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Hypoxia induced factor

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https://www.readbyqxmd.com/read/28445935/inhibition-of-mtorc2-component-rictor-impairs-tumor-growth-in-pancreatic-cancer-models
#1
Katharina M Schmidt, Claus Hellerbrand, Petra Ruemmele, Christoph W Michalski, Bo Kong, Alexander Kroemer, Christina Hackl, Hans J Schlitt, Edward K Geissler, Sven A Lang
Mammalian Target of Rapamycin complex 2 (mTORC2) and its regulatory component Rapamycin-insensitive companion of mTOR (RICTOR) are increasingly recognized as important players in human cancer development and progression. However, the role of RICTOR in human pancreatic ductal adenocarcinoma (PDAC) is unclear so far. Here, we sought to analyze the effects of RICTOR inhibition in human pancreatic cancer cell lines in vitro and in vivo. Furthermore, RICTOR expression was determined in human PDAC samples. Results demonstrate that depletion of RICTOR with siRNA (transient knock-down) or shRNA (stable knock-down) has an inhibitory effect on tumor growth in vitro...
April 11, 2017: Oncotarget
https://www.readbyqxmd.com/read/28445928/regulation-of-angiogenic-behaviors-by-oxytocin-receptor-through-gli1-indcued-transcription-of-hif-1%C3%AE-in-human-umbilical-vein-endothelial-cells
#2
Ji Zhu, Huiyan Wang, Xiaoyan Zhang, Yin Xie
Angiogenesis is a dynamic hypoxia-stimulated process playing a key role in tissue growth and repair under various pathophysiological circumstances. Abnormal angiogenesis contributes to the pathogenesis of many human diseases. Oxytocin receptor is a classical G-protein-coupled receptor expressed on endothelial cells. The present study was aimed to investigate how oxytocin receptor regulated the angiogenic behaviors of human umbilical vein endothelial cells (HUVECs). We found that oxytocin at 0.1μM significantly increased cell proliferation, upregulated the mRNA and protein expression of CD31 and vWF (two important endothelial markers), and enhanced the tuber formation capacity in HUVECs...
April 22, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28445205/inhibition-of-microrna-429-in-the-renal-medulla-increased-salt-sensitivity-of-blood-pressure-in-sprague-dawley-rats
#3
Qing Zhu, Junping Hu, Lei Wang, Weili Wang, Zhengchao Wang, Pin-Lan Li, Krishna M Boini, Ningjun Li
BACKGROUND: We have previously shown that high salt intake suppresses the expression of prolyl hydroxylase domain-containing protein 2 (PHD2), an enzyme promoting the degradation of hypoxia-inducible factor (HIF)-1α, and increases HIF-1α along with its target genes in the renal medulla, which promotes sodium excretion and regulate salt sensitivity of blood pressure. However, it remains unknown how high salt inhibits the expression of PHD2. METHOD AND RESULTS: The current study first revealed that high-salt-induced PHD2 inhibition was due to the enhanced decay of mRNA...
April 25, 2017: Journal of Hypertension
https://www.readbyqxmd.com/read/28445144/stroma-derived-hgf-drives-metabolic-adaptation-of-colorectal-cancer-to-angiogenesis-inhibitors
#4
Alessia Mira, Virginia Morello, Maria Virtudes Céspedes, Timothy Perera, Paolo M Comoglio, Ramon Mangues, Paolo Michieli
The role of paracrine Hepatocyte Growth Factor (HGF) in the resistance to angiogenesis inhibitors (AIs) is hidden in xenograft models because mouse HGF fails to fully activate human MET. To uncover it, we compared the efficacy of AIs in wild-type and human HGF knock-in SCID mice bearing orthotopic human colorectal tumors. Species-specific HGF/MET signaling dramatically impaired the response to anti-angiogenic agents and boosted metastatic dissemination. In cell-based assays mimicking the consequences of anti-angiogenic therapy, colorectal cancer cells were completely resistant to hypoxia but extremely sensitive to nutrient deprivation...
April 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28444966/correlation-between-genetic-polymorphisms-within-the-mapk1-hif-1-ho-1-signaling-pathway-and-risk-or-prognosis-of-perimenopausal-coronary-artery-disease
#5
Nan Guo, Nan Zhang, Liqiu Yan, Xufen Cao, Jiawang Wang, Yunfei Wang
BACKGROUND: Mitogen-activated protein kinase-1 (MAPK1), as well as its downstream factors of hypoxia-inducible factor-1 (HIF-1) and heme oxygenase-1 (HO-1), have been documented to be involved in modulating development of coronary artery disease (CAD). HYPOTHESIS: Genetic mutations within the MAPK1/HIF-1/HO-1 signaling pathway could alter the risk of perimenopausal CAD in Chinese patients. METHODS: Peripheral blood samples were gathered from 589 CAD patients and 860 healthy controls, and 12 potential single-nucleotide polymorphisms (SNPs) were obtained from HapMap database and previously published studies...
