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https://www.readbyqxmd.com/read/27913198/argininosuccinate-synthetase-1-ass1-is-a-common-metabolic-marker-of-chemosensitivity-for-targeted-arginine-and-glutamine-starvation-therapy
#1
Yan Long, Wen-Bin Tsai, Dajuan Wang, David H Hawke, Niramol Savaraj, Lynn G Feun, Mien-Chie Hung, Helen H W Chen, Macus Tien Kuo
Argininosuccinate synthetase 1 (ASS1) is the rate-limiting enzyme that catalyzes the biosynthesis of arginine (Arg). Many malignant human tumors are auxotrophic for Arg because ASS1 is silenced. ASS1 has been established as a sensor of Arg auxotrophic response and a chemosensitivity marker for Arg starvation therapy. Here, we report that ASS1 is also a sensor for glutamine (Gln)-deprivation response, and that upregulation of ASS1 expression is associated with resistance to Gln-starvation treatments. Knockdown of ASS1 expression resulted in increased sensitivity to both Arg- and Gln-starvation, whereas increased ASS1 expression by ectopic transfection is associated with resistance to both Arg- and Gln-starvation...
November 29, 2016: Cancer Letters
https://www.readbyqxmd.com/read/27909249/mortalin-mediated-and-erk-controlled-targeting-of-hif-1%C3%AE-to-mitochondria-confers-resistance-to-apoptosis-under-hypoxia
#2
Ilias Mylonis, Maria Kourti, Martina Samiotaki, George Panayotou, George Simos
Hypoxia inducible factor-1 (HIF-1) is the main transcriptional activator of the cellular response to hypoxia and an important target of anticancer therapy. Phosphorylation by ERK stimulates the transcriptional activity of HIF-1α by inhibiting its CRM1-dependent nuclear export. Here, we demonstrate that phosphorylation by ERK also regulates the association of HIF-1α with a novel interaction partner identified as mortalin (GRP75) which mediates non-genomic involvement of HIF-1α in apoptosis. Mortalin binds specifically to HIF-1α lacking modification by ERK and their complex is localized outside the nucleus...
December 1, 2016: Journal of Cell Science
https://www.readbyqxmd.com/read/27903985/the-tissue-inhibitor-of-metalloproteinases-1-timp-1-promotes-survival-and-migration-of-acute-myeloid-leukemia-cells-through-cd63-pi3k-akt-p21-signaling
#3
Dorian Forte, Valentina Salvestrini, Giulia Corradi, Lara Rossi, Lucia Catani, Roberto M Lemoli, Michele Cavo, Antonio Curti
We and others have shown that the Tissue Inhibitor of Metalloproteinases-1 (TIMP-1), a member of the inflammatory network exerting pleiotropic effects in the bone marrow (BM) microenvironment, regulates the survival and proliferation of different cell types, including normal hematopoietic progenitor cells. Moreover, TIMP-1 has been shown to be involved in cancer progression. However, its role in leukemic microenvironment has not been addressed. Here, we investigated the activity of TIMP-1 on Acute Myelogenous Leukemia (AML) cell functions...
November 26, 2016: Oncotarget
https://www.readbyqxmd.com/read/27903434/hypoxia-and-hif-1-activation-in-bacterial-infections
#4
Gayatri Devraj, Christiane Beerlage, Bernhard Brüne, Volkhard A J Kempf
For most of the living being, oxygen is one of the essential elements required to sustain life. Deprivation of oxygen causes tissue hypoxia and this affects host cell and organ functions severely. Tissue hypoxia is a prominent microenvironmental condition occurring in infections and there is a body of evidence that hypoxia and inflammation are interconnected with each other. The primary key factor mediating the mammalian hypoxic response is hypoxia inducible factor (HIF)-1, which regulates oxygen homeostasis on cellular, tissue and organism levels...
