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https://www.readbyqxmd.com/read/28327666/hypoxia-induces-h19-expression-through-direct-and-indirect-hif-1%C3%AE-activity-promoting-oncogenic-effects-in-glioblastoma
#1
Weining Wu, Qi Hu, Er Nie, Tianfu Yu, Youzhi Wu, Tongle Zhi, Kuan Jiang, Feng Shen, Yingyi Wang, Junxia Zhang, Yongping You
H19 expression is elevated in many human tumors including glioblastomas, suggesting an oncogenic role for the long noncoding RNA; yet the upregulation of H19 in glioblastomas remains unclear. Here we report that hypoxia significantly stimulated H19 expression in glioblastoma cell lines, which was related to hypoxia-inducible factors 1α (Hif-1α). Hif-1α promoted H19 expression in U87 and U251 cells. Meanwhile PTEN is an advantageous factor to affect H19 expression, through attenuating Hif-1α stability. Hif-1α also positively correlates with H19 in human glioblastoma samples depending on PTEN status...
March 22, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28320353/genome-independent-hypoxic-repression-of-estrogen-receptor-alpha-in-breast-cancer-cells
#2
Mercè Padró, Raymond J Louie, Brian V Lananna, Adam J Krieg, Luika A Timmerman, Denise A Chan
BACKGROUND: About 75-80% of breast tumors express the estrogen receptor alpha (ER-α) and are treated with endocrine-target therapeutics, making this the premier therapeutic modality in the breast cancer clinic. However, acquired resistance is common and about 20% of resistant tumors loose ER-α expression via unknown mechanisms. Inhibition of ER-α loss could improve endocrine therapeutic efficacy, benefiting a significant number of patients. Here we test whether tumor hypoxia might commonly produce ER-α loss...
March 20, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28320281/cerebral-mechanisms-of-hypoxic-ischemic-postconditioning
#3
REVIEW
O V Vetrovoy, E A Rybnikova, M O Samoilov
This review analyzes recent data on mechanisms of cerebral hypoxia and the protective methods of hypoxic and ischemic postconditioning, as well as their interrelationship with the key mechanisms responsible for neuroprotection and neuroplasticity. Upregulation of expression of antiapoptotic factors and neurotrophins and modulation of activity of several protein kinases and transcription factors such as hypoxia-inducible factor-1 (HIF-1) are considered as the most important aspects in the neuroprotective potential of postconditioning...
March 2017: Biochemistry. Biokhimii︠a︡
https://www.readbyqxmd.com/read/28319066/nucleus-accumbens-associated-protein-1-promotes-glycolysis-and-survival-of-hypoxic-tumor-cells-via-the-hdac4-hif-1%C3%AE-axis
#4
Y Zhang, Y-J Ren, L-C Guo, C Ji, J Hu, H-H Zhang, Q-H Xu, W-D Zhu, Z-J Ming, Y-S Yuan, X Ren, J Song, J-M Yang
Nucleus accumbens-associated protein-1 (NAC1), a nuclear factor of the BTB/POZ gene family, has emerging roles in cancer. In this study, we identified the NAC1-HDAC4-HIF-1α axis as an important pathway in regulating glycolysis and hypoxic adaptation in tumor cells. We show that nuclear NAC1 binds to histone deacetylase type 4 (HDAC4), hindering phosphorylation of HDAC4 at Ser(246) and preventing its nuclear export that leads to cytoplasmic degradation of the deacetylase. Accumulation of HDAC4 in the nuclei results in an attenuation of HIF-1α acetylation, enhancing the stabilization and transcriptional activity of HIF-1α and strengthening adaptive response of cells to hypoxia...
March 20, 2017: Oncogene
https://www.readbyqxmd.com/read/28318025/maternal-chronic-hypoxia-increases-expression-of-genes-regulating-lung-liquid-movement-and-surfactant-maturation-in-male-fetuses-in-late-gestation
#5
Erin V McGillick, Sandra Orgeig, Beth J Allison, Kirsty L Brain, Youguo Niu, Nozomi Itani, Katie L Skeffington, Andrew D Kane, Emilio A Herrera, Dino A Giussani, Janna L Morrison
Chronic fetal hypoxaemia is a common pregnancy complication that may arise from maternal, placental and/or fetal factors. Respiratory outcome of the infant at birth likely depends on the duration, timing and severity of the hypoxaemic insult. We have isolated the effect of maternal chronic hypoxia (MCH) for a month in late gestation on fetal lung development. Pregnant ewes were exposed to normoxia (21% O2 ) or hypoxia (10% O2 ) from 105-138 d gestation (term ∼145 d). At 138 d, gene expression in fetal lung tissue was determined by qRT-PCR...
