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https://www.readbyqxmd.com/read/27909249/mortalin-mediated-and-erk-controlled-targeting-of-hif-1%C3%AE-to-mitochondria-confers-resistance-to-apoptosis-under-hypoxia
#1
Ilias Mylonis, Maria Kourti, Martina Samiotaki, George Panayotou, George Simos
Hypoxia inducible factor-1 (HIF-1) is the main transcriptional activator of the cellular response to hypoxia and an important target of anticancer therapy. Phosphorylation by ERK stimulates the transcriptional activity of HIF-1α by inhibiting its CRM1-dependent nuclear export. Here, we demonstrate that phosphorylation by ERK also regulates the association of HIF-1α with a novel interaction partner identified as mortalin (GRP75) which mediates non-genomic involvement of HIF-1α in apoptosis. Mortalin binds specifically to HIF-1α lacking modification by ERK and their complex is localized outside the nucleus...
December 1, 2016: Journal of Cell Science
https://www.readbyqxmd.com/read/27898307/a-ca-2-chelator-ameliorates-chromium-vi-induced-hepatocyte-l-02-injury-via-down-regulation-of-voltage-dependent-anion-channel-1-vdac1-expression
#2
Xing Yi, Fang Xiao, Xiali Zhong, Yujie Duan, Kaihua Liu, Caigao Zhong
Hexavalent chromium could result in cell malfunctions. Intracellular Ca(2+) ([Ca(2+)]i) content and VDAC1 expression are both important features related to cell survial. This study aimed to explore the mechanism of cell injury induced by Cr(VI) and tentatively offer clues to repairing this cell damage using [Ca(2+)]i and VDAC1. L-02 hepatocytes were treated with Cr(VI)/BAPTA, and the levels of [Ca(2+)]i and cell injury associated with Cr(VI) were determined in addition to the effect of BAPTA. The expression of VDAC1 in Cr(VI)-induced cells was evaluated...
November 18, 2016: Environmental Toxicology and Pharmacology
https://www.readbyqxmd.com/read/27894242/indazolo-3-2-b-quinazolinones-attack-hepatocellular-carcinoma-hep3b-cells-by-inducing-mitochondrial-dependent-apoptosis-and-inhibition-of-nrf2-are-signaling-pathway
#3
Y Zhang, R Qiao, D He, Z Zhao, S Yang, H Zou, X Zhang, M Wu, J Chen, P Chen
Hepatocellular carcinoma (HCC) is the second leading cause of cancer death worldwide. Genotoxic stress resistance in patients often contributes to poor clinical outcomes, and is intensively associated to the upregulation of Nrf2/ARE signaling pathway. In this study, we examined the connection between the anti-cancer activity of two novel indazolo[3,2-b]quinazolinone (IQ) derivatives, IQ-7 and IQ-12, and their effect on the Nrf2/ARE signaling pathway. The two compounds were shown to induce apoptosis and inhibit the Nrf2/ARE signaling pathway in Hep3B cells (human hepatoma cell line)...
November 28, 2016: Current Molecular Medicine
https://www.readbyqxmd.com/read/27891320/the-association-of-vdac-with-cell-viability-of-pc12-model-of-huntington-s-disease
#4
Andonis Karachitos, Daria Grobys, Klaudia Kulczyńska, Adrian Sobusiak, Hanna Kmita
It is becoming increasingly apparent that mitochondria dysfunction plays an important role in the pathogenesis of Huntington's disease (HD), but the underlying mechanism is still elusive. Thus, there is a still need for further studies concerning the upstream events in the mitochondria dysfunction that could contribute to cell death observed in HD. Taking into account the fundamental role of the voltage-dependent anion-selective channel (VDAC) in mitochondria functioning, it is reasonable to consider the channel as a crucial element in HD etiology...
2016: Frontiers in Oncology
https://www.readbyqxmd.com/read/27859782/inhibition-of-the-mitochondrial-calcium-uniporter-mcu-rescues-dopaminergic-neurons-in-pink1-zebrafish
#5
Smijin Soman, Marcus Keatinge, Mahsa Moein, Marc DaCosta, Heather Mortiboys, Alexander Skupin, Sreedevi Sugunan, Michal Bazala, Jacek Kuznicki, Oliver Bandmann
Mutations in PTEN-induced putative kinase 1 (PINK1) are a cause of early onset Parkinson's disease (PD). Loss of PINK1 function causes dysregulation of mitochondrial calcium homeostasis, resulting in mitochondrial dysfunction and neuronal cell death. We report that both genetic and pharmacological inactivation of the mitochondrial calcium uniporter (MCU), located in the inner mitochondrial membrane, prevents dopaminergic neuronal cell loss in pink1(Y431) * mutant zebrafish (Danio rerio) via rescue of mitochondrial respiratory chain function...
