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https://www.readbyqxmd.com/read/28928465/endothelial-adenosine-a2a-receptor-mediated-glycolysis-is-essential-for-pathological-retinal-angiogenesis
#1
Zhiping Liu, Siyuan Yan, Jiaojiao Wang, Yiming Xu, Yong Wang, Shuya Zhang, Xizhen Xu, Qiuhua Yang, Xianqiu Zeng, Yaqi Zhou, Xuejiao Gu, Sarah Lu, Zhongjie Fu, David J Fulton, Neal L Weintraub, Ruth B Caldwell, Wenbo Zhang, Chaodong Wu, Xiao-Ling Liu, Jiang-Fan Chen, Aftab Ahmad, Ismail Kaddour-Djebbar, Mohamed Al-Shabrawey, Qinkai Li, Xuejun Jiang, Ye Sun, Akrit Sodhi, Lois Smith, Mei Hong, Yuqing Huo
Adenosine/adenosine receptor-mediated signaling has been implicated in the development of various ischemic diseases, including ischemic retinopathies. Here, we show that the adenosine A2a receptor (ADORA2A) promotes hypoxia-inducible transcription factor-1 (HIF-1)-dependent endothelial cell glycolysis, which is crucial for pathological angiogenesis in proliferative retinopathies. Adora2a expression is markedly increased in the retina of mice with oxygen-induced retinopathy (OIR). Endothelial cell-specific, but not macrophage-specific Adora2a deletion decreases key glycolytic enzymes and reduces pathological neovascularization in the OIR mice...
September 19, 2017: Nature Communications
https://www.readbyqxmd.com/read/28924365/effects-of-hypobaric-hypoxia-on-rat-retina-and-protective-response-of-resveratrol-to-the-stress
#2
Xiaorong Xin, Hong Dang, Xiaojing Zhao, Haohao Wang
High-altitude retinopathy represents retinal functional changes associated with environmental challenges imposed by hypobaric hypoxia, but the detailed cellular and molecular mechanism underlying this process remains unclear. Our current investigation was to explore the effect of hypobaric hypoxia on the rat retina and determine whether resveratrol has a protective efficacy on the hypoxic damage to the retina. Experiment rats were randomly grouped as the control group, hypoxia group and resveratrol intervention group...
2017: International Journal of Medical Sciences
https://www.readbyqxmd.com/read/28912885/brusatol-mediated-inhibition-of-c-myc-increases-hif-1%C3%AE-degradation-and-causes-cell-death-in-colorectal-cancer-under-hypoxia
#3
Eun-Taex Oh, Chan Woo Kim, Ha Gyeong Kim, Jae-Seon Lee, Heon Joo Park
HIF-1 (hypoxia-inducible factor-1) regulates the expression of ~100 genes involved in angiogenesis, metastasis, tumor growth, chemoresistance and radioresistance, underscoring the growing interest in targeting HIF-1 for cancer control. In the present study, we investigated the molecular mechanisms underlying brusatol-induced HIF-1α degradation and cell death in colorectal cancer under hypoxia (0.5% O2). Under hypoxia, pretreatment of cancer cells with brusatol increased HIF-1α degradation and cancer cell death in a dose-dependent manner...
2017: Theranostics
https://www.readbyqxmd.com/read/28894274/kdm4a-regulates-hif-1-levels-through-h3k9me3
#4
Grzegorz Dobrynin, Tom E McAllister, Katarzyna B Leszczynska, Shaliny Ramachandran, Adam J Krieg, Akane Kawamura, Ester M Hammond
Regions of hypoxia (low oxygen) occur in most solid tumours and cells in these areas are the most aggressive and therapy resistant. In response to decreased oxygen, extensive changes in gene expression mediated by Hypoxia-Inducible Factors (HIFs) contribute significantly to the aggressive hypoxic tumour phenotype. In addition to HIFs, multiple histone demethylases are altered in their expression and activity, providing a secondary mechanism to extend the hypoxic signalling response. In this study, we demonstrate that the levels of HIF-1α are directly controlled by the repressive chromatin mark, H3K9me3...
September 11, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28894087/hypoxia-inducible-factor-hif-1-promotes-myeloid-derived-suppressor-cells-accumulation-through-entpd2-cd39l1-in-hepatocellular-carcinoma
#5
David Kung-Chun Chiu, Aki Pui-Wah Tse, Iris Ming-Jing Xu, Jane Di Cui, Robin Kit-Ho Lai, Lynna Lan Li, Hui-Yu Koh, Felice Ho-Ching Tsang, Larry Lai Wei, Chun-Ming Wong, Irene Oi-Lin Ng, Carmen Chak-Lui Wong
Myeloid-derived suppressor cells (MDSCs) possess immunosuppressive activities, which allow cancers to escape immune surveillance and become non-responsive to immune checkpoints blockade. Here we report hypoxia as a cause of MDSC accumulation. Using hepatocellular carcinoma (HCC) as a cancer model, we show that hypoxia, through stabilization of hypoxia-inducible factor-1 (HIF-1), induces ectoenzyme, ectonucleoside triphosphate diphosphohydrolase 2 (ENTPD2/CD39L1), in cancer cells, causing its overexpression in HCC clinical specimens...