November 26, 2016: Microbes and Infection
https://www.readbyqxmd.com/read/27902314/newcastle-disease-virus-degrades-hif-1%C3%AE-through-proteasomal-pathways-independent-of-vhl-and-p53
#5
Noraini Abd-Aziz, Eric Stanbridge, Norazizah Shafee
Newcastle disease virus (NDV) is a candidate agent for oncolytic virotherapy. Despite its potential, the exact mechanism of its oncolysis is still not known. Recently, we reported that NDV exhibited an increased oncolytic activity in hypoxic cancer cells. These types of cells negatively affect therapeutic outcome by overexpressing pro-survival genes under the control of the hypoxia-inducible factor (HIF). HIF-1 is a heterodimeric transcriptional factor consisting of a regulated alpha (HIF-1α) and a constitutive beta subunit (HIF-1β)...
October 6, 2016: Journal of General Virology
https://www.readbyqxmd.com/read/27901482/hyperglycemia-triggers-hipk2-protein-degradation
#6
Silvia Baldari, Alessia Garufi, Marisa Granato, Laura Cuomo, Giuseppa Pistritto, Mara Cirone, Gabriella D'Orazi
Homeodomain interacting protein kinase-2 (HIPK2) is an evolutionary conserved kinase that modulates several key molecular pathways to restrain tumor growth and induce p53-depending apoptotic cell-death in response to anticancer therapies. HIPK2 silencing in cancer cells leads to chemoresistance and cancer progression, in part due to p53 inhibition. Recently, hyperglycemia has been shown to reduce p53 phosphorylation at serine 46 (Ser46), the target residue of HIPK2, thus impairing p53 apoptotic function. Here we asked whether hyperglycemia could, upstream of p53, target HIPK2...
November 25, 2016: Oncotarget
https://www.readbyqxmd.com/read/27900001/expression-of-glucose-transporter-1-is-correlated-with-hypoxia-inducible-factor-1%C3%AE-and-malignant-potential-in-pancreatic-neuroendocrine-tumors
#7
Minoru Fujino, Shinichi Aishima, Koji Shindo, Yasunori Oda, Katsuya Morimatsu, Kosuke Tsutsumi, Takao Otsuka, Masao Tanaka, Yoshinao Oda
The present study aimed to investigate the prognostic usefulness of the expression of glucose transporter type 1 (GLUT-1) and GLUT-2, hypoxia-inducible factor 1α (HIF-1α) and insulin-like growth factor II messenger RNA-binding protein 3 (IMP3) in pancreatic neuroendocrine tumors (pNETs). Immunohistochemical staining for GLUT-1, GLUT-2, HIF-1α and IMP3 was performed in 70 pNET specimens. The expression of GLUT-1 and HIF-1α was significantly higher in the World Health Organization grade 2 (G2), neuroendocrine carcinoma cases and mixed-type pNETs compared with the G1 cases...
November 2016: Oncology Letters
https://www.readbyqxmd.com/read/27899277/protective-role-of-hypoxia-inducible-factor-1%C3%AE-dependent-cd39-and-cd73-in-fulminant-acute-liver-failure
#8
Eunyoung Tak, Dong-Hwan Jung, Seok-Hwan Kim, Gil-Chun Park, Dae Young Jun, Jooyoung Lee, Bo-Hyun Jung, Varvara A Kirchner, Shin Hwang, Gi-Won Song, Sung-Gyu Lee
Acute liver failure (ALF) is a severe life-threatening disease which usually arises in patients with-irreversible liver illnesses. Although human ectonucleotide triphosphate diphosphohydrolase-1, E-NTPDase1 (CD39) and ecto-5'-nucleotidase, Ecto5'NTase (CD73) are known to protect tissues from ALF, the expression and function of CD39 and CD73 during ALF are currently not fully investigated. We tested whether CD39 and CD73 are upregulated by hypoxia inducible factor (HIF)-1α, and improve ischemic tolerance to ALF...
