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Hypoxia induced factor

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https://www.readbyqxmd.com/read/28548959/identification-of-the-histone-lysine-demethylase-kdm4a-jmjd2a-as-a-novel-epigenetic-target-in-m1-macrophage-polarization-induced-by-oxidized-ldl
#1
Xue Wang, Siqing Wang, Gang Yao, Dehai Yu, Kexin Chen, Qian Tong, Long Ye, Chuan Wu, Yue Sun, Haixia Li, Dirk M Hermann, Thorsten R Döppner, Fengyan Jin, Yun Dai, Jiang Wu
Oxidized low density lipoprotein (oxLDL) induces macrophage activation, an event essential for atherosclerosis. Emerging evidence supports that epigenetic regulation plays important roles in macrophage activation and function. However, it remains unclear which epigenetic modulator is responsible for oxLDL-induced macrophage activation. Here, we identify for the first time KDM4A (JMJD2A) as an epigenetic modifying enzyme that controls oxLDL-induced pro-inflammatory M1 polarization of macrophages. OxLDL triggered M1 polarization of murine and human macrophages, characterized by expression of iNOS and robust production of inflammatory cytokines (e...
May 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/28546582/control-of-amino-acid-transport-coordinates-metabolic-reprogramming-in-t-cell-malignancy
#2
K M Grzes, M Swamy, J L Hukelmann, E Emslie, L V Sinclair, D A Cantrell
This study explores the regulation and importance of System L amino acid transport in a murine model of T cell acute lymphoblastic leukemia (T-ALL) caused by deletion of phosphatase and tensin homologue deleted on chromosome 10 (PTEN). There has been a strong focus on glucose transport in leukemias but the present data show that primary T-ALL cells have increased transport of multiple nutrients. Specifically, increased leucine transport in T-ALL fuels mammalian target of rapamycin complex 1 (mTORC1) activity which then sustains expression of hypoxia inducible factor-1α (HIF1α) and c-Myc; drivers of glucose metabolism in T cells...
May 26, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28546124/stressor-driven-extracellular-acidosis-as-tumor-inducer-via-aberrant-enzyme-activation-a-review-on-the-mechanisms-and-possible-prophylaxis
#3
REVIEW
Seema Patel
When the extracellular pH of the human body vacillates in either direction, tissue homeostasis is compromised. Fluctuations in acidosis have been linked to a wide variety of pathological conditions, including bone loss, cancer, allergies, and auto-immune diseases. Stress conditions may affect oxygen tension and hypoxia modulates the expression and/or activity of membrane tethered transporters/pumps, transcription factors, enzymes and intercellular junctions. These modifications provoke erratic gene expression, aberrant tissue remodeling and oncogenesis...
May 22, 2017: Gene
https://www.readbyqxmd.com/read/28545523/l-mimosine-and-hypoxia-can-increase-angiogenin-production-in-dental-pulp-derived-cells
#4
Klara Janjić, Michael Edelmayer, Andreas Moritz, Hermann Agis
BACKGROUND: Angiogenin is a key molecule in the healing process which has been successfully applied in the field of regenerative medicine. The role of angiogenin in dental pulp regeneration is unclear. Here we aimed to reveal the impact of the hypoxia mimetic agent L-mimosine (L-MIM) and hypoxia on angiogenin in the dental pulp. METHODS: Human dental pulp-derived cells (DPC) were cultured in monolayer and spheroid cultures and treated with L-MIM or hypoxia. In addition, tooth slice organ cultures were applied to mimic the pulp-dentin complex...
May 25, 2017: BMC Oral Health
https://www.readbyqxmd.com/read/28545512/tie2-as-a-novel-key-factor-of-microangiopathy-in-systemic-sclerosis
#5
Falk Moritz, Janine Schniering, Jörg H W Distler, Renate E Gay, Steffen Gay, Oliver Distler, Britta Maurer
BACKGROUND: The angiopoietin(Ang)/Tie2 system is a key regulator of vascular biology. The expression of membrane bound (mb) Tie2 and Ang-1 ensures vessel stability, whereas Ang-2, inducible by vascular endothelial growth factor (VEGF), hypoxia, and inflammation, acts as an antagonist. Tie2 signalling is also attenuated by soluble Tie2 (sTie2), the extracellular domain of the receptor, which is shed upon stimulation with VEGF. Herein, we investigate the role of Ang/Tie2 in the peripheral vasculopathy in systemic sclerosis (SSc) including animal models...
