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hypoxic transcription factor

Yiyi Yu, Ke Peng, Hong Li, Rongyuan Zhuang, Yan Wang, Wei Li, Shan Yu, Li Liang, Xiaojing Xu, Tianshu Liu
FoxO transcription factors are important regulators of cell survival in response to a variety of stress stimuli and play vital functions in tumor progression. However, the functions and underlying regulators of FoxO3a in colorectal cancer (CRC) have not been fully elucidated. The aim of the current study was to identify the functions of FoxO3a in CRC and characterize the transcription elements within the promoter region of FoxO3a. The expression of FoxO3a was upregulated in response to hypoxic and oxidative stress stimuli...
May 2018: Oncology Reports
Marianne S Joerger-Messerli, Byron Oppliger, Marialuigia Spinelli, Gierin Thomi, Ivana di Salvo, Philipp Schneider, Andreina Schoeberlein
Hypoxic-ischemic (HI) insult in the perinatal phase harbors a high risk of encephalopathy in the neonate. Brain cells undergo apoptosis, initiating neurodegeneration. So far, therapeutic approaches such as cooling remain limited. Transplantation of mesenchymal stem cells (MSCs) exhibits therapeutic success despite the short-time survival in the host brain, providing strong evidence that their beneficial effects are largely based on secreted factors, including extracellular vesicles (EVs). The aim of this study was to investigate the effects of human Wharton's jelly MSC (hWJ-MSC)-derived EVs on neuroprotection and neuroregeneration, using an in vitro model of oxygen-glucose deprivation/reoxygenation (OGD/R) mimicking HI injury in the mouse neuroblastoma cell line neuro2a (N2a)...
January 2018: Cell Transplantation
Hadas Pahima, Simona Reina, Noa Tadmor, Daniella Dadon-Klein, Anna Shteinfer-Kuzmine, Nathalie M Mazure, Vito De Pinto, Varda Shoshan-Barmatz
The voltage-dependent anion channel 1 (VDAC1), an outer mitochondria membrane (OMM) protein, serves as a mitochondrial gatekeeper, mediating the transport of nucleotides, Ca2+ and other metabolites across the OMM. VDAC1 also plays a central role in mitochondria-mediated apoptosis by facilitating the release of apoptotic proteins and by association with both pro- and anti-apoptotic proteins. Tumor cells, which are constantly exposed to hypoxic conditions, affect the cell via the transcription factor hypoxia-inducible factor (HIF) that induces transcriptional activity...
February 27, 2018: Oncotarget
Regina Trollmann, Theresa Mühlberger, Mandy Richter, Gudrun Boie, Andreas Feigenspan, Florian Brackmann, Susan Jung
Angiogenesis due to hypoxic-ischemic (HI) injury represents a crucial compensatory mechanism of the developing brain that is mainly regulated by hypoxia-inducible transcription factors (HIF). Pharmacological stimulation of HIF is suggested as a neuroprotective option, however, studies of its effects on vascular development are limited. We analyzed the influence of the prolyl-4-hydroxylase inhibitor (PHI), FG-4497, and erythropoietin (rhEPO) on post-hypoxic angiogenesis (angiogenic growth factors, vessel structures) in the developing mouse brain (P7) assessed after a regeneration period of 72 h...
March 13, 2018: Brain Research
Yun Bai, Chuan Liu, Lei Fu, Xiaoshan Gong, Ce Dou, Zhen Cao, Hongyu Quan, Jianmei Li, Fei Kang, Jingjin Dai, Chunrong Zhao, Shiwu Dong
Endochondral ossification is crucial for bone formation in both adult bone repair process and embryo long-bone development. In endochondral ossification, bone marrow-derived mesenchymal stem cells (BMSCs) first differentiate to chondrocyte, BMSC-derived chondrocyte then endure a hypertrophic process to generate new bone. Endochondral ossification-based bone repair is a promising strategy to cure massive bone defect, which is a major clinical issue in orthopedics. However, challenges still remain for this novel strategy...
