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hypoxic transcription factor

Chengxing Zhu, Jiong Yu, Qiaoling Pan, Jinfeng Yang, Guangshu Hao, Yingjie Wang, Lanjuan Li, Hongcui Cao
Human placenta-derived mesenchymal stem cells (hPMSCs) reside in a physiologically low-oxygen microenvironment. Hypoxia influences a variety of stem cell cellular activities, frequently involving hypoxia-inducible factor-2 alpha (HIF-2α). This research showed that hPMSCs cultured in hypoxic conditions (5% O2) exhibited a more naïve morphology and had a higher proliferative capability and higher HIF-2α expression than hPMSCs cultured in normoxic conditions (21% O2). Similar to the hypoxic cultures, hPMSCs over-expressing HIF-2α showed higher proliferative potential and higher expression of CCND1 (CyclinD1), MYC (c-Myc), POU5F1 (Oct4) and the components of the MAPK/ERK pathway...
October 21, 2016: Scientific Reports
Ying Li Gu, Guan Qun Gao, Ning Ma, Lin Lin Ye, Li Wei Zhang, Xu Gao, Zhuo Bo Zhang
The aim of the present study was to investigate whether ciliary neurotrophic factor (CNTF) plays its neuroprotective role following hypoxic injury through the activation of signal transducer and activator of transcription 3 (STAT3) signaling. Firstly, to determine whether CNTF exerts its effects via STAT3 following hypoxic injury, cultured neurons from the cerebral cortex of mice were prepared and a neuronal model of hypoxia was then established. The neurons exposed to hypoxia were then pre-treated with CNTF and transfected with small interference RNA (siRNA) targeting STAT3 (STAT3 siRNA) using polybrene, or with STAT3Tyr705 mutant or STAT3Ser727 mutant using an electroporation system...
October 13, 2016: International Journal of Molecular Medicine
Kristy Zera, Rebecca Sweet, Jason Zastre
Ensuring continuous intracellular supply of thiamine is essential to maintain metabolism. Cellular homeostasis requires the function of the membrane bound thiamine transporters THTR1 and THTR2. In the absence of increased dietary intake of thiamine, varying intracellular levels to meet metabolic demands during pathophysiological stressors, such as hypoxia, requires adaptive regulatory mechanisms to increase thiamine transport capacity. Previous work has established the up-regulation of SLC19A3 (THTR2) gene expression and activity during hypoxic stress through the activity of the hypoxia inducible transcription factor 1 alpha (HIF-1α)...
October 12, 2016: Gene
Prabhaker Yadav, Ratnesh K Tripathi, Rajeev K Singh, Vindhya Mohindra
During the investigation of genes involved in the hypoxia tolerance, novel transcript, Replication Termination Factor 2 homologue (RTF2h), was found to be differentially expressed in brain of Clarias magur (previous name, C. batrachus) whose function was still undefined. Thus, present study was aimed to examine the transcriptional response of novel RTF2h gene, for its possible involvement in hypoxia tolerance in C. magur. Novel transcripts expressed under hypoxic stress were identified from ESTs obtained from SSH libraries of C...
October 14, 2016: Molecular Biology Reports
Natasha M Rogers, Maryam Sharifi-Sanjani, Mingyi Yao, Kedar Ghimire, Raquel Bienes-Martinez, Stephanie M Mutchler, Heather E Knupp, Jeffrey Baust, Enrico M Novelli, Mark Ross, Claudette St Croix, Johannes C Kutten, Caitlin A Czajka, John C Sembrat, Mauricio Rojas, David Labrousse-Arias, Timothy N Bachman, Rebecca R Vanderpool, Brian S Zuckerbraun, Hunter C Champion, Ana L Mora, Adam C Straub, Richard A Bilonick, Maria J Calzada, Jeffrey S Isenberg
AIMS: Thrombospondin-1 (TSP1) is a ligand for CD47 and TSP1(-/-) mice are protected from pulmonary hypertension (PH). We hypothesized the TSP1-CD47 axis is upregulated in human PH and promotes pulmonary arterial vasculopathy. METHODS AND RESULTS: We analyzed the molecular signature and functional response of lung tissue and distal pulmonary arteries (PAs) from individuals with (n=23) and without (n=16) PH. Compared to controls, lungs and distal PAs from PH patients showed induction of TSP1-CD47 and endothelin-1/endothelin A receptor (ET-1/ETA) protein and mRNA...
October 13, 2016: Cardiovascular Research
Nathalie Dehne, Bernhard Brüne
Hypoxia, by activating transcription factors induces transcription of some genes but it also reduces mRNA synthesis by mechanisms that are poorly defined. Activation of human macrophages with interleukin (IL)-4 showed that up-regulation of some IL-4 target genes was reduced when macrophages were incubated at 1% oxygen. Hypoxia impaired induction of chemokine (C-C motif) ligand 18 (CCL18), although IL-4-induced DNA binding of the transcription factor STAT6 remained intact. In contrast, induction of serine peptidase inhibitor, Kunitz type (SPINT)2, another IL-4/STAT6 target gene, was not affected by hypoxia...