May 25, 2017: Arthritis Research & Therapy
https://www.readbyqxmd.com/read/28544376/hif-2%C3%AE-regulates-non-canonical-glutamine-metabolism-via-activation-of-pi3k-mtorc2-pathway-in-human-pancreatic-ductal-adenocarcinoma
#6
Wenzhu Li, Changhao Chen, Xiaohui Zhao, Huilin Ye, Yue Zhao, Zhiqiang Fu, Wenwei Pan, Shangyou Zheng, Lusheng Wei, Tianwen Nong, Zhihua Li, Rufu Chen
Hypoxia-inducible factor-2α (HIF-2α) plays an important role in increasing cancer progression and distant metastasis in a variety of tumour types. We aimed to investigate its biological function and clinical significance in human pancreatic ductal adenocarcinoma (PDAC). A total of 283 paired PDAC tissues and adjacent normal tissues were collected from patients who underwent surgery or biopsy at Sun Yat-sen Memorial Hospital between February 2004 and October 2016. In this study, we noted that HIF-2α expression was significantly up-regulated in PDAC, positively associated with disease stage, lymph-node metastasis and patient survival, and identified as an independent prognostic factor of PDAC patients...
May 24, 2017: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/28543639/lncrna-rp11-296a18-3-mir-138-hif1a-pathway-regulates-the-proliferation-ecm-synthesis-of-human-nucleus-pulposus-cells-hnpcs-%C3%A2
#7
Xiaobin Wang, Guohua Lv, Jing Li, Bing Wang, Qianshi Zhang, Chang Lu
BACKGROUND: During the process of Intervertebral disc degeneration (IDD), nucleus pulposus apoptosis increases, extracellular matrix (ECM) alters and/or degrades, abnormal proliferation of cells forms cell clusters, and the expression of various inflammatory factors increases. Thus, regulation of human nucleus pulposus cell (HNPC) proliferation and ECM synthesis present promising strategies for IDD treatment. Accumulating evidence indicates that non-coding RNAs are involved in various cellular processes, including cell proliferation, differentiation, apoptosis and metastasis...
May 24, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28543362/commd1-a-multifunctional-regulatory-protein
#8
Mario Riera Romo
The COMMD Protein Family is highly conserved among multicellular eukaryotic organisms and many orthologs of human COMMD genes have been found in different species of plants, invertebrates, lower vertebrates and mammals. COMMD1 is the best characterized member of the family and is conserved among vertebrates. This protein represents a pleiotropic factor involved in the regulation of many cellular and physiological processes that include copper and cholesterol homeostasis, ionic transport, oxidative stress, protein aggregation, protein trafficking, NF-κB-mediated transcription, hypoxia induced transcription, DNA damage response and oncogenesis...
May 20, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28542591/molecular-characterization-of-mudskipper-boleophthalmus-pectinirostris-hypoxia-inducible-factor-1%C3%AE-hif-1%C3%AE-and-analysis-of-its-function-in-monocytes-macrophages
#9
Feng Guan, Xin-Jiang Lu, Chang-Hong Li, Jiong Chen
Hypoxia-inducible factor-1α (HIF-1α) plays a critical role in immune and inflammatory responses and is important in controlling a variety of processes in monocytes and macrophages. However, very little information is available about the functions of HIF-1α in fish monocytes/macrophages (MO/MФ). In this study, the cDNA sequence of the mudskipper (Boleophthalmus pectinirostris) HIF-1α gene (BpHIF-1α) was determined. Sequence comparison and phylogenetic tree analysis showed that BpHIF-1α is clustered in the fish HIF-1α tree...
2017: PloS One
https://www.readbyqxmd.com/read/28542352/preconditioning-of-adipose-tissue-derived-mesenchymal-stem-cells-with-deferoxamine-increases-the-production-of-pro-angiogenic-neuroprotective-and-anti-inflammatory-factors-potential-application-in-the-treatment-of-diabetic-neuropathy
#10
Carolina Oses, Belén Olivares, Marcelo Ezquer, Cristian Acosta, Paul Bosch, Macarena Donoso, Patricio Léniz, Fernando Ezquer
Diabetic neuropathy (DN) is one of the most frequent and troublesome complications of diabetes mellitus. Evidence from diabetic animal models and diabetic patients suggests that reduced availability of neuroprotective and pro-angiogenic factors in the nerves in combination with a chronic pro-inflammatory microenvironment and high level of oxidative stress, contribute to the pathogenesis of DN. Mesenchymal stem cells (MSCs) are of great interest as therapeutic agents for regenerative purposes, since they can secrete a broad range of cytoprotective and anti-inflammatory factors...