April 26, 2017: Clinical Cardiology
https://www.readbyqxmd.com/read/28443460/augmented-expression-of-runx1-deregulates-the-global-gene-expression-of-u87-glioblastoma-multiforme-cells-and-inhibits-tumor-growth-in-mice
#6
Yoel Bogoch, Gilgi Friedlander-Malik, Lior Lupu, Ekaterina Bondar, Nitzan Zohar, Sheila Langier, Zvi Ram, Ido Nachmany, Joseph M Klausner, Niv Pencovich
Glioblastoma multiforme is the most common and aggressive primary brain tumor in adults. A mesenchymal phenotype was associated with tumor aggressiveness and poor prognosis in glioblastoma multiforme patients. Recently, the transcription factor RUNX1 was suggested as a driver of the glioblastoma multiforme mesenchymal gene expression signature; however, its independent role in this process is yet to be described. Here, we assessed the role of RUNX1 in U87 glioblastoma multiforme cells in correspondence to its mediated transcriptome and genome-wide occupancy pattern...
April 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28443351/current-and-future-chemical-therapies-for-treating-anaemia-in-chronic-kidney-disease
#7
Francesco Locatelli, Lucia Del Vecchio, Maria Carmen Luise
Erythropoiesis-stimulating agents (ESAs) are not perfect, since they have potential side effects. Iron therapy is also receiving growing attention in recent years. Areas covered: We performed a literature search on PubMed using the following key words: anaemia, chronic kidney disease, HIF stabilisers, sotatercept, actin traps, iron, iron-containing phosphate binders, iron dialysate. We reviewed new drugs that are under clinical development to obtain better safety and activity and/or easier and cheaper manufacturing processes in comparison to available ESAs...
April 26, 2017: Expert Opinion on Pharmacotherapy
https://www.readbyqxmd.com/read/28443030/mitochondrial-reactive-oxygen-species-and-kidney-hypoxia-in-the-development-of-diabetic-nephropathy
#8
REVIEW
Tomas A Schiffer, Malou Friederich-Persson
The underlying mechanisms in the development of diabetic nephropathy are currently unclear and likely consist of a series of dynamic events from the early to late stages of the disease. Diabetic nephropathy is currently without curative treatments and it is acknowledged that even the earliest clinical manifestation of nephropathy is preceded by an established morphological renal injury that is in turn preceded by functional and metabolic alterations. An early manifestation of the diabetic kidney is the development of kidney hypoxia that has been acknowledged as a common pathway to nephropathy...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/28442737/structural-and-biochemical-insights-of-cypa-and-aif-interaction
#9
Biancamaria Farina, Gianluigi Di Sorbo, Angela Chambery, Andrea Caporale, Guido Leoni, Rosita Russo, Fabiola Mascanzoni, Domenico Raimondo, Roberto Fattorusso, Menotti Ruvo, Nunzianna Doti
The Cyclophilin A (CypA)/Apoptosis Inducing Factor (AIF) complex is implicated in the DNA degradation in response to various cellular stress conditions, such as oxidative stress, cerebral hypoxia-ischemia and traumatic brain injury. The pro-apoptotic form of AIF (AIF(Δ1-121)) mainly interacts with CypA through the amino acid region 370-394. The AIF(370-394) synthetic peptide inhibits complex formation in vitro by binding to CypA and exerts neuroprotection in a model of glutamate-mediated oxidative stress. Here, the binding site of AIF(Δ1-121) and AIF(370-394) on CypA has been mapped by NMR spectroscopy and biochemical studies, and a molecular model of the complex has been proposed...
April 25, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28442712/cardioprotective-effects-of-cu-ii-atsm-in-human-vascular-smooth-muscle-cells-and-cardiomyocytes-mediated-by-nrf2-and-dj-1
#10
Salil Srivastava, Philip J Blower, Aisah A Aubdool, Robert C Hider, Giovanni E Mann, Richard C Siow
Cu((II))ATSM was developed as a hypoxia sensitive positron emission tomography agent. Recent reports have highlighted the neuroprotective properties of Cu((II))ATSM, yet there are no reports that it confers cardioprotection. We demonstrate that Cu((II))ATSM activates the redox-sensitive transcription factor Nrf2 in human coronary artery smooth muscle cells (HCASMC) and cardiac myocytes (HCM), leading to upregulation of antioxidant defense enzymes. Oral delivery of Cu((II))ATSM in mice induced expression of the Nrf2-regulated enzymes in the heart and aorta...