October 11, 2016: Biochimica et Biophysica Acta
Divya Ramchandani, Dusten Unruh, Clayton S Lewis, Vladimir Y Bogdanov, Georg F Weber
Molecules of the coagulation pathway predispose patients to cancer-associated thrombosis and also trigger intracellular signaling pathways that promote cancer progression. The primary transcript of tissue factor, the main physiologic trigger of blood clotting, can undergo alternative splicing yielding a secreted variant, termed asTF (alternatively spliced tissue factor). asTF is not required for normal hemostasis, but its expression levels positively correlate with advanced tumor stages in several cancers, including pancreatic adenocarcinoma...
October 10, 2016: Laboratory Investigation; a Journal of Technical Methods and Pathology
Juwen C DuBois, A George Smulian
The Histoplasma capsulatum sterol regulatory element binding protein (SREBP), Srb1 is a member of the basic helix-loop-helix (bHLH), leucine zipper DNA binding protein family of transcription factors that possess a unique tyrosine (Y) residue instead of an arginine (R) residue in the bHLH region. We have determined that Srb1 message levels increase in a time dependent manner during growth under oxygen deprivation (hypoxia). To further understand the role of Srb1 during infection and hypoxia, we silenced the gene encoding Srb1 using RNA interference (RNAi); characterized the resulting phenotype, determined its response to hypoxia, and its ability to cause disease within an infected host...
2016: PloS One
Jian-Li Gao, Yan-Mei Shui, Wei Jiang, En-Yi Huang, Qi-Yang Shou, Xin Ji, Bai-Cheng He, Gui-Yuan Lv, Tong-Chuan He
Hypoxic in the tumor mass is leading to the myeloproliferative-like disease (leukemoid reaction) and anemia of body, which characterized by strong extensive extramedullary hematopoiesis (EMH) in spleen. As the key transcription factor of hypoxia, hypoxia-inducible factor-1 (HIF-1) activates the expression of genes essential for EMH processes including enhanced blood cell production and angiogenesis. We found ursolic acid (UA), a natural pentacyclic triterpenoid carboxylic acid, inhibited growth of breast cancer both in vivo and in vitro...
September 30, 2016: Oncotarget
Hirak Biswas, Gregory D Longmore
Hypoxic injury to the heart results in cardiac fibrosis that leads to cardiac dysfunction and heart failure. SNAIL1 is a zinc finger transcription factor implicated in fibrosis following organ injury and cancer. To determine if the action of SNAIL1 contributed to cardiac fibrosis following hypoxic injury, we used an endogenous SNAIL1 bioluminescence reporter mice, and SNAIL1 knockout mouse models. Here we report that SNAIL1 expression is upregulated in the infarcted heart, especially in the myofibroblasts. Utilizing primary cardiac fibroblasts in ex vivo cultures we find that pro-fibrotic factors and collagen I increase SNAIL1 protein level...
2016: PloS One
Daniele M Gilkes
Most solid tumors contain regions of hypoxia in which increased cell proliferation promotes increased oxygen consumption and the condition is further exacerbated as cancer cells become localized far from a functional blood vessel, further decreasing the oxygen supply. An important mechanism that promotes cell adaptation to hypoxic conditions is the expression of hypoxia-inducible factors (HIFs). Hypoxia-inducible factors transcriptionally regulate many genes involved in the invasion and metastasis of breast cancer cells...
September 30, 2016: International Journal of Molecular Sciences
Brittany Barreto, Elizabeth Rogers, Jun Xia, Ryan L Frisch, Megan Richters, Devon M Fitzgerald, Susan M Rosenberg
: Microbes and human cells possess mechanisms of mutagenesis activated by stress responses. Stress-inducible mutagenesis mechanisms may provide important models for mutagenesis that drives host-pathogen interactions, antibiotic resistance, and possibly much of evolution generally. In Escherichia coli, repair of DNA double-strand breaks is switched to a mutagenic mode, using error-prone DNA polymerases, via the SOS DNA-damage and the general (σ(S)) stress responses. We investigated small RNA (sRNA) clients of Hfq, an RNA chaperone that promotes mutagenic break repair (MBR), and found that GcvB promotes MBR by allowing a robust σ(S) response, achieved via opposing the membrane stress (σ(E)) response...
October 3, 2016: Journal of Bacteriology
Masaru Koido, Junko Sakurai, Satomi Tsukahara, Yuri Tani, Akihiro Tomida
Prostate transmembrane protein, androgen induced 1 (PMEPA1) is highly expressed in various solid tumors and is known to play important roles in the transforming growth factor-β (TGF-β) signaling pathway. Here, we demonstrate a novel relationship between PMEPA1 and hypoxia, a common microenvironmental stress condition in solid tumors. We showed that induction of PMEPA1 expression occurred during hypoxia in a manner dependent on both TGF-β signaling and hypoxia-inducible factor-1 (HIF-1) pathways. Furthermore, overexpression and knockdown experiments revealed that PMEPA1 enhanced HIF-1 transcription activity...