2017: PloS One
https://www.readbyqxmd.com/read/28542038/hypoxia-as-a-target-for-drug-combination-therapy-of-liver-cancer
#11
Cressida Bowyer, Andrew L Lewis, Andrew W Lloyd, Gary J Phillips, Wendy M Macfarlane
Hepatocellular carcinoma (HCC) is the third most frequent cause of cancer deaths worldwide. The standard of care for intermediate HCC is transarterial chemoembolization, which combines tumour embolization with locoregional delivery of the chemotherapeutic doxorubicin. Embolization therapies induce hypoxia, leading to the escape and proliferation of hypoxia-adapted cancer cells. The transcription factor that orchestrates responses to hypoxia is hypoxia-inducible factor 1 (HIF-1). The aim of this work is to show that targeting HIF-1 with combined drug therapy presents an opportunity for improving outcomes for HCC treatment...
May 24, 2017: Anti-cancer Drugs
https://www.readbyqxmd.com/read/28539891/double-knockdown-of-phd1-and-keap1-attenuated-hypoxia-induced-injuries-in-hepatocytes
#12
Jing Liu, Yiping Li, Lei Liu, Zhi Wang, Chuanbing Shi, Zhengyuan Cheng, Xiaoyi Zhang, Fengan Ding, Ping Sheng Chen
Background and Aims: Hypoxia and oxidative stress contribute toward liver fibrosis. In this experiment, we used small hairpin RNA (shRNA) to interfere with the intracellular oxygen sensor-prolyl hydroxylase 1 (PHD1) and the intracellular oxidative stress sensor-kelch-like ECH associated protein 1 (Keap1) in the hypoxic hepatocytes in order to investigate the function of PHD1and Keap1. Methods: We first established the CCl4-induced liver fibrosis model, subsequently, the levels of the PHD1, hypoxia-inducible factor-1α (HIF-1α), hypoxia-inducible factor-2α (HIF-2α), Keap1, and nuclear factor-erythroid 2 p45-related factor 2 (Nrf2) were detected in liver tissues...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/28539353/crf-and-urocortin-3-protect-the-heart-from-hypoxia-reoxygenation-induced-apoptosis-in-zebrafish
#13
Tegan A Williams, Jillian C Bergstrome, Juliana Scott, Nicholas J Bernier
Fish routinely experience environmental hypoxia and have evolved various strategies to tolerate this challenge. Given the key role of the corticotropin-releasing factor (CRF) system in coordinating the response to stressors and its cardioprotective actions against ischemia in mammals, we sought to characterize the cardiac CRF system in zebrafish and its role in hypoxia tolerance. We established that all genes of the CRF system, the ligands CRFa, CRFb, urotensin 1 (UTS1) and urocortin 3 (UCN3), the two receptor subtypes (CRFR1 and CRFR2), and the binding protein (CRFBP) are expressed in the heart of zebrafish: crfr1 > crfr2 = crfbp > crfa > ucn3 > crfb > uts1...
May 24, 2017: American Journal of Physiology. Regulatory, Integrative and Comparative Physiology
https://www.readbyqxmd.com/read/28539339/mif-2-d-dt-enhances-proximal-tubular-cell-regeneration-through-slpi-and-atf4-dependent-mechanisms
#14
Akinobu Ochi, Dong Chen, Wibke Schulte, Lin Leng, Nickolas Gilbert Moeckel, Marta Piecychna, Luisa Averdunk, Christian Stoppe, Richard Bucala, Gilbert W Moeckel
Macrophage migration inhibitory factor (MIF) is a cytokine with pleiotropic actions that is produced by several organs and cell types. Depending on the target cell and the inflammatory context, MIF can engage its two component receptor complex CD74 and CD44, and the chemokine receptors CXCR2/4. MIF is constitutively expressed in renal proximal tubular cells, stored in intracellular preformed pools and is released at a low rate. Recently a second MIF-like protein (i.e. MIF-2/D-DT) has been characterized in mammals...
May 24, 2017: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/28538666/melatonin-attenuates-pulmonary-hypertension-in-chronically-hypoxic-rats
#15
Ming Wai Hung, Hang Mee Yeung, Chi Fai Lau, Angela Ming See Poon, George L Tipoe, Man Lung Fung
Chronic hypoxia induces pulmonary hypertension and vascular remodeling, which are clinically relevant to patients with chronic obstructive pulmonary disease (COPD) associated with a decreased level of nitric oxide (NO). Oxidative stress and inflammation play important roles in the pathophysiological processes in COPD. We examined the hypothesis that daily administration of melatonin (10 mg/kg) mitigates the pulmonary hypertension and vascular remodeling in chronically hypoxic rats. The right ventricular systolic pressure (RVSP) and the thickness of pulmonary arteriolar wall were measured from normoxic control, vehicle- and melatonin-treated hypoxic rats exposed to 10% O₂ for 14 days...
