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https://www.readbyqxmd.com/read/28320188/clinical-significance-of-changes-in-serum-neuroglobin-and-hif-1%C3%AE-concentrations-during-the-early-phase-of-acute-ischemic-stroke
#1
Lixia Xue, Hao Chen, Kaili Lu, Jiankang Huang, Hao Duan, Yuwu Zhao
BACKGROUND: Neuroglobin (NGB) has been described as a neuroprotective agent in cerebral ischemia, hypoxia inducible factor (HIF) has shown an important role in modulating hypoxic and ischemic injury, and therefore they have the potential to impact outcomes after acute ischemic stroke (AIS). Thus, we investigated early changes in the concentrations of serum NGB and HIF-1α after AIS and evaluated the relations of both NGB and HIF-1α to stroke severity and prognosis. METHODS: We prospectively measured the serum concentrations of NGB and HIF-1α in 40 patients with AIS at 24, 48, 72, and 96h after stroke...
April 15, 2017: Journal of the Neurological Sciences
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
#2
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
#3
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/28315493/an-osteogenesis-angiogenesis-stimulation-artificial-ligament-for-anterior-cruciate-ligament-reconstruction
#4
Hong Li, Jinyan Li, Jia Jiang, Fang Lv, Jiang Chang, Shiyi Chen, Chengtie Wu
To solve the poor healing of polyethylene terephthalate (PET) artificial ligament in bone tunnel, copper-containing bioactive glass (Cu-BG) nanocoatings on PET artificial ligaments were successfully prepared by pulsed laser deposition (PLD). It was hypothesized that Cu-BG coated PET (Cu-BG/PET) grafts could enhance the in vitro osteogenic and angiogenic differentiation of rat bone marrow mesenchymal stem cells (rBMSCs) and in vivo graft-bone healing after anterior cruciate ligament (ACL) reconstruction in a goat model...
March 14, 2017: Acta Biomaterialia
https://www.readbyqxmd.com/read/28315322/new-horizons-in-hypoxia-signaling-pathways
#5
Christopher W Pugh, Peter J Ratcliffe
Investigation into the regulation of the erythropoietin gene by oxygen led to the discovery of a process of direct oxygen sensing that transduces many cellular and systemic responses to hypoxia. The oxygen-sensitive signal is generated through the catalytic action of a series of 2-oxoglutarate-dependent oxygenases that regulate the transcription factor hypoxia-inducible factor (HIF) by the post-translational hydroxylation of specific amino acid residues. Here we review the implications of the unforeseen complexity of the HIF transcriptional cascade for the physiology and pathophysiology of hypoxia, and consider the origins of post-translational hydroxylation as a signaling process...
March 14, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/28314761/hypoxia-mediated-regulation-of-the-secretory-properties-of-mitral-valve-interstitial-cells
#6
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
#7
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/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
#8
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/28296633/the-vacuolar-atpase-complex-and-assembly-factors-tmem199-and-ccdc115-control-hif1%C3%AE-prolyl-hydroxylation-by-regulating-cellular-iron-levels
#9
Anna L Miles, Stephen P Burr, Guinevere L Grice, James A Nathan
Hypoxia Inducible transcription Factors (HIFs) are principally regulated by the 2-oxoglutarate and Iron(II) prolyl hydroxylase (PHD) enzymes, which hydroxylate the HIFα subunit, facilitating its proteasome-mediated degradation. Observations that HIFα hydroxylation can be impaired even when oxygen is sufficient emphasise the importance of understanding the complex nature of PHD regulation. Here, we use an unbiased genome-wide genetic screen in near-haploid human cells to uncover cellular processes that regulate HIF1α...
March 15, 2017: ELife
https://www.readbyqxmd.com/read/28295343/epithelial-membrane-protein-2-emp2-deficiency-alters-placental-angiogenesis-mimicking-features-of-human-placental-insufficiency
#10
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/28285917/examining-the-structure-activity-relationship-of-benzopyran-based-inhibitors-of-the-hypoxia-inducible-factor-1-pathway
#11
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/28274939/long-term-hif-1%C3%AE-transcriptional-activation-is-essential-for-heat-acclimation-mediated-cross-tolerance-mitochondrial-target-genes
#12
Rivka Alexander-Shani, Ahmad Mreisat, Elia Smeir, Gary Gerstenblith, Michael D Stern, Michal Horowitz
An important adaptive feature of heat acclimation (AC) is the induction of cross-tolerance against novel stressors (HACT). Reprogramming of gene expression leading to enhanced innate cytoprotective features by attenuating damage and/or enhancing the response of "help" signals, plays a pivotal role. HIF-1α, constitutively upregulated by AC (1mo, 34°C), is a crucial transcription factor in this program, although its specific role is as yet unknown. By using a rat AC model we studied the impact of disrupting HIF-1α transcriptional activation [(HIF-1α:HIF-1β dimerization blockade by Acriflavine (4mg/kg b...