March 16, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
Kinga A Kocemba-Pilarczyk, Barbara Ostrowska, Sonia Trojan, Ecce Aslan, Dorota Kusior, Małgorzata Lasota, Claire Lenouvel, Joanna Dulińska-Litewka
Multiple myeloma (MM) is characterized as a clonal expansion of malignant plasma cells in the bone marrow, which is often associated with pancytopenia and osteolytic bone disease. Interestingly, myeloma-infiltrated bone marrow is considered to be hypoxic, providing selection pressure for a developing tumour. Since HSP90 was shown to participate in stabilization of the subunit of the key transcription factor HIF-1, which controls the hypoxic response, the aim of this study was to investigate the influence of a HSP90 inhibitor 17-Allylamino-17-demethoxygeldanamycin (17-AAG), on MM cells cultured under low oxygenation conditions...
March 15, 2018: Acta Biochimica Polonica
Jeffrey D Bryant, Michael C Brown, Mikhail I Dobrikov, Elena Y Dobrikova, Sarah L Gemberling, Qing Zhang, Matthias Gromeier
Death associated protein 5 (DAP5) is an atypical isoform of the translation initiation scaffolds eukaryotic initiation factors 4GI and II (eIF4GI/II), which recruit mRNAs to ribosomes in mammals. Unlike eIF4GI/II, DAP5 binds eIF2β, a subunit of the eIF2 complex that delivers methionyl-tRNA to ribosomes. We discovered that DAP5:eIF2β binding depends on specific stimuli, e.g. protein kinase C (PKC)-Raf-ERK1/2 signals, and determines DAP5's influence on global and template-specific translation. DAP5 depletion caused an unanticipated surge of hypoxia-inducible factor 1α (HIF-1α), the transcription factor and master switch of the hypoxia response...
March 12, 2018: Molecular and Cellular Biology
Xu Chen, Xuan Li, Wenyan Zhang, Jie He, Bo Xu, Bin Lei, Zhenhua Wang, Courtney Cates, Thomas Rousselle, Ji Li
BACKGROUND: AMP-activated Protein Kinase (AMPK) is a stress-activated kinase that protects against cardiomyocyte injury during ischemia and reperfusion. c-Jun N-terminal kinase (JNK), a mitogen activated protein kinase, is activated by ischemia and reperfusion. NF-κB is an important transcription factor involved in ischemia and reperfusion injury. METHODS AND RESULTS: The intrinsic activation of AMPK attenuates the inflammation which occurred during ischemia/reperfusion through the modulation of the JNK mediated NF-κB signaling pathway...
March 8, 2018: Metabolism: Clinical and Experimental
Robert Carlsson, Ilknur Özen, Marco Barbariga, Abderahim Gaceb, Michaela Roth, Gesine Paul
Brain pericytes are important to maintain vascular integrity of the neurovascular unit under both physiological and ischemic conditions. Ischemic stroke is known to induce an inflammatory and hypoxic response due to the lack of oxygen and glucose in the brain tissue. How this early response to ischemia is molecularly regulated in pericytes is largely unknown and may be of importance for future therapeutic targets. Here we evaluate the transcriptional responses in in vitro cultured human brain pericytes after oxygen and/or glucose deprivation...
2018: PloS One
Christine Brütting, Harini Narasimhan, Frank Hoffmann, Malte E Kornhuber, Martin S Staege, Alexander Emmer
Human endogenous retroviruses (ERVs) have been found to be associated with different diseases, e.g., multiple sclerosis (MS). Most human ERVs integrated in our genome are not competent to replicate and these sequences are presumably silent. However, transcription of human ERVs can be reactivated, e.g., by hypoxia. Interestingly, MS has been linked to hypoxia since decades. As some patterns of demyelination are similar to white matter ischemia, hypoxic damage is discussed. Therefore, we are interested in the association between hypoxia and ERVs...