March 20, 2017: Journal of Physiology
https://www.readbyqxmd.com/read/28316125/deferoxamine-activated-hypoxia-inducible-factor-1-restores-cardioprotective-effects-of-sevoflurane-postconditioning-in-diabetic-rats
#6
Peng Xie, Long Yang, Ailaiti Talaiti, Jianjiang Wu, Jin Yu, Tian Yu, Haiying Wang, Bo Huang, Qin Wu, Yiliyaer Maimaitili, Jiang Wang, Haiping Ma, Yining Yang, Hong Zheng
AIM: The cardioprotective effects of sevoflurane postconditioning (SpostC) are eliminated under diabetic conditions, and the underlying mechanism for this phenomenon remains unclear. Many studies have demonstrated that the hypoxia-inducible factor-1(HIF-1) signaling pathway in the myocardium is impaired under diabetic conditions. This study was to investigate whether deferoxamine (DFO)-induced activation of HIF-1 signaling pathway can restore the cardioprotective effects of SpostC in diabetic rats...
March 17, 2017: Acta Physiologica
https://www.readbyqxmd.com/read/28314761/hypoxia-mediated-regulation-of-the-secretory-properties-of-mitral-valve-interstitial-cells
#7
Kareem Salhiyyah, Padmini Sarathchandra, Najma Latif, Magdi H Yacoub, Adrian H Chester
The sophisticated function of the mitral valve depends to a large extent on the extracellular matrix (ECM) and specific cellular components. These are tightly regulated by a repertoire of mechanical stimuli and biological pathways. One potentially important pathway is hypoxia. The purpose of this investigation is to determine the effect of hypoxia on the regulation of mitral valve interstitial cells (MVIC) with respect to the synthesis and secretion of extracellular matrix proteins. Hypoxia resulted in reduced production of total collagen and sulphated glycosaminoglycans (sGAG) in cultured porcine MVIC...
March 17, 2017: American Journal of Physiology. Heart and Circulatory Physiology
https://www.readbyqxmd.com/read/28304334/kdm2-family-members-are-regulated-by-hif-1-in-hypoxia
#8
Michael Batie, Jimena Druker, Laura D'Ignazio, Sonia Rocha
Hypoxia is not only a developmental cue but also a stress and pathological stimulus in many human diseases. The response to hypoxia at the cellular level relies on the activity of the transcription factor family, hypoxia inducible factor (HIF). HIF-1 is responsible for the acute response and transactivates a variety of genes involved in cellular metabolism, cell death, and cell growth. Here, we show that hypoxia results in increased mRNA levels for human lysine (K)-specific demethylase 2 (KDM2) family members, KDM2A and KDM2B, and also for Drosophila melanogaster KDM2, a histone and protein demethylase...
March 17, 2017: Cells
https://www.readbyqxmd.com/read/28302721/involvement-of-notch1-signaling-in-malignant-progression-of-a549-cells-subjected-to-prolonged-cadmium-exposure
#9
Kota Fujiki, Hisako Inamura, Takamitsu Miyayama, Masato Matsuoka
Cadmium exposure is known to increase lung cancer risk, but the underlying molecular mechanisms in cadmium-stimulated progression of malignancy are unclear. Here, we examined the effects of prolonged cadmium exposure on the malignant progression of A549 human lung adenocarcinoma cells and the roles of Notch1, hypoxia-inducible factor 1α (HIF-α), and insulin-like growth factor 1 receptor (IGF-1R)/Akt/extracellular signal-regulated kinase (ERK)/p70 S6 kinase 1 (S6K1) signaling pathways. Exposing A549 cells to 10 or 20 μM cadmium chloride (CdCl2) for 9-15 weeks induced a high proliferative potential, the epithelial-mesenchymal transition (EMT), stress fiber formation, high cell motility, and resistance to anti-tumor drugs...
March 16, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28302216/-association-of-indoor-air-pollution-single-nucleotide-polymorphism-of-hif-1%C3%AE-gene-with-susceptibility-to-lung-cancer-in-han-population-in-fujian-province
#10
Fei He, Qi Qi, Xu Li, Rendong Xiao, Qiuping Xu, Weimin Xiong, Zhiqiang Liu, Lin Cai
BACKGROUND: Hypoxia inducible factor-1α (HIF-1α) is associated with the progression and metastasis of lung cancer. There are, however, few studies on the relationship between the single nucleotide polymorphisms of HIF-1α and susceptibility to lung cancer. Therefore, we aimed to investigate the relationship between indoor air pollution, HIF-1α rs2057482, and the susceptibility to primary lung cancer of the Fujian Han population. METHODS: The present study is a hospital-based case-control study...