November 27, 2016: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/27896629/remote-limb-ischemic-preconditioning-protects-rats-against-cerebral-ischemia-via-hif-1%C3%AE-ampk-hsp70-pathway
#9
Ming Xia, Qian Ding, Zhidan Zhang, Qinggen Feng
Remote limb ischemic preconditioning (RIPC) is a clinically feasible strategy to protect against ischemia/reperfusion injury, but the knowledge concerning the mechanism underlying RIPC is scarce. This study was performed to examine the effect of RIPC on brain tissue suffering from ischemia challenge and explore its underlying mechanism in a rat model. The animals were divided into four groups: Sham, middle cerebral artery occlusion (MCAO), RIPC, and MCAO+RIPC. We found that previous exposure to RIPC significantly attenuated neurological dysfunction and lessened brain edema in MCAO+RIPC group...
November 28, 2016: Cellular and Molecular Neurobiology
https://www.readbyqxmd.com/read/27883071/mint3-apba3-depletion-ameliorates-severe-murine-influenza-pneumonia-and-macrophage-cytokine-production-in-response-to-the-influenza-virus
#10
Takayuki Uematsu, Tomoko Fujita, Hiroki J Nakaoka, Toshiro Hara, Noritada Kobayashi, Yoshinori Murakami, Motoharu Seiki, Takeharu Sakamoto
Influenza virus (IFV) infection is a common cause of severe pneumonia. Studies have suggested that excessive activation of the host immune system including macrophages is responsible for the severe pathologies mediated by IFV infection. Here, we focused on the X11 protein family member Mint3/Apba3, known to promote ATP production via glycolysis by activating hypoxia inducible factor-1 (HIF-1) in macrophages, and examined its roles in lung pathogenesis and anti-viral defence upon IFV infection. Mint3-deficient mice exhibited improved influenza pneumonia with reduced inflammatory cytokines/chemokine levels and neutrophil infiltration in the IFV-infected lungs without alteration in viral burden, type-I interferon production, or acquired immunity...
November 24, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27877208/selection-analysis-and-improvement-of-anti-angiogenesis-compounds-identified-by-an-anti-hif-1%C3%AE-screening-and-validation-system
#11
Chikezie Madu, Liyuan Li, Yi Lu
Cancer cells resort to activating hypoxia-inducible factor-1 (HIF-1) as one of several responses to hypoxic conditions. Overexpression of HIF-1, the transcriptional regulator for a group of malignant-pathway related genes including vascular endothelial growth factor (VEGF), is associated with increased tumor growth, vascularization, and metastasis. HIF-1 is composed of an inducible subunit, HIF-1α and a constitutively expressed subunit, HIF-1ß. HIF-1 activity is mainly dependent on the level of HIF-1α protein, the inducible and regulatory subunit of the HIF-1 heterodimer complex; thus, identification of novel anti-HIF-1α agents will lead to effective blockage of the HIF-1 (HIF-1α)-mediated "switch-on" function for those malignant-pathway related genes and suppression of the HIF-1α/VEGF-mediated signaling pathway that promotes cancer progression and metastasis...
2016: Journal of Cancer
https://www.readbyqxmd.com/read/27877088/aloe-emodin-suppresses-hypoxia-induced-retinal-angiogenesis-via-inhibition-of-hif-1%C3%AE-vegf-pathway
#12
Jianming Wu, Xiao Ke, Wei Wang, Hongcheng Zhang, Na Ma, Wei Fu, Manxi Zhao, Xiaoping Gao, Xiaofeng Hao, Zhirong Zhang
Background: Aloe-emodin (AE) has been reported to possess the antiangiogenic effect on laser induced choroidal neovascularization. AE inhibits the vessel formation in the zebrafish embryos. However, it is still unclear whether AE can alleviate neovascularization. Here, we investigated the inhibitory effect of AE on the hypoxia-induced retinal neovascularization and the possible mechanisms. Methods: We established a vascular endothelial growth factor (VEGF) secretion model under chemical induced hypoxia by exposure of 150 µM CoCl2 to the ARPE-19 cells, then treated the cells with different concentrations of AE (0...