September 11, 2017: Nature Communications
https://www.readbyqxmd.com/read/28889102/caenorhabditis-elegans-hif-1-is-broadly-required-for-survival-in-hydrogen-sulfide
#6
Irini Topalidou, Dana L Miller
Hydrogen sulfide is common in the environment, and is also endogenously produced by animal cells. Although hydrogen sulfide is often toxic, exposure to low levels of hydrogen sulfide improves outcome in a variety of mammalian models of ischemia-reperfusion injury. In Caenorhabditis elegans, the initial transcriptional response to hydrogen sulfide depends on the hif-1 transcription factor, and hif-1 mutant animals die when exposed to hydrogen sulfide. In this study, we use rescue experiments to identify tissues in which hif-1 is required to survive exposure to hydrogen sulfide...
September 9, 2017: G3: Genes—Genomes—Genetics
https://www.readbyqxmd.com/read/28873177/hypoxia-inducible-factor-dependent-expression-of-angiopoietin-like-4-by-conjunctival-epithelial-cells-promotes-the-angiogenic-phenotype-of-pterygia
#7
Qianli Meng, Yaowu Qin, Monika Deshpande, Fabiana Kashiwabuchi, Murilo Rodrigues, Qiaozhi Lu, Hui Ren, Jennifer H Elisseeff, Gregg L Semenza, Silvia V Montaner, Akrit Sodhi
Purpose: Disappointing results from clinical studies assessing the efficacy of therapies targeting vascular endothelial growth factor (VEGF) for the treatment of pterygia suggest that other angiogenic mediators may also play a role in its development. We therefore explore the relative contribution of VEGF, hypoxia-inducible factor (HIF)-1α (the transcription factor that regulates VEGF expression in ocular neovascular disease), and a second HIF-regulated mediator, angiopoietin-like 4 (ANGPTL4), to the angiogenic phenotype of pterygia...
September 1, 2017: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/28866816/distinctively-expressed-cytokines-by-three-different-inflammation-cells-and-their-interaction-with-keratinocytes-in-wound-healing
#8
Jingwen Wang, Xusheng Wang, Haiyan Chen, Jianjun Liu, Edward E Tredget, Yaojiong Wu
Inflammatory cells exert crucial influence on wound healing, while exploration is still desired to get further insight into the key factors that promote the process. In the present study, we performed comparative microarray data analysis of the three types of inflammatory cells isolated from skin wounds and focused on differentially expressed secreted factors. Gene Ontology enrichment and receptor analysis indicated that 11 genes of secreted factors in Ly6C(+) inflammatory macrophages and 27 genes of secreted factors in neutrophils exhibited higher (≥ 5-fold) expression, and all these factors were considered as candidates with potentially important role in keratinocyte activation...
September 2, 2017: Inflammation
https://www.readbyqxmd.com/read/28860539/hypoxia-induces-cancer-associated-camp-pka-signalling-through-hif-mediated-transcriptional-control-of-adenylyl-cyclases-vi-and-vii
#9
Veronika Simko, Filippo Iuliano, Andrea Sevcikova, Martina Labudova, Monika Barathova, Peter Radvak, Silvia Pastorekova, Jaromir Pastorek, Lucia Csaderova
Hypoxia is a phenomenon often arising in solid tumours, linked to aggressive malignancy, bad prognosis and resistance to therapy. Hypoxia-inducible factor-1 has been identified as a key mediator of cell and tissue adaptation to hypoxic conditions through transcriptional activation of many genes involved in glucose metabolism and other cancer-related processes, such as angiogenesis, cell survival and cell invasion. Cyclic adenosine 3'5'-monophosphate is one of the most ancient and evolutionarily conserved signalling molecules and the cAMP/PKA signalling pathway plays an important role in cellular adaptation to hypoxia...
August 31, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28857653/polo-like-kinase-3-hypoxic-responses-and-tumorigenesis
#10
Dazhong Xu, Wei Dai, Cen Li
The cellular hypoxic response contributes to cell transformation and tumor progression. Hypoxia-inducible factor 1 (HIF-1) is a key transcription factor that mediates transcription of genes whose products are essential for cellular adaptation to hypoxia. The activity of HIF-1 is largely regulated by the abundance of its alpha subunit (HIF-1α), which is primarily regulated by an oxygen-dependent and ubiquitin/proteasome-mediated degradation process. The HIF-1α protein level is also regulated by protein kinases through phosphorylation...