March 8, 2017: American Journal of Physiology. Regulatory, Integrative and Comparative Physiology
https://www.readbyqxmd.com/read/28273642/idh-mutations-associated-impact-on-related-cancer-epidemiology-and-subsequent-effect-toward-hif-1%C3%AE
#13
REVIEW
Herve Semukunzi, Debmalya Roy, Hongyang Li, Ghulam Jilany Khan, Xiaodan Lyu, Shengtao Yuan, Sensen Lin
Particular mutations in the isocitrate dehydrogenase gene (IDH) were discovered in several gliomas citing astrocytoma, oligodendroglioma, and glioblastoma multiform, but also in leukemia; these mutations were discovered in nearly all cases of secondary glioblastomas, they evolve from lower-grade gliomas, but are limited in primary high-grade glioblastoma multiform. These mutations distinctively produce (D)-2-hydroxyglutarate (D-2-HG) from alpha-ketoglutarate (α-KG). (D)-2-hydroxyglutarate is accumulated to very high concentrations which inhibit the function of enzymes that are dependent on alpha-ketoglutarate...
March 5, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28271615/neurotropin%C3%A2-alleviates-hippocampal-neuron-damage-through-a-hif-1%C3%AE-mapk-pathway
#14
Wen-Li Fang, De-Qiang Zhao, Fei Wang, Mei Li, Sheng-Nuo Fan, Wang Liao, Yu-Qiu Zheng, Shao-Wei Liao, Song-Hua Xiao, Ping Luan, Jun Liu
AIMS: The main purpose was to verify the potent capacity of Neurotropin® against neuronal damage in hippocampus and to explore its underlying mechanisms. METHODS: HT22 cells were treated with 40 μmol/L Aβ25-35 in the presence of various concentrations of Neurotropin® or in its absence. The cell viability was assessed with a CCK-8 assay, and flow cytometry was used to measure cell apoptosis, intracellular ROS levels, and mitochondrial membrane potential. Aβ plaques were examined by Bielschowsky silver staining, and the activities of antioxidants were detected in hippocampus of APP/PS1 mice after Neurotropin® treatment...
March 7, 2017: CNS Neuroscience & Therapeutics
https://www.readbyqxmd.com/read/28270773/renal-hypoxia-in-ckd-pathophysiology-and-detecting-methods
#15
REVIEW
Yosuke Hirakawa, Tetsuhiro Tanaka, Masaomi Nangaku
Chronic kidney disease (CKD) is a major public health problem. Accumulating evidence suggests that CKD aggravates renal hypoxia, and in turn, renal hypoxia accelerates CKD progression. To eliminate this vicious cycle, hypoxia-related therapies, such as hypoxia-inducible factor (HIF) activation (prolyl hydroxylase domain inhibition) or NF-E2-related factor 2 activation, are currently under investigation. Clinical studies have revealed heterogeneity in renal oxygenation; therefore, the detection of patients with more hypoxic kidneys can be used to identify likely responders to hypoxia-oriented therapies...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/28268243/immunomodulatory-glc-man-directed-dolichos-lablab-lectin-dll-evokes-anti-tumor-response-in-vivo-by-counteracting-angiogenic-gene-expressions
#16
V Vigneshwaran, Prabhu Thirusangu, Vijay Avin Br, V Krishna, Siddanakoppalu N Pramod, B T Prabhakar
Neovascularization and jeopardized immunity has been critically emphasized for the establishment of malignant progression. Lectins are the diverse class of carbohydrate interacting proteins having great potential as immunopotentiating and anticancer agents. The present investigation sought to demonstrate the antiproliferative activity of Dolichos lablab lectin (DLL) encompassing immunomodulatory attribute. DLL specific to glucose and mannose carbohydrate moieties has been purified to homogeneity from the common dietary legume Dolichos lablab...