November 12, 2016: European Journal of Neuroscience
https://www.readbyqxmd.com/read/27816759/brain-quantitative-proteomic-responses-reveal-new-insight-of-benzotriazole-neurotoxicity-in-female-chinese-rare-minnow-gobiocypris-rarus
#6
Xuefang Liang, Christopher J Martyniuk, Jinmiao Zha, Zijian Wang
Benzotriazole (BT) is a high-production volume chemical which has been ubiquitously detected in aquatic environments. Although adverse effects from acute and chronic exposure to BT have been reported, the neurotoxic effect of BT and the mechanisms of toxicity are not well documented. In this study, adult female Chinese rare minnow (Gobiocypris rarus) were exposed to 0.05, 0.5, and 5mg/L BT for 28days. The brain proteome showed that BT exposure mainly involved in metabolic process, signal transduction, stress response, cytoskeleton, and transport...
December 2016: Aquatic Toxicology
https://www.readbyqxmd.com/read/27814578/lipid-raft-er-signalosome-malfunctions-in-menopause-and-alzheimer-s-disease
#7
Ana Canerina-Amaro, Luis G Hernandez-Abad, Isidre Ferrer, David Quinto-Alemany, Fatima Mesa-Herrera, Carla Ferri, Ricardo A Puertas-Avendano, Mario Diaz, Raquel Marin
The increase in the incidence of Alzheimer's disease (AD) in old women may be attributable to estrogen deficiency, and estrogen replacement therapy may be useful in preventing or delaying the onset of this disease. In neuronal membranes, 17 beta-estradiol interacts with estrogen receptors (mERs) located in lipid raft signalosomes which trigger neuroprotective responses by anchoring to scaffolding caveolin-1 complexed with other proteins. We suggest that mER-signalosome malfunctions in AD and by menopause due to development of aberrations in these microstructures...
January 1, 2017: Frontiers in Bioscience (Scholar Edition)
https://www.readbyqxmd.com/read/27796346/lncrna-h19-mir-675-axis-regulates-cardiomyocyte-apoptosis-by-targeting-vdac1-in-diabetic-cardiomyopathy
#8
Xiangquan Li, Hao Wang, Biao Yao, Weiting Xu, Jianchang Chen, Xiang Zhou
We previously established a rat model of diabetic cardiomyopathy (DCM) and found that the expression of lncRNA H19 was significantly downregulated. The present study was designed to investigate the pathogenic role of H19 in the development of DCM. Overexpression of H19 in diabetic rats attenuated oxidative stress, inflammation and apoptosis, and consequently improved left ventricular function. High glucose was associated with reduced H19 expression and increased cardiomyocyte apoptosis. To explore the molecular mechanisms involved, we performed in vitro experiments using cultured neonatal rat cardiomyocytes...
October 31, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27778231/identification-of-potential-predictive-markers-of-dexamethasone-resistance-in-childhood-acute-lymphoblastic-leukemia
#9
Nasrin Dehghan-Nayeri, Mostafa Rezaei-Tavirani, Mir Davood Omrani, Ahmad Gharehbaghian, Kourosh Goudarzi Pour, Peyman Eshghi
Response to dexamethasone (DEXA), as a hallmark drug in the treatment of childhood acute lymphoblastic leukemia (ALL), is one of the pivotal prognostic factors in the prediction of outcome in ALL. Identification of predictive markers of chemoresistance is beneficial to selecting of the best therapeutic protocol with the lowest effect adverse. Hence, we aimed to find drug targets using the 2DE/MS proteomics study of a DEXA-resistant cell line (REH) as a model for poor DEXA responding patients before and after drug treatment...
October 24, 2016: Journal of Cell Communication and Signaling
https://www.readbyqxmd.com/read/27761954/novel-insights-into-role-of-mir-320a-vdac1-axis-in-astrocyte-mediated-neuronal-damage-in-neuroaids
#10
Mahar Fatima, Bharat Prajapati, Kanza Saleem, Rina Kumari, Chitra Mohindar Singh Singal, Pankaj Seth
Astroglia are indispensable component of the tripartite synapse ensheathing innumerous soma and synapses. Its proximity to neurons aids the regulation of neuronal functions, health and survival through dynamic neuroglia crosstalk. Susceptibility of astrocyte to HIV-1 infection and subsequent latency culminates in compromised neuronal health. The viral protein HIV-1 transactivator of transcription (Tat) is neurotoxic. HIV-1 Tat is detected in brain of AIDS patients even in cases where viral load is non-detectable due to successful HAART therapy...