2016: International Journal of Biological Sciences
https://www.readbyqxmd.com/read/27862498/all-trans-retinoic-acid-preconditioning-enhances-proliferation-angiogenesis-and-migration-of-mesenchymal-stem-cell-in-vitro-and-enhances-wound-repair-in-vivo
#13
M Pourjafar, M Saidijam, K Mansouri, H Ghasemibasir, F Karimi Dermani, R Najafi
OBJECTIVES: Stem cell therapy is considered to be a suitable alternative in treatment of a number of diseases. However, there are challenges in their clinical application in cell therapy, such as to reduce survival and loss of transplanted stem cells. It seems that chemical and pharmacological preconditioning enhances their therapeutic efficacy. In this study, we investigated effects of all-trans retinoic acid (ATRA) on survival, angiogenesis and migration of mesenchymal stem cells (MSCs) in vitro and in a wound-healing model...
November 10, 2016: Cell Proliferation
https://www.readbyqxmd.com/read/27861614/photobiomodulation-with-pulsed-and-continuous-wave-near-infrared-laser-810-nm-al-ga-as-augments-dermal-wound-healing-in-immunosuppressed-rats
#14
Gaurav K Keshri, Asheesh Gupta, Anju Yadav, Sanjeev K Sharma, Shashi Bala Singh
Chronic non-healing cutaneous wounds are often vulnerable in one or more repair phases that prevent normal healing and pose challenges to the use of conventional wound care modalities. In immunosuppressed subject, the sequential stages of healing get hampered, which may be the consequences of dysregulated or stagnant wound inflammation. Photobiomodulation (PBM) or low-level laser (light) therapy (LLLT) emerges as a promising drug-free, non-invasive biophysical approach for promoting wound healing, reduction of inflammation, pain and restoration of functions...
2016: PloS One
https://www.readbyqxmd.com/read/27861592/hyperoxia-induced-proliferative-retinopathy-early-interruption-of-retinal-vascular-development-with-severe-and-irreversible-neurovascular-disruption
#15
Michelle Lajko, Herminio J Cardona, Joann M Taylor, Ronil S Shah, Kathryn N Farrow, Amani A Fawzi
Bronchopulmonary dysplasia (BPD) is a major cause of neonatal morbidity in premature infants, occurring as a result of arrested lung development combined with multiple postnatal insults. Infants with BPD exposed to supplemental oxygen are at risk of retinopathy of prematurity as well. Thus, we studied the effects of hyperoxia on the retinal vasculature in a murine model of BPD. The retinal phenotype of this model, which we termed hyperoxia-induced proliferative retinopathy (HIPR), shows severe disruption of retinal vasculature and loss of vascular patterning, disorganized intra-retinal angiogenesis, inflammation and retinal detachment...
2016: PloS One
https://www.readbyqxmd.com/read/27860185/sildenafil-attenuates-hypoxic-pulmonary-remodelling-by-inhibiting-bone-marrow-progenitor-cells
#16
Shirley Favre, Elisa Gambini, Patrizia Nigro, Alessandro Scopece, Paola Bianciardi, Anna Caretti, Giulio Pompilio, Antonio F Corno, Giuseppe Vassalli, Ludwig K von Segesser, Michele Samaja, Giuseppina Milano
The recruitment of bone marrow (BM)-derived progenitor cells to the lung is related to pulmonary remodelling and the pathogenesis of pulmonary hypertension (PH). Although sildenafil is a known target in PH treatment, the underlying molecular mechanism is still elusive. To test the hypothesis that the therapeutic effect of sildenafil is linked to the reduced recruitment of BM-derived progenitor cells, we induced pulmonary remodelling in rats by two-week exposure to chronic hypoxia (CH, 10% oxygen), a trigger of BM-derived progenitor cells...