2018: Frontiers in Microbiology
Yanjiao Li, Li Li, Zhengjiang Qian, Boya Lin, Jidong Chen, Yixuan Luo, Junle Qu, J Usha Raj, Deming Gou
BACKGROUND: Platelet-derived growth factor BB, a potent mitogen of pulmonary artery smooth muscle cells (PASMCs), has been implicated in pulmonary arterial remodeling, which is a key pathogenic feature of pulmonary arterial hypertension. Previous microRNA profiling in platelet-derived growth factor BB-treated PASMCs found a significantly downregulated microRNA, miR-1281, but it has not been associated with any cellular function, and we investigated the possibility. METHODS AND RESULTS: Real-time quantitative reverse transcription-polymerase chain reaction assay proved that downregulation of miR-1281 was a conserved phenomenon in human and rat PASMCs...
March 7, 2018: Journal of the American Heart Association
Benjamin H Hudson, Andrew T Hale, Ryan P Irving, Shenglan Li, John D York
Sulfur assimilation is an evolutionarily conserved pathway that plays an essential role in cellular and metabolic processes, including sulfation, amino acid biosynthesis, and organismal development. We report that loss of a key enzymatic component of the pathway, bisphosphate 3'-nucleotidase (Bpnt1), in mice, both whole animal and intestine-specific, leads to iron-deficiency anemia. Analysis of mutant enterocytes demonstrates that modulation of their substrate 3'-phosphoadenosine 5'-phosphate (PAP) influences levels of key iron homeostasis factors involved in dietary iron reduction, import and transport, that in part mimic those reported for the loss of hypoxic-induced transcription factor, HIF-2α...
March 5, 2018: Proceedings of the National Academy of Sciences of the United States of America
Saki Kaneko, Chiaki Sato, Nobuya Shiozawa, Ayami Sato, Hiromi Sato, Nantiga Virgona, Tomohiro Yano
BACKGROUND/AIM: A hallmark of the progression of prostate cancer to advanced disease is the acquisition of androgen-independent growth. This malignant phenotype is characterized by resistance to conventional treatments and predisposes to formation of hypoxic regions containing stem-like cancer cells. Unfortunately, an effective therapy to target prostate cancer stem cells under hypoxia has not yet been established. In this report, we studied whether δ-tocotrienol (T3), a vitamin E family member that has exhibited the most potent anti-cancer activity, could suppress the survival of prostate cancer stem-like cells...
March 2018: Anticancer Research
Stefano Motta, Claudia Minici, Dario Corrada, Laura Bonati, Alessandro Pandini
Hypoxia inducible factors (HIFs) are transcription factors belonging to the basic helix-loop-helix PER-ARNT-SIM (bHLH-PAS) protein family with a role in sensing oxygen levels in the cell. Under hypoxia, the HIF-α degradation pathway is blocked and dimerization with the aryl hydrocarbon receptor nuclear translocator (ARNT) makes HIF-α transcriptionally active. Due to the common hypoxic environment of tumors, inhibition of this mechanism by destabilization of HIF-α:ARNT dimerization has been proposed as a promising therapeutic strategy...
February 28, 2018: PLoS Computational Biology
Zhong-Guo Fan, Xin-Liang Qu, Peng Chu, Ya-Li Gao, Xiao-Fei Gao, Shao-Liang Chen, Nai-Liang Tian
MicroRNA-210 (miRNA-210) has been reported to be associated with angiogenesis and may serve important roles in acute myocardial infarction (AMI), which remain unclear. The present study sought to evaluate the efficacy of miRNA‑210 in AMI and to examine the potential associated mechanisms. AMI models were established in Sprague‑Dawley rats. The expression of miRNA‑210 was upregulated via transfection with lentivirus‑mediated agonists and quantitative analysis was performed using the reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR)...