March 7, 2017: Clinical and Experimental Immunology
https://www.readbyqxmd.com/read/28266128/ablation-of-endothelial-prolyl-hydroxylase-domain-protein-2-promotes-renal-vascular-remodelling-and-fibrosis-in-mice
#17
Shuo Wang, Heng Zeng, Sean T Chen, Liying Zhou, Xue-Jiao Xie, Xiaochen He, Yong-Kang Tao, Qin-Hui Tuo, Changqin Deng, Duan-Fang Liao, Jian-Xiong Chen
Accumulating evidence demonstrates that hypoxia-inducible factor (HIF-α) hydroxylase system has a critical role in vascular remodelling. Using an endothelial-specific prolyl hydroxylase domain protein-2 (PHD2) knockout (PHD2(EC) KO) mouse model, this study investigates the regulatory role of endothelial HIF-α hydroxylase system in the development of renal fibrosis. Knockout of PHD2 in EC up-regulated the expression of HIF-1α and HIF-2α, resulting in a significant decline of renal function as evidenced by elevated levels of serum creatinine...
March 7, 2017: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/28263965/l-2-hydroxyglutarate-production-arises-from-noncanonical-enzyme-function-at-acidic-ph
#18
Andrew M Intlekofer, Bo Wang, Hui Liu, Hardik Shah, Carlos Carmona-Fontaine, Ariën S Rustenburg, Salah Salah, M R Gunner, John D Chodera, Justin R Cross, Craig B Thompson
The metabolite 2-hydroxyglutarate (2HG) can be produced as either a D-R- or L-S- enantiomer, each of which inhibits α-ketoglutarate (αKG)-dependent enzymes involved in diverse biologic processes. Oncogenic mutations in isocitrate dehydrogenase (IDH) produce D-2HG, which causes a pathologic blockade in cell differentiation. On the other hand, oxygen limitation leads to accumulation of L-2HG, which can facilitate physiologic adaptation to hypoxic stress in both normal and malignant cells. Here we demonstrate that purified lactate dehydrogenase (LDH) and malate dehydrogenase (MDH) catalyze stereospecific production of L-2HG via 'promiscuous' reduction of the alternative substrate αKG...
March 6, 2017: Nature Chemical Biology
https://www.readbyqxmd.com/read/28263817/mir-34a-contributes-to-diabetes-related-cochlear-hair-cell-apoptosis-via-sirt1-hif-1%C3%AE-signaling
#19
Ying Lin, Jinjin Shen, Danfeng Li, Jie Ming, Xiangyang Liu, Nana Zhang, Jingbo Lai, Min Shi, Qiuhe Ji, Ying Xing
Type 2 diabetes (T2DM) has been considered to be associated with a higher likelihood of hearing impairment (HI). However, the molecular mechanisms underlying the association between diabetes and HI are poorly understood. MicroRNAs have recently been demonstrated to be closely associated with hearing loss and considered as promising therapeutic targets. Herein, we investigated whether miR-34a contributes to diabetes-related cochlear hair cell apoptosis and sought to identify the underlying mechanism. The results showed that miR-34a was up-regulated in the cochleas of db/db mice, accompanied by significant hearing threshold elevation and hair cell loss...
March 2, 2017: General and Comparative Endocrinology
https://www.readbyqxmd.com/read/28263291/iron-suppresses-erythropoietin-expression-via-oxidative-stress-dependent-hypoxia-inducible-factor-2-alpha-inactivation
#20
Keisuke Oshima, Yasumasa Ikeda, Yuya Horinouchi, Hiroaki Watanabe, Hirofumi Hamano, Yoshitaka Kihira, Seiji Kishi, Yuki Izawa-Ishizawa, Licht Miyamoto, Tasuku Hirayama, Hideko Nagasawa, Keisuke Ishizawa, Koichiro Tsuchiya, Toshiaki Tamaki
Renal anemia is a major complication in chronic kidney disease (CKD). Iron supplementation, as well as erythropoiesis-stimulating agents, are widely used for treatment of renal anemia. However, excess iron causes oxidative stress via the Fenton reaction, and iron supplementation might damage remnant renal function including erythropoietin (EPO) production in CKD. EPO gene expression was suppressed in mice following direct iron treatment. Hypoxia-inducible factor-2 alpha (HIF-2α), a positive regulator of the EPO gene, was also diminished in the kidney of mice following iron treatment...
March 6, 2017: Laboratory Investigation; a Journal of Technical Methods and Pathology
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