November 18, 2016: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/27858285/the-role-of-hypoxia-inducible-factor-1-in-mild-cognitive-impairment
#17
REVIEW
Osigbemhe Iyalomhe, Sabina Swierczek, Ngozi Enwerem, Yuanxiu Chen, Monica O Adedeji, Joanne Allard, Oyonumo Ntekim, Sheree Johnson, Kakra Hughes, Philip Kurian, Thomas O Obisesan
Neuroinflammation and reactive oxygen species are thought to mediate the pathogenesis of Alzheimer's disease (AD), suggesting that mild cognitive impairment (MCI), a prodromal stage of AD, may be driven by similar insults. Several studies document that hypoxia-inducible factor 1 (HIF-1) is neuroprotective in the setting of neuronal insults, since this transcription factor drives the expression of critical genes that diminish neuronal cell death. HIF-1 facilitates glycolysis and glucose metabolism, thus helping to generate reductive equivalents of NADH/NADPH that counter oxidative stress...
November 17, 2016: Cellular and Molecular Neurobiology
https://www.readbyqxmd.com/read/27858190/nitro-oleic-acid-prevents-hypoxia-and-asymmetric-dimethylarginine-induced-pulmonary-endothelial-dysfunction
#18
Adolf Koudelka, Gabriela Ambrozova, Anna Klinke, Tana Fidlerova, Hana Martiskova, Radek Kuchta, Tanja K Rudolph, Jaroslav Kadlec, Zdenka Kuchtova, Steven R Woodcock, Bruce A Freeman, Lukas Kubala, Michaela Pekarova
RATIONALE: Pulmonary hypertension (PH) represents a serious health complication accompanied with hypoxic conditions, elevated levels of asymmetric dimethylarginine (ADMA), and overall dysfunction of pulmonary vascular endothelium. Since the prevention strategies for treatment of PH remain largely unknown, our study aimed to explore the effect of nitro-oleic acid (OA-NO2), an exemplary nitro-fatty acid (NO2-FA), in human pulmonary artery endothelial cells (HPAEC) under the influence of hypoxia or ADMA...
November 17, 2016: Cardiovascular Drugs and Therapy
https://www.readbyqxmd.com/read/27856259/potential-suppression-of-the-high-glucose-and-insulin-induced-retinal-neovascularization-by-sirtuin-3-in-the-human-retinal-endothelial-cells
#19
Xin-Bang Mao, Zhi-Peng You, Chen Wu, Jun Huang
Retinal neovascularization generally play roles in the formation of various severe eye diseases, such as age-related macular degeneration and diabetic retinopathy. The regulation of neovascularization-related pathways by Sirtuin 3 (Sirt3), a major mitochondrial NAD(+)-dependent deacetylase, give us a cue that Sirt3 may participate in the retinal neovascularization. However, the mechanism remains unclear. Here, we established a retinal neovascularization model by using human retinal endothelial cells (HRECs) under the induction of high glucose and insulin (HGI)...
November 14, 2016: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27852386/-association-between-genetic-polymorphisms-of-hif-2%C3%AE-gene-and-high-altitude-pulmonary-hypertension-in-han-population
#20
Z K Yu, Y J Han, D D Chen, X F Zhang, R Chang
Objective: To test the hypothesis that the single nucleotide polymorphisms (SNPs) in HIF-2α gene were associated with the susceptibility of high altitude pulmonary hypertension (HAPH) in Han population in China. Methods: Those Han population who emigrated to plateau (average altitude 3 300 m) and have been lived here for more than 20 years were included as the research subjects, the method of cluster random sampling was used to enroll 49 HAPH patients as the case group (HAPH group) and 39 free of HAPH people as the control group...
November 1, 2016: Zhonghua Yi Xue za Zhi [Chinese medical journal]
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