December 21, 2016: Scientific Reports
https://www.readbyqxmd.com/read/28442264/mitochondrial-lon-protease-dependent-degradation-of-cytochrome-c-oxidase-subunits-under-hypoxia-and-myocardial-ischemia
#11
Naresh B V Sepuri, Rajesh Angireddy, Satish Srinivasan, Manti Guha, Joseph Spear, Bin Lu, Hindupur K Anandatheerthavarada, Carolyn K Suzuki, Narayan G Avadhani
The mitochondrial ATP dependent matrix protease, Lon, is involved in the maintenance of mitochondrial DNA nucleoids and degradation of abnormal or misfolded proteins. The Lon protease regulates mitochondrial Tfam (mitochondrial transcription factor A) level and thus modulates mitochondrial DNA (mtDNA) content. We have previously shown that hypoxic stress induces the PKA-dependent phosphorylation of cytochrome c oxidase (CcO) subunits I, IVi1, and Vb and a time-dependent reduction of these subunits in RAW 264...
April 22, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28440490/microrna-15a-inhibition-protects-against-hypoxia-reoxygenation-induced-apoptosis-of-cardiomyocytes-by-targeting-mothers-against-decapentaplegic-homolog-7
#12
Yang Yang, Shiao Ding, Gaojun Xu, Fei Chen, Fangbao Ding
Myocardial ischemia/reperfusion (I/R) injury is a major pathological process in coronary heart disease and cardiac surgery, and is associated with aberrant microRNA (miR) expression. Previous studies have demonstrated that inhibition of miR-15a expression may ameliorate I/R‑induced myocardial injury. In the present study, the potential role and underlying mechanism of miR‑15a in hypoxia/reoxygenation‑induced apoptosis of cardiomyocytes was investigated. Myocardial I/R was simulated in cultured H9c2 cells by 24 h hypoxia followed by 24 h reoxygenation...
April 12, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28440459/hypoxia-induced-mir-210-promoter-demethylation-enhances-proliferation-autophagy-and-angiogenesis-of-schwannoma-cells
#13
Zhengguang Wang, Mingsi Deng, Zhendong Liu, Song Wu
Hypoxia, a dominant feature in cancer occurrence and evolution, exists throughout the progression of most malignant tumors. This study focused on the mechanism of hypoxia-induced miR-210 upregulation, and the miR-210 functions in schwannoma. We detected microvascular density, vascular endothelial growth factor (VEGF) and miR-210 expression levels using schwannoma tissue mciroarray. The results showed that miR-210 expression was significantly associated with VEGF. Moreover, the cytological tests showed that hypoxia induced miR-210 expression, while reduce ephrin-A3 expression...
May 2017: Oncology Reports
https://www.readbyqxmd.com/read/28440427/downregulation-of-mir-200c-protects-cardiomyocytes-from-hypoxia-induced-apoptosis-by-targeting-gata-4
#14
Zhigang Chen, Shaoli Zhang, Changlei Guo, Jianhua Li, Wenfeng Sang
Hypoxia-induced cardiomyocyte apoptosis plays an important role in the development of ischemic heart disease. MicroRNAs (miRNAs or miRs) are emerging as critical regulators of hypoxia-induced cardiomyocyte apoptosis. miR-200c is an miRNA that has been reported to be related to apoptosis in various pathological processes; however, its role in hypoxia‑induced cardiomyocyte apoptosis remains unclear. In the present study, we aimed to investigate the potential role and underlying mechanism of miR-200c in regulating hypoxia‑induced cardiomyocyte apoptosis...
April 20, 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/28439929/the-roles-of-autophagy-and-hypoxia-in-human-inflammatory-periapical-lesions
#15
H Y Huang, W C Wang, P Y Lin, C P Huang, C Y Chen, Y K Chen
AIM: To determine the expressions of hypoxia-related [hypoxia-inducible transcription factors (HIF)-1α, BCL2/adenovirus E1B 19 kDa protein-interacting protein 3 (BNIP3), and phospho-adenosine monophosphate activated protein kinase (pAMPK)] and autophagy-related [microtubule-associated protein 1 light chain 3 (LC3), beclin-1 (BECN-1), autophagy-related gene (Atg)5-12, and p62] proteins in human inflammatory periapical lesions. METHODOLOGY: Fifteen samples of radicular cysts (RCs) and 21 periapical granulomas (PGs), combined with 17 healthy dental pulp tissues were examined...