August 31, 2017: Cell Cycle
https://www.readbyqxmd.com/read/28855849/arnt-is-a-potential-direct-hif-1-target-gene-in-human-hep3b-hepatocellular-carcinoma-cells
#11
Markus Mandl, Reinhard Depping
BACKGROUND: The transcription factor aryl hydrocarbon receptor nuclear translocator (ARNT) participates in the hypoxia-inducible factor (HIF) pathway which senses a decline in cellular oxygen tension. In hypoxia, HIF-1α and ARNT form the transcriptional active complex HIF-1 followed by the expression of target genes. ARNT is considered as constitutively expressed and unaffected by hypoxia. However, certain tumour cell lines derived from different entities are capable to elevate ARNT expression under hypoxic conditions which implies a survival benefit...
2017: Cancer Cell International
https://www.readbyqxmd.com/read/28855210/cd73-promotes-resistance-to-her2-erbb2-antibody-therapy
#12
Martin Turcotte, David Allard, Deepak Mittal, Yacine Bareche, Laurence Buisseret, Vinu Jose, Sandra Pommey, Vincent Delisle, Sherene Loi, Heikki Joensuu, Pirkko-Liisa Kellokumpu-Lehtinen, Christos Sotiriou, Mark J Smyth, John Stagg
Expression of the ectonucleotidase CD73 by tumor cells, stromal cells, and immune cells is associated in cancer with immune suppression. In this study, we investigated the role of CD73 on the activity of the anti-HER2/ErbB2 monoclonal antibody (mAb) trastuzumab. In a prospective randomized phase III clinical trial evaluating the activity of trastuzumab, high levels of CD73 gene expression associated significantly with poor clinical outcome. In contrast, high levels of PD-1 and PD-L1 associated with improved clinical outcome...
August 30, 2017: Cancer Research
https://www.readbyqxmd.com/read/28835201/irak-m-alters-the-polarity-of-macrophages-to-facilitate-the-survival-of-mycobacterium-tuberculosis
#13
Pei Shen, Quan Li, Jilei Ma, Maopeng Tian, Fei Hong, Xinjie Zhai, Jianrong Li, Hanju Huang, Chunwei Shi
BACKGROUND: Intracellular bacterium, Mycobacterium tuberculosis (M. tb), infects specifically macrophages as host cells. IRAK-M, a member of IRAK family, is a negative regulator in TLR signaling and specifically expresses in monocytes and macrophages. The role of IRAK-M in intracellular growth of M. tb and macrophage polarization was explored, for deeply understanding the pathogenesis of M. tb, the significance of IRAK-M to innate immunity and pathogen-host interaction. METHODS: IRAK-M expression was detected in M...
August 23, 2017: BMC Microbiology
https://www.readbyqxmd.com/read/28828258/the-key-role-of-microtubules-in-hypoxia-preconditioning-induced-nuclear-translocation-of-hif-1%C3%AE-in-rat-cardiomyocytes
#14
Hai Guo, Hong Zheng, Jianjiang Wu, Hai-Ping Ma, Jin Yu, Maimaitili Yiliyaer
BACKGROUND: Hypoxia-inducible factor (HIF)-1 is involved in the regulation of hypoxic preconditioning in cardiomyocytes. Under hypoxic conditions, HIF-1α accumulates and is translocated to the nucleus, where it forms an active complex with HIF-1β and activates transcription of approximately 60 kinds of hypoxia-adaptive genes. Microtubules are hollow tubular structures in the cell that maintain cellular morphology and that transport substances. This study attempted to clarify the role of microtubule structure in the endonuclear aggregation of HIF-1α following hypoxic preconditioning of cardiomyocytes...
2017: PeerJ
https://www.readbyqxmd.com/read/28821596/hypoxia-decreases-creatine-uptake-in-cardiomyocytes-while-creatine-supplementation-enhances-hif-activation
#15
Lucia Santacruz, Antonio Jose Luis Arciniegas, Marcus Darrabie, Jose G Mantilla, Rebecca M Baron, Dawn E Bowles, Rajashree Mishra, Danny O Jacobs
Creatine (Cr), phosphocreatine (PCr), and creatine kinases (CK) comprise an energy shuttle linking ATP production in mitochondria with cellular consumption sites. Myocytes cannot synthesize Cr: these cells depend on uptake across the cell membrane by a specialized creatine transporter (CrT) to maintain intracellular Cr levels. Hypoxia interferes with energy metabolism, including the activity of the creatine energy shuttle, and therefore affects intracellular ATP and PCr levels. Here, we report that exposing cultured cardiomyocytes to low oxygen levels rapidly diminishes Cr transport by decreasing Vmax and Km Pharmacological activation of AMP-activated kinase (AMPK) abrogated the reduction in Cr transport caused by hypoxia...