October 20, 2016: Glia
https://www.readbyqxmd.com/read/27738100/novel-compounds-targeting-the-mitochondrial-protein-vdac1-inhibit-apoptosis-and-protect-against-mitochondrial-dysfunction
#11
Danya Ben-Hail, Racheli Begas-Shvartz, Moran Shalev, Anna Shteinfer-Kuzmine, Arie Gruzman, Simona Reina, Vito De Pinto, Varda Shoshan-Barmatz
Apoptosis is thought to play a critical role in several pathological processes, such as neurodegenerative diseases (i.e. Parkinson's and Alzheimer's diseases) and various cardiovascular diseases. Despite the fact that apoptotic mechanisms are well defined, there is still no substantial therapeutic strategy to stop or even slow this process. Thus, there is an unmet need for therapeutic agents that are able to block or slow apoptosis in neurodegenerative and cardiovascular diseases. The outer mitochondrial membrane protein voltage-dependent anion channel 1 (VDAC1) is a convergence point for a variety of cell survival and death signals, including apoptosis...
November 25, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27721436/hexokinase-i-n-terminal-based-peptide-prevents-the-vdac1-sod1-g93a-interaction-and-re-establishes-als-cell-viability
#12
Andrea Magrì, Ramona Belfiore, Simona Reina, Marianna Flora Tomasello, Maria Carmela Di Rosa, Francesca Guarino, Loredana Leggio, Vito De Pinto, Angela Messina
Superoxide Dismutase 1 mutants associate with 20-25% of familial Amyotrophic Lateral Sclerosis (ALS) cases, producing toxic aggregates on mitochondria, notably in spinal cord. The Voltage Dependent Anion Channel isoform 1 (VDAC1) in the outer mitochondrial membrane is a docking site for SOD1 G93A mutant in ALS mice and the physiological receptor of Hexokinase I (HK1), which is poorly expressed in mouse spinal cord. Our results demonstrate that HK1 competes with SOD1 G93A for binding VDAC1, suggesting that in ALS spinal cord the available HK1-binding sites could be used by SOD1 mutants for docking mitochondria, producing thus organelle dysfunction...
October 10, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27677502/protein-coingestion-with-alcohol-following-strenuous-exercise-attenuates-alcohol-induced-intramyocellular-apoptosis-and-inhibition-of-autophagy
#13
William J Smiles, Evelyn B Parr, Vernon G Coffey, Orly Lacham-Kaplan, John A Hawley, Donny M Camera
Alcohol ingestion decreases post-exercise rates of muscle protein synthesis, but the mechanism(s) (e.g., increased protein breakdown) underlying this observation are unknown. Autophagy is an intracellular "recycling" system required for homeostatic substrate and organelle turnover; its dysregulation may provoke apoptosis and lead to muscle atrophy. We investigated the acute effects of alcohol ingestion on autophagic cell signaling responses to a bout of concurrent (combined resistance- and endurance-based) exercise...
September 27, 2016: American Journal of Physiology. Endocrinology and Metabolism
https://www.readbyqxmd.com/read/27659305/a-single-talent-immunogenic-membrane-antigen-and-novel-prognostic-predictor-voltage-dependent-anion-channel-1-vdac1-in-pancreatic-cancer
#14
Weibin Wang, Taiping Zhang, Wenjing Zhao, Lai Xu, Yu Yang, Quan Liao, Yupei Zhao
Immunogenic membrane antigens associated with multiple biological functions of human cancer cells, have significant value in molecule diagnosis and targeted therapy. Here we screened immunogenic membrane antigens in pancreatic cancer by immunobloting IgG purified from sera of 66 pancreatic cancer patients with membrane proteins separated from two-dimensional PAGE of human pancreatic cancer cell line SWl990, and identified voltage-dependent anion channel 1 (VDAC1) as one of the potential immunogenic membrane antigens...
2016: Scientific Reports
https://www.readbyqxmd.com/read/27643450/mitochondrial-porin-isoform-atvdac1-regulates-the-competence-of-arabidopsis-thaliana-to-agrobacterium-mediated-genetic-transformation
#15
Tackmin Kwon
The efficiency of Agrobacterium-mediated transformation in plants depends on the virulence of Agrobacterium strains, the plant tissue culture conditions, and the susceptibility of host plants. Understanding the molecular interactions between Agrobacterium and host plant cells is crucial when manipulating the susceptibility of recalcitrant crop plants and protecting orchard trees from crown gall disease. It was discovered that Arabidopsis voltage-dependent anion channel 1 (atvdac1) mutant has drastic effects on Agrobacterium-mediated tumorigenesis and growth developmental phenotypes, and that these effects are dependent on a Ws-0 genetic background...