October 28, 2016: Biochemical and Biophysical Research Communications
Hongbao Liu, Binya Shi, Yu Yan, Ligang Niu, Yuhui Zhou, Hui Cai, Guanqun Ge
Breast cancer side population (SP) cells display distinctly higher CXCR4 and ABCG2 expression levels, sphere formation efficiency (SFE), and growth capacity, even under hypoxic conditions. Inhibition of CXCR4 by the inhibitor AMD3100 suppressed SFE and cell growth under hypoxia. ABCG2 confers the major phenotype of SP cells, and knockdown of ABCG2 also suppressed SFE and the growth of hypoxic SP cells. In addition, we found that CXCR4 promoted the expression of c-Jun, a putative transcription factor for ABCG2...
September 30, 2016: Oncology Research
Andres A Urrutia, Aqeela Afzal, Jacob Nelson, Olena Davidoff, Kenneth W Gross, Volker H Haase
A classic response to systemic hypoxia is the increased production of red blood cells due to hypoxia-inducible factor (HIF)-mediated induction of erythropoietin (EPO). EPO is a glycoprotein hormone that is essential for normal erythropoiesis and is predominantly synthesized by peritubular renal interstitial fibroblast-like cells, which express cellular markers characteristic of neuronal cells and pericytes. To investigate whether the ability to synthesize EPO is a general functional feature of pericytes, we used conditional gene targeting to examine the von Hippel-Lindau (VHL) / prolyl-4-hydroxylase domain (PHD) / HIF axis in cell expressing neural glial antigen 2 (NG2), a known molecular marker of pericytes in multiple organs...
September 28, 2016: Blood
T G Demarest, R A Schuh, E L Waite, J Waddell, M C McKenna, Gary Fiskum
Males are more susceptible to brain mitochondrial bioenergetic dysfunction following neonatal cerebral hypoxic-ischemia (HI) than females. Mitochondrial biogenesis has been implicated in the cellular response to HI injury, but sex differences in biogenesis following HI have not been described. We tested the hypothesis that mitochondrial biogenesis or the expression of mitochondrial electron transport chain (ETC) proteins are differentially stimulated in the brains of 8 day old male and female rats one day following HI, and promoted by treatment with acetyl-L-carnitine (ALCAR)...
September 28, 2016: Journal of Bioenergetics and Biomembranes
Hiroki Daijo, Yuma Hoshino, Shinichi Kai, Kengo Suzuki, Kenichiro Nishi, Yoshiyuki Matsuo, Hiroshi Harada, Kiichi Hirota
Cigarette smoke (CS) is a major contributor to the development of a large number of fatal and debilitating disorders. However, the precise molecular mechanisms underlying the effects of CS in lung disease are largely unknown. To elucidate these pathophysiological processes, we examined the in vitro and in vivo effects of CS extract (CSE) and CS on the transcription factor, hypoxia-inducible factor 1 (HIF-1). CSE induced concentration- and time-dependent accumulation of HIF-1α protein in human lung epithelial-like cells under non-hypoxic conditions...
September 29, 2016: Scientific Reports
Yu Di, Yiou Zhang, Linping Hui, Hongwei Yang, Yang Yang, Aiyuan Wang, Xiaolong Chen
Hypoxia is a key factor in the pathogenesis of angiogenesis, and cysteine‑rich 61 (CCN1), an angiogenic factor, is involved in the development of pathological angiogenesis. The aim of the present study was to investigate the mechanism of CCN1 RNA interference (RNAi)‑induced inhibition of hypoxia‑induced pathological angiogenesis in endothelial cells. Human umbilical vein endothelial cells (HUVECs) were cultured under hypoxic conditions in vitro. The effects of inhibiting phosphoinositide 3‑kinase (PI3K)/Akt signaling using LY294002 were investigated in hypoxic HUVECs...
September 26, 2016: Molecular Medicine Reports
Qiang Li, Rui Liu, Jianmin Zhao, Quanli Lu
Ischemic-hypoxic condition for local osteoblasts and bone mesenchymal stem cells during bone fracture inhibits bone repairing. N-methyl pyrrolidone (NMP) has been approved as a safe and biologically inactive small chemical molecule, and might be useful for bone fracture repairing. In the present study, we investigated the effect of NMP on the hypoxia-reduced cellular viability and the expression of differentiation-associated markers, such as bone morphogenetic protein 2 (BMP-2), propeptide of type I procollagen I (PINP), alkaline phosphatase (ALP) or runt-related transcription factor 2 (Runx2) in the osteoblasts, and then we examined the molecular mechanism underlining such effect in the human osteoblastic hFOB 1...
2016: Journal of Toxicological Sciences
Qun Cai, Ting Wang, Wen-Jie Yang, Xing Fen
Hypoxic injuries during fetal distress have been shown to cause reduced expression of microRNA-27a (miR-27a), which regulates sensitivity of cortical neurons to apoptosis. We hypothesized that miR-27a overexpression attenuates hypoxia- and ischemia-induced neuronal apoptosis by regulating FOXO1, an important transcription factor for regulating the oxidative stress response. miR-27a mimic was transfected into hippocampal neurons to overexpress miR-27a. Results showed increased hippocampal neuronal viability and decreased caspase-3 expression...
August 2016: Neural Regeneration Research
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