August 2017: Physiological Reports
https://www.readbyqxmd.com/read/28819918/network-analysis-of-se-and-zn-related-proteins-in-the-serum-proteomics-expression-profile-of-the-endemic-dilated-cardiomyopathy-keshan-disease
#16
Sen Wang, Yanyan Lv, Yingting Wang, Peiru Du, Wuhong Tan, Mikko J Lammi, Xiong Guo
Keshan disease (KD) is an endemic cardiomyopathy with high mortality. Selenium (Se) and zinc (Zn) deficiencies are closely related to KD. The molecular mechanism of KD pathogenesis is still unclear. There are only few studies on the interaction of trace elements and proteins associated with the pathogenesis of KD. In this study, isobaric tags for relative and absolute quantitation (iTRAQ)-coupled two-dimensional liquid chromatography tandem mass spectrometry (2DLC-MS/MS) technique analysis was used to analyze the differential expression of proteins from serum samples...
August 18, 2017: Biological Trace Element Research
https://www.readbyqxmd.com/read/28819544/hypoxia-downregulates-mapk-erk-but-not-stat3-signaling-in-ros-dependent-and-hif-1-independent-manners-in-mouse-embryonic-stem-cells
#17
Jan Kučera, Julie Netušilová, Stanislava Sladeček, Martina Lánová, Ondřej Vašíček, Kateřina Štefková, Jarmila Navrátilová, Lukáš Kubala, Jiří Pacherník
Hypoxia is involved in the regulation of stem cell fate, and hypoxia-inducible factor 1 (HIF-1) is the master regulator of hypoxic response. Here, we focus on the effect of hypoxia on intracellular signaling pathways responsible for mouse embryonic stem (ES) cell maintenance. We employed wild-type and HIF-1α-deficient ES cells to investigate hypoxic response in the ERK, Akt, and STAT3 pathways. Cultivation in 1% O2 for 24 h resulted in the strong dephosphorylation of ERK and its upstream kinases and to a lesser extent of Akt in an HIF-1-independent manner, while STAT3 phosphorylation remained unaffected...
2017: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/28814529/selective-hif-1-regulation-under-nonhypoxic-conditions-by-the-p42-p44-map-kinase-inhibitor-pd184161
#18
Maroua Jalouli, Sophie Mokas, Catherine A Turgeon, Laurent Lamalice, Darren E Richard
Hypoxia-inducible factor-1 (HIF-1) is a key gene regulator for cellular adaptation to low oxygen. In addition to hypoxia, several nonhypoxic stimuli, including hormones and growth factors, are an essential part for cell-specific HIF-1 regulation. Our studies have highlighted angiotensin II (AngII), a vasoactive hormone, as a potent HIF-1 activator in vascular smooth muscle cells (VSMC). AngII increases HIF-1 transcriptional activity by modulating specific signaling pathways. In VSMC, p42/p44 mitogen-activated protein kinase (MAPK) pathway activation is essential for HIF-1-mediated transcription during AngII treatment...
August 16, 2017: Molecular Pharmacology
https://www.readbyqxmd.com/read/28801636/inhibition-of-hypoxic-response-decreases-stemness-and-reduces-tumorigenic-signaling-due-to-impaired-assembly-of-hif1-transcription-complex-in-pancreatic-cancer
#19
Olivia McGinn, Vineet K Gupta, Patricia Dauer, Nivedita Arora, Nikita Sharma, Alice Nomura, Vikas Dudeja, Ashok Saluja, Sulagna Banerjee
Pancreatic tumors are renowned for their extremely hypoxic centers, resulting in upregulation of a number of hypoxia mediated signaling pathways including cell proliferation, metabolism and cell survival. Previous studies from our laboratory have shown that Minnelide, a water-soluble pro-drug of triptolide (anti-cancer compound), decreases viability of cancer cells in vitro as well as in vivo. However, its mechanism of action remain elusive. In the current study we evaluated the effect of Minnelide, on hypoxia mediated oncogenic signaling as well as stemness in pancreatic cancer...
August 11, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28789687/long-non-coding-rna-and-tumor-hypoxia-new-players-ushered-toward-an-old-arena
#20
REVIEW
Jing-Wen Shih, Hsing-Jien Kung
Hypoxia is a classic feature of the tumor microenvironment with a profound impact on cancer progression and therapeutic response. Activation of complex hypoxia pathways orchestrated by the transcription factor HIF (hypoxia-inducible factor) contributes to aggressive phenotypes and metastasis in numerous cancers. Over the past few decades, exponentially growing research indicated the importance of the non-coding genome in hypoxic tumor regions. Recently, key roles of long non coding RNAs (lncRNAs) in hypoxia-driven cancer progression have begun to emerge...
August 8, 2017: Journal of Biomedical Science
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