and by impaired myogenesis. Myofibre metabolic efficiency is crucial so as to assure optimal muscle function. Some drugs are able to reprogram cell metabolism and, in some cases, to enhance metabolic efficiency. Based on these premises, we chose to investigate the ability of the metabolic modulator trimetazidine (TMZ) to counteract skeletal muscle dysfunctions and wasting occurring in cancer cachexia...
November 11, 2017: Journal of Cachexia, Sarcopenia and Muscle
https://www.readbyqxmd.com/read/29130361/mta1-is-a-novel-regulator-of-autophagy-that-induces-tamoxifen-resistance-in-breast-cancer-cells
#16
Min-Ho Lee, Dahae Koh, Hyelin Na, Na-Lee Ka, Seungsu Kim, Hyeon-Ji Kim, Sungyoul Hong, Young Kee Shin, Je Kyung Seong, Mi-Ock Lee
Tamoxifen is commonly used to treat patients with ESR/ER-positive breast cancer, but its therapeutic benefit is limited by the development of resistance. Recently, alterations in macroautophagy/autophagy function were demonstrated to be a potential mechanism for tamoxifen resistance. Although MTA1 (metastasis-associated 1) has been implicated in breast tumorigenesis and metastasis, its role in endocrine resistance has not been studied. Here, we report that the level of MTA1 expression was upregulated in the tamoxifen resistant breast cancer cell lines MCF7/TAMR and T47D/TR, and knockdown of MTA1 sensitized the cells to 4-hydroxytamoxifen (4OHT)...
November 13, 2017: Autophagy
https://www.readbyqxmd.com/read/29129519/sirt6-protects-against-hepatic-ischemia-reperfusion-injury-by-inhibiting-apoptosis-and-autophagy-related-cell-death
#17
Song Zhang, Shuai Jiang, Haiping Wang, Wencheng Di, Chao Deng, Zhenxiao Jin, Wei Yi, Xiao Xiao, Yongzhan Nie, Yang Yang
Silent information regulator 6 (SIRT6), a class III histone deacetylase, has been revealed to participate in multiple metabolic processes in the liver, and it plays important roles in protecting against ischemia/reperfusion (I/R) injury in multiple organs. In this study, we explored whether SIRT6 is protective against hepatic I/R injury and elucidated the underlying mechanisms. The expression of SIRT6 was significantly decreased during reperfusion compared with the control group. SIRT6-LKO mice exhibited significantly aggravated oxidative stress, mitochondrial dysfunction, inflammatory responses, mitogen-activated protein kinase (MAPK) signaling activation, and apoptosis and autophagy related hepatocyte death compared with control mice...
November 9, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/29129070/molecular-signatures-associated-with-treatment-of-triple-negative-mda-mb231-breast-cancer-cells-with-histone-deacetylase-inhibitors-jaha-and-saha
#18
Mariangela Librizzi, Fabio Caradonna, Ilenia Cruciata, Janusz Dębski, Supojjanee Sansook, Michał Dadlez, John Spencer, Claudio Luparello
Jay Amin hydroxamic acid (JAHA; N8-ferrocenylN(1)-hydroxy-octanediamide) is a ferrocene-containing analogue of the histone deacetylase inhibitor (HDACi) suberoylanilide hydroxamic acid (SAHA). JAHA's cytotoxic activity on MDA-MB231 triple negative breast cancer (TNBC) cells at 72 h has been previously demonstrated with an IC50 of 8.45 μM. JAHA's lethal effect was found linked to perturbations of cell cycle, mitochondrial activity, signal transduction, and autophagy mechanisms. To glean novel insights on how MDA-MB231 breast cancer cells respond to the cytotoxic effect induced by JAHA, and to compare the biological effect with the related compound SAHA, we have employed a combination of differential display-PCR, proteome analysis, and COMET assay techniques and shown some differences in the molecular signature profiles induced by exposure to either HDACis...
November 12, 2017: Chemical Research in Toxicology
https://www.readbyqxmd.com/read/29128638/ulk1-regulated-autophagy-a-mechanism-in-cellular-protection-for-aldh2-against-hyperglycemia
#19
Min Liu, Songhe Lu, Wei He, Le Zhang, Ying Ma, Ping Lv, Meijuan Ma, Wenjun Yu, Jiaxing Wang, Mingming Zhang, Yingmei Zhang, Yan Li
Mitochondrial aldehyde dehydrogenase 2 (ALDH2), an important enzyme in the elimination of toxic aldehydes, is involved in cardioprotection against diabetes mellitus. This study was designed to examine the mechanism behind ALDH2-offered protection against high glucose exposure with a focus on autophagy. H9C2 cells were cultured with normal or high glucose medium in the presence or absence of the ALDH2 agonist Alda-1. GFP-LC3 puncta and immunofluorescence were employed to assess autophagosome formation. Western blotting was applied to evaluate autophagy protein markers Atg5, LC3, p62, ULK1 phosphorylation and ALDH2...
November 8, 2017: Toxicology Letters
https://www.readbyqxmd.com/read/29127189/autophagy-promotes-escape-from-phosphatidylinositol-3-kinase-inhibition-in-estrogen-receptor-positive-breast-cancer
#20
Wei Yang, Sarah R Hosford, Nicole A Traphagen, Kevin Shee, Eugene Demidenko, Stephanie Liu, Todd W Miller
Hyperactivation of the PI3K pathway has been implicated in resistance to antiestrogen therapies in estrogen receptor α (ER)-positive breast cancer, prompting the development of therapeutic strategies to inhibit this pathway. Autophagy has tumor-promoting and -suppressing roles and has been broadly implicated in resistance to anticancer therapies, including antiestrogens. Chloroquine (CQ) is an antimalarial and amebicidal drug that inhibits autophagy in mammalian cells and human tumors. Herein, we observed that CQ inhibited proliferation and autophagy in ER(+) breast cancer cells...
November 10, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
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