February 20, 2018: Molecular Medicine Reports
Robert B Jones, Kaitlyn A Dorsett, Anita B Hjelmeland, Susan L Bellis
Aberrant cell surface glycosylation is prevalent in tumor cells, and there is ample evidence that glycans have functional roles in carcinogenesis. Nonetheless, many molecular details remain unclear. Tumor cells frequently exhibit increased α2-6 sialylation on N-glycans, a modification that is added by the ST6Gal-I sialyltransferase, and emerging evidence suggests that ST6Gal-I-mediated sialylation promotes the survival of tumor cells exposed to various cell stressors. Here we report that ST6Gal-I protects cancer cells from hypoxic stress...
February 23, 2018: Journal of Biological Chemistry
Ji Kui Peng, Shi Qiang Shen, Ju Wang, Hong Wei Jiang, Yong Qiang Wang
Hypoxia is a common characteristic of solid tumors. Previous studies have reported that the tumor invasion-associated factor, AMPK-related protein kinase 5 (ARK5), is associated with a poor prognosis in colon cancer. However, whether or not ARK5 is involved in hypoxia is unclear. The aim of present study was to investigate the association between the expression of ARK5 and that of hypoxia-inducible factor 1-α (HIF1-α). Samples from 60 patients with colon cancer were collected and immunohistochemistry was used to detect the expression of ARK5 and HIF1-α within them...
March 2018: Oncology Letters
Malte Kölling, Celina Genschel, Tamas Kaucsar, Anika Hübner, Song Rong, Roland Schmitt, Inga Sörensen-Zender, George Haddad, Andreas Kistler, Harald Seeger, Jan T Kielstein, Danilo Fliser, Hermann Haller, Rudolf Wüthrich, Martin Zörnig, Thomas Thum, Johan Lorenzen
Renal ischemia-reperfusion (I/R) injury is a major cause of acute kidney injury (AKI). Non-coding RNAs are crucially involved in its pathophysiology. We identified hypoxia-induced long non-coding RNA Malat1 (Metastasis Associated Lung Adenocarcinoma Transcript 1) to be upregulated in renal I/R injury. We here elucidated the functional role of Malat1 in vitro and its potential contribution to kidney injury in vivo. Malat1 was upregulated in kidney biopsies and plasma of patients with AKI, in murine hypoxic kidney tissue as well as in cultured and ex vivo sorted hypoxic endothelial cells and tubular epithelial cells...
February 21, 2018: Scientific Reports
Hideaki Nakamura, Hidemasa Bono, Keiko Hiyama, Takeshi Kawamoto, Yukio Kato, Takeshi Nakanishi, Masahiko Nishiyama, Eiso Hiyama, Nobuyuki Hirohashi, Eisaburo Sueoka, Lorenz Poellinger, Keiji Tanimoto
Tumor hypoxia contributes to a biologically aggressive phenotype and therapeutic resistance. Recent studies have revealed that hypoxia reduces expression of several DNA damage recognition and repair (DRR) genes via both hypoxia-inducible factor (HIF)-independent and -dependent pathways, and this induced genomic instability in cancer cells. We show here that one of the HIF-target genes-differentiated embryo chondrocyte (DEC)-plays a role in DNA damage response via transcriptional repression. Comprehensive gene expression and database analyses have revealed systemic repression of DNA-DRR genes in cancer and non-cancer cells under hypoxic conditions...
2018: PloS One
Claire M Robinson, Francois Lefebvre, Betty P Poon, Aurelie Bousard, Xiaojun Fan, Mark Lathrop, Jorg Tost, William Y Kim, Yasser Riazalhosseini, Michael Ohh
In clear-cell renal cell carcinoma (ccRCC), loss of von Hippel-Lindau (VHL) tumour suppressor gene and reduced oxygen tension promote stabilisation of hypoxia-inducible factor (HIF) family of transcription factors, which promote changes in the expression of genes that contribute to oncogenesis. Multiple studies have demonstrated significant perturbations in DNA methylation in ccRCC via largely unclear mechanisms that modify the transcriptional output of tumour cells. Here, we show that the methylation status of the CpG dinucleotide within the consensus hypoxia-responsive element (HRE) markedly influences the binding of HIF and that the loss of VHL results in significant alterations in the DNA methylome...
February 20, 2018: Scientific Reports
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