March 20, 2017: Zhongguo Fei Ai za Zhi, Chinese Journal of Lung Cancer
https://www.readbyqxmd.com/read/28295343/epithelial-membrane-protein-2-emp2-deficiency-alters-placental-angiogenesis-mimicking-features-of-human-placental-insufficiency
#11
Carmen J Williams, Alison Chu, Wendy N Jefferson, David Casero, Deepthi Sudhakar, Nevil Khurana, Claire P Hogue, Chinmayi Aryasomayajula, Priya Patel, Peggy Sullivan, Elizabeth Padilla-Banks, Shabnam Mohandessi, Carla Janzen, Madhuri Wadehra
Epithelial membrane protein-2 (EMP2) is a tetraspan protein predicted to regulate placental development. Highly expressed in secretory endometrium and trophectoderm cells, previous studies suggest that it may regulate implantation by orchestrating the surface expression of integrins and other membrane proteins. In order to test the role of EMP2 in pregnancy, mice lacking EMP2 (Emp2(-/-) ) were generated. Emp2(-/-) females are fertile but have reduced litter sizes when carrying Emp2(-/-) but not Emp2(+/-) fetuses...
March 14, 2017: Journal of Pathology
https://www.readbyqxmd.com/read/28292897/inhibition-of-atherogenesis-by-the-cop9-signalosome-subunit-5-in-vivo
#12
Yaw Asare, Miriam Ommer, Florence A Azombo, Setareh Alampour-Rajabi, Marieke Sternkopf, Maryam Sanati, Marion J Gijbels, Corinna Schmitz, Dzmitry Sinitski, Pathricia V Tilstam, Hongqi Lue, André Gessner, Denise Lange, Johannes A Schmid, Christian Weber, Martin Dichgans, Joachim Jankowski, Ruggero Pardi, Menno P J de Winther, Heidi Noels, Jürgen Bernhagen
Constitutive photomorphogenesis 9 (COP9) signalosome 5 (CSN5), an isopeptidase that removes neural precursor cell-expressed, developmentally down-regulated 8 (NEDD8) moieties from cullins (thus termed "deNEDDylase") and a subunit of the cullin-RING E3 ligase-regulating COP9 signalosome complex, attenuates proinflammatory NF-κB signaling. We previously showed that CSN5 is up-regulated in human atherosclerotic arteries. Here, we investigated the role of CSN5 in atherogenesis in vivo by using mice with myeloid-specific Csn5 deletion...
March 14, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28286015/rutin-protects-against-h2o2-triggered-impaired-relaxation-of-placental-arterioles-and-induces-nrf2-mediated-adaptation-in-human-umbilical-vein-endothelial-cells-exposed-to-oxidative-stress
#13
Mireille M J P E Sthijns, Paul M Schiffers, Ger M Janssen, Kristien J A Lemmens, Bart Ides, Philippe Vangrieken, Freek G Bouwman, Edwin C Mariman, Irina Pader, Elias S J Arnér, Katarina Johansson, Aalt Bast, Guido R M M Haenen
BACKGROUND: Rutin intake is associated with a reduced risk of cardiovascular disease (CVD). The exact mechanism by which rutin can protect against CVD development is still enigmatic. Since, rutin is a compound with a relatively short half-life, the direct antioxidant effect of rutin cannot explain the long-lasting effect on human health. We hypothesized that rutin next to its direct antioxidant effect that improves endothelial function, may also induce an adaptive response in endogenous antioxidant systems...
March 7, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28285930/exploiting-the-cancer-niche-tumor-associated-macrophages-and-hypoxia-as-promising-synergistic-targets-for-nano-based-therapy
#14
REVIEW
Vera Silva, Wafa' T Al-Jamal
The tumor microenvironment has been widely exploited as an active participant in tumor progression. Extensive reports have defined the dual role of tumor-associated macrophages (TAMs) in tumor development. The protumoral effect exerted by the M2 phenotype has been correlated with a negative outcome in most solid tumors. The high infiltration of immune cells in the hypoxic cores of advanced solid tumors leads to a chain reaction of stimuli that enhances the expression of protumoral genes, thrives tumor malignancy, and leads to the emergence of drug resistance...
March 7, 2017: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/28285917/examining-the-structure-activity-relationship-of-benzopyran-based-inhibitors-of-the-hypoxia-inducible-factor-1-pathway
#15
Jalisa Ferguson, Zeus De Los Santos, Narra Devi, Erwin Van Meir, Sarah Zingales, Binghe Wang
Many forms of solid tumor have a characteristic feature known as hypoxia, which describes a low or non-existent presence of oxygen in the cellular microenvironment. This decrease in oxygen causes activation of the hypoxia inducible factor (HIF) pathway, which activates the transcription of many genes that cause cell proliferation, metastasis, increased glycolysis and angiogenesis. Increased HIF expression has been linked with poor patient prognosis, increased malignancy, and therapeutic resistance. Previous work in our lab has identified 1 and 2 as inhibitors of the HIF pathway, specifically as disrupters of the p300-HIF-1α complex formation...