April 25, 2017: International Endodontic Journal
https://www.readbyqxmd.com/read/28438094/association-of-atf4-expression-with-tissue-hypoxia-and-m2-macrophage-infiltration-in-infantile-hemangioma
#16
Hou-Fu Xia, Jun-Yi Zhu, Jing-Nan Wang, Jian-Gang Ren, Yu Cai, Feng-Qin Wang, Wei Zhang, Gang Chen, Yi-Fang Zhao, Ji-Hong Zhao
Accumulating studies have revealed the hypoxic condition and its crucial role in the distinctive progression of infantile hemangioma (IH), the most common benign tumor in infancy. Activating transcription factor 4 (ATF4), an important gene mediating cellular adaptation to various stress signals, could confer a survival advantage for tumor cells under hypoxia and regulate tumor progression. However, the potential role of ATF4 in IH was still unknown. In this study, the expression of hypoxia inducible factor (HIF)-1α, ATF4, and macrophage colony-stimulating factor (M-CSF) in 27 specimens of IH was measured by immunochemistry and double-labeling immunofluorescence, followed by the Spearman rank correlation test...
May 2017: Journal of Histochemistry and Cytochemistry: Official Journal of the Histochemistry Society
https://www.readbyqxmd.com/read/28437377/microrna-21-is-required-for-local-and-remote-ischemic-preconditioning-in-multiple-organ-protection-against-sepsis
#17
Ping Jia, Xiaoli Wu, Yan Dai, Jie Teng, Yi Fang, Jiachang Hu, Jianzhou Zou, Mingyu Liang, Xiaoqiang Ding
OBJECTIVE: Sepsis, triggered by microbial infection, is a common and life-threatening systemic illness, often leads to impaired function of vital organs. Ischemic preconditioning induced by transient brief episodes of ischemia is a powerful innate mechanism of organ protection. We have reported that a 15-minute renal ischemic preconditioning substantially attenuated subsequent renal ischemia-reperfusion injury. Here, we investigate whether a brief ischemia and reperfusion in kidney can provide protection at local and remote sites against sepsis-induced organ injury, and whether this protection is microRNA-21 dependent...
April 21, 2017: Critical Care Medicine
https://www.readbyqxmd.com/read/28437280/inhibition-of-rho-kinase-attenuates-left-ventricular-remodeling-caused-by-chronic-intermittent-hypoxia-in-rats-via-suppressing-myocardial-inflammation-and-apoptosis
#18
Zhi-Hua Wang, Die Zhu, Sheng Xie, Yan Deng, Yueying Pan, Jie Ren, Hui-Guo Liu
Chronic intermittent hypoxia (CIH), the hallmark of obstructive sleep apnea syndrome (OSAS), has been reported to play a key role in the development of OSAS-associated cardiovascular diseases including cardiac remodeling. RhoA/Rho-kinase (ROCK) pathway has also been implicated in myocardial remodeling, but the exact mechanisms are not fully elucidated. The current study's purpose is to investigate the influence of fasudil, a selective ROCK inhibitor, on CIH-induced left ventricular remodeling in rats and its possible mechanisms...
April 18, 2017: Journal of Cardiovascular Pharmacology
https://www.readbyqxmd.com/read/28436951/hypoxic-lung-cancer-secreted-exosomal-mir-23a-increased-angiogenesis-and-vascular-permeability-by-targeting-prolyl-hydroxylase-and-tight-junction-protein-zo-1
#19
Y-L Hsu, J-Y Hung, W-A Chang, Y-S Lin, Y-C Pan, P-H Tsai, C-Y Wu, P-L Kuo
Hypoxia plays a critical role during the evolution of malignant cells and tumour microenvironment (TME).Tumour-derived exosomes contain informative microRNAs involved in the interaction of cancer and stromal cells, thus contributing to tissue remodelling of tumour microenvironment. This study aims to clarify how hypoxia affects tumour angiogenesis through exosomes shed from lung cancer cells. Lung cancer cells produce more exosomes under hypoxic conditions than do parental cells under normoxic conditions. miR-23a was significantly upregulated in exosomes from lung cancer under hypoxic conditions...
April 24, 2017: Oncogene
https://www.readbyqxmd.com/read/28436940/disruption-of-spatiotemporal-hypoxic-signaling-causes-congenital-heart-disease-in-mice
#20
Xuejun Yuan, Hui Qi, Xiang Li, Fan Wu, Jian Fang, Eva Bober, Gergana Dobreva, Yonggang Zhou, Thomas Braun
Congenital heart disease (CHD) represents the most prevalent inborn anomaly. Only a minority of CHD cases are attributed to genetic causes, suggesting a major role of environmental factors. Nonphysiological hypoxia during early pregnancy induces CHD, but the underlying reasons are unknown. Here, we have demonstrated that cells in the mouse heart tube are hypoxic, while cardiac progenitor cells (CPCs) expressing islet 1 (ISL1) in the secondary heart field (SHF) are normoxic. In ISL1+ CPCs, induction of hypoxic responses caused CHD by repressing Isl1 and activating NK2 homeobox 5 (Nkx2...
April 24, 2017: Journal of Clinical Investigation
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