May 24, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28538016/hypoxia-inducible-factor-activation-in-diabetic-kidney-disease
#16
Patrik Persson, Fredrik Palm
PURPOSE OF REVIEW: Tissue hypoxia is present in kidneys from diabetic patients and constitutes a central pathway to diabetic kidney disease (DKD). This review summarizes regulation of hypoxia inducible factor (HIF) and interventions towards the same for treatment of DKD. RECENT FINDINGS: In the hypoxic diabetic kidney, HIF activity and the effects of HIF signaling seem to be cell-specific. In mesangial cells, elevated glucose levels induce HIF activity by a hypoxia-independent mechanism...
May 19, 2017: Current Opinion in Nephrology and Hypertension
https://www.readbyqxmd.com/read/28537846/uremic-toxins-affect-the-imbalance-of-redox-state-and-overexpression-of-prolyl-hydroxylase-2-in-human-adipose-tissue-derived-mesenchymal-stem-cells-involved-in-wound-healing
#17
Vuong Cat Khanh, Kinuko Ohneda, Toshiki Kato, Toshiharu Yamashita, Fujio Sato, Kana Tachi, Osamu Ohneda
Chronic kidney disease (CKD) results in a delay in wound healing because of its complications such as uremia, anemia, and fluid overload. Mesenchymal stem cells (MSCs) are considered to be a candidate for wound healing because of the ability to recruit many types of cells. However, it is still unclear whether the CKD-adipose tissue-derived MSCs (CKD-AT-MSCs) have the same function in wound healing as healthy donor-derived normal AT-MSCs (nAT-MSCs). In this study, we found that uremic toxins induced elevated reactive oxygen species (ROS) expression in nAT-MSCs, resulting in the reduced expression of hypoxia-inducible factor-1α (HIF-1α) under hypoxic conditions...
May 24, 2017: Stem Cells and Development
https://www.readbyqxmd.com/read/28537679/mir-15a-expression-analysis-in-non-small-cell-lung-cancer-a549-cells-under-local-hypoxia-microenvironment
#18
X-G Jing, T-F Chen, C Huang, H Wang, L An, Z Cheng, G-J Zhang
OBJECTIVE: Lung cancer is a common tumor in the clinic. Hypoxia is an important biological characteristic in the solid malignant tumor. MiRNA participates in cell proliferation, differentiation, and apoptosis. This study tested hypoxia-inducible factor 1-α (HIF-1α) in lung cancer patients and analyzed the microRNA-15a (miR-15a) expression in A549 cells under different local hypoxia microenvironments. PATIENTS AND METHODS: A total of 40 non-small cell lung cancer (NSCLC) patients in First Affiliated Hospital of Zhengzhou University between Jan 2015 and Jan 2016 were involved in this study...
May 2017: European Review for Medical and Pharmacological Sciences
https://www.readbyqxmd.com/read/28537472/a-novel-role-for-a-glycolytic-pathway-kinase-in-regulating-autophagy-has-implications-in-cancer-therapy
#19
Aileen R Ariosa, Daniel J Klionsky
When it comes to cancer initiation and progression, macroautophagy/autophagy seemingly acts in a contradictory fashion, serving either as a suppressive factor that functions to protect against tumor formation or as a support mechanism that sustains the disease itself through its cytoprotective functions. In tumor suppression, autophagy assists by restricting oxidative stress and curbing genomic instability that could possibly cause oncogenic mutations. However, in certain circumstances, autophagy can also promote cancer by providing nourishment and by limiting stress-response pathways, leading to cancer cell survival and rapid proliferation...
May 24, 2017: Autophagy
https://www.readbyqxmd.com/read/28536481/trpv4-dependent-induction-of-a-novel-mammalian-cold-inducible-protein-srsf5-as-well-as-cirp-and-rbm3
#20
Takanori Fujita, Hiroaki Higashitsuji, Hisako Higashitsuji, Yu Liu, Katsuhiko Itoh, Toshiharu Sakurai, Takahiro Kojima, Shuya Kandori, Hiroyuki Nishiyama, Motoi Fukumoto, Manabu Fukumoto, Koji Shibasaki, Jun Fujita
Cold-inducible RNA-binding protein (CIRP) and RNA-binding motif protein 3 (RBM3) are two evolutionarily conserved RNA-binding proteins that are structurally related to hnRNPs and upregulated in response to moderately low temperatures in mammalian cells. Although contributions of splicing efficiency, the gene promoters activated upon mild hypothermia and the transcription factor Sp1 to induction of CIRP have been reported, precise mechanisms by which hypothermia and other stresses induce the expression of mammalian cold-inducible proteins (CIPs) are poorly understood...
May 23, 2017: Scientific Reports
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