September 2016: Molecules and Cells
https://www.readbyqxmd.com/read/27625993/news-about-vdac1-in-hypoxia
#16
N M Mazure
The voltage-dependent anion channel (VDAC) is the main interface between the cytosol and mitochondria of cells. It plays a crucial role in both mitochondrial metabolism and cell death. The main basic function of this channel is to mediate and gate the flux of small ions, metabolites, and adenosine triphosphate. Changes in its structure, and thus conformation, are expected to affect its activity and modulate the ability of cancer cells to expand. In this review, we describe a novel mechanism by which mitochondria of cells in hypoxia, a low level of oxygen, protects from apoptosis...
2016: Frontiers in Oncology
https://www.readbyqxmd.com/read/27589771/hierridin-b-isolated-from-a-marine-cyanobacterium-alters-vdac1-mitochondrial-activity-and-cell-cycle-genes-on-ht-29-colon-adenocarcinoma-cells
#17
Sara Freitas, Rosário Martins, Margarida Costa, Pedro N Leão, Rui Vitorino, Vitor Vasconcelos, Ralph Urbatzka
BACKGROUND: Hierridin B was isolated from a marine cyanobacterium Cyanobium sp. strain and induced cytotoxicity selectively in HT-29 adenocarcinoma cells. The underlying molecular mechanism was not yet elucidated. METHODS: HT-29 cells were exposed to the IC50 concentration of hierridin B (100.2 μM) for 48 h. Non-targeted proteomics was performed using 2D gel electrophoresis and MALDI-TOF/TOF mass spectrometry. The mRNA expression of apoptotic and cell cycle genes were analyzed by real-time PCR...
August 31, 2016: Marine Drugs
https://www.readbyqxmd.com/read/27553862/mir-29a-differentially-regulates-cell-survival-in-astrocytes-from-cornu-ammonis-1-and-dentate-gyrus-by-targeting-vdac1
#18
Creed M Stary, Xiaoyun Sun, YiBing Ouyang, Le Li, Rona G Giffard
Neurons in the cornu ammonis 1 (CA1) region of the hippocampus are vulnerable to cerebral ischemia, while dentate gyrus (DG) neurons are more resistant. This effect is mediated by local astrocytes, and may reflect differences in subregional hippocampal expression of miR-29a. We investigated the role of miR-29a on survival of hippocampal astrocytes cultured selectively from CA1 and DG in response to glucose deprivation (GD). CA1 astrocytes exhibited more cell death and a greater decrease in miR-29a than DG astrocytes...
September 2016: Mitochondrion
https://www.readbyqxmd.com/read/27544294/in-silico-construction-of-hk2-vdac1-complex-and-investigating-the-hk2-binding-induced-molecular-gating-mechanism-of-vdac1
#19
Dawei Zhang, Yew Mun Yip, Liben Li
Hexokinase 2 (HK2) binds to Voltage-Dependent Anion Channel 1 (VDAC1) on mitochondrial outer membrane (MOM) to facilitate a preferential access of ATP to HK2 for glycolysis, in order to maintain a constant energy source for cell proliferation in cancer especially. While previous studies have discovered that the VDAC1 N-terminal helix is responsible for regulating molecules from within mitochondria to cytoplasm, the molecular mechanism of how HK2 is able to regulate the ATP access remains elusive. We hereby propose a model for the HK2-VDAC1 association...
September 2016: Mitochondrion
https://www.readbyqxmd.com/read/27543827/changes-of-tspo-mediated-mitophagy-signaling-pathway-in-learned-helplessness-mice
#20
Dongmei Li, Ji Zheng, Mingyang Wang, Lu Feng, Zhili Ren, Yanyong Liu, Nan Yang, Pingping Zuo
Low response rate was witnessed with the present monoaminergic based antidepressants, urging a need for new therapeutic target identification. Accumulated evidences strongly suggest that mitochondrial deficit is implicated in major depression and 18kDa translocator protein (TSPO) plays an important role in regulating mitochondrial function. However the changes of TSPO and TSPO mediated mitophagy pathway in the depressive brain is unclear. In present study, a well validated animal model of depression, learned helplessness (LH), was employed to investigate the relevant changes...
November 30, 2016: Psychiatry Research
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