March 1, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28279976/regulation-of-hypoxia-responses-by-flavin-adenine-dinucleotide-dependent-modulation-of-hif-1%C3%AE-protein-stability
#16
Suk-Jin Yang, Young Soo Park, Jung Hee Cho, Byul Moon, Hyun-Jung Ahn, Ju Yeon Lee, Zhi Xie, Yuli Wang, David Pocalyko, Dong Chul Lee, Hyun Ahm Sohn, Minho Kang, Jin Young Kim, Eunhee Kim, Kyung Chan Park, Jung-Ae Kim, Young Il Yeom
Oxygen deprivation induces a range of cellular adaptive responses that enable to drive cancer progression. Here, we report that lysine-specific demethylase 1 (LSD1) upregulates hypoxia responses by demethylating RACK1 protein, a component of hypoxia-inducible factor (HIF) ubiquitination machinery, and consequently suppressing the oxygen-independent degradation of HIF-1α. This ability of LSD1 is attenuated during prolonged hypoxia, with a decrease in the cellular level of flavin adenine dinucleotide (FAD), a metabolic cofactor of LSD1, causing HIF-1α downregulation in later stages of hypoxia...
March 9, 2017: EMBO Journal
https://www.readbyqxmd.com/read/28278175/pneumococcal-infection-of-respiratory-cells-exposed-to-welding-fumes-role-of-oxidative-stress-and-hif-1-alpha
#17
Jonathan Grigg, Lisa Miyashita, Reetika Suri
Welders are more susceptible to pneumococcal pneumonia. The mechanisms are yet unclear. Pneumococci co-opt the platelet activating factor receptor (PAFR) to infect respiratory epithelial cells. We previously reported that exposure of respiratory cells to welding fumes (WF), upregulates PAFR-dependent pneumococcal infection. The signaling pathway for this response is unknown, however, in intestinal cells, hypoxia-inducible factor-1 α (HIF 1α) is reported to mediate PAFR-dependent infection. We sought to assess whether oxidative stress plays a role in susceptibility to pneumococcal infection via the platelet activating factor receptor...
2017: PloS One
https://www.readbyqxmd.com/read/28273070/hypersensitive-termination-of-the-hypoxic-response-by-a-disordered-protein-switch
#18
Rebecca B Berlow, H Jane Dyson, Peter E Wright
The cellular response to hypoxia is critical for cell survival and is fine-tuned to allow cells to recover from hypoxic stress and adapt to heterogeneous or fluctuating oxygen levels. The hypoxic response is mediated by the α-subunit of the transcription factor HIF-1 (HIF-1α), which interacts through its intrinsically disordered C-terminal transactivation domain with the TAZ1 (also known as CH1) domain of the general transcriptional coactivators CBP and p300 to control the transcription of critical adaptive genes...
March 16, 2017: Nature
https://www.readbyqxmd.com/read/28271613/qiliqiangxin-protects-against-anoxic-injury-in-cardiac-microvascular-endothelial-cells-via-nrg-1-erbb-pi3k-akt-mtor-pathway
#19
Jingfeng Wang, Jingmin Zhou, Yanyan Wang, Chunjie Yang, Mingqiang Fu, Jingjing Zhang, Xueting Han, Zhiming Li, Kai Hu, Junbo Ge
Cardiac microvascular endothelial cells (CMECs) are important angiogenic components and are injured rapidly after cardiac ischaemia and anoxia. Cardioprotective effects of Qiliqiangxin (QL), a traditional Chinese medicine, have been displayed recently. This study aims to investigate whether QL could protect CMECs against anoxic injury and to explore related signalling mechanisms. CMECs were successfully cultured from Sprague-Dawley rats and exposed to anoxia for 12 hrs in the absence and presence of QL. Cell migration assay and capillary-like tube formation assay on Matrigel were performed, and cell apoptosis was determined by TUNEL assay and caspase-3 activity...
March 8, 2017: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/28267240/integrated-functions-of-membrane-type-1-matrix-metalloproteinase-in-regulating-cancer-malignancy-beyond-a-proteinase
#20
REVIEW
Takeharu Sakamoto, Motoharu Seiki
Membrane-type 1 matrix metalloproteinase (MT1-MMP) is expressed in different types of invasive and proliferative cells, including cancer cells and stromal cells. MT1-MMP cleaves extracellular matrix proteins, membrane proteins, and other pericellular proteins, thereby changing the cellular microenvironment and regulating signal activation. Critical roles of protease activity in cancer cell proliferation, invasion, and metastasis have been demonstrated by many groups. MT1-MMP also has a non-protease activity in that it inhibits the oxygen-dependent suppression of hypoxia-inducible factors (HIFs) via Munc18-1-interacting protein 3 (Mint3) and thereby enhances the expression of HIF target genes...
March 7, 2017: Cancer Science
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