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https://www.readbyqxmd.com/read/28822855/tetrandrine-cardioprotection-in-ischemia-reperfusion-i-r-injury-via-jak3-stat3-hexokinase-ii
#1
Tie-Jun Zhang, Rui-Xia Guo, Xia Li, Yan-Wei Wang, Yong-Jun Li
Tetrandrine(TET), a bisbenzylisoquinoline alkaloid has been used for the treatment of cardiovascular diseases and hypertension. This study was to investigate whether tetrandrine exerts cardioprotection in ischemia-reperfusion (I/R) injury and the mechanisms involved. The cardioprotection effect and mechanisms of tetrandrine was evaluated by I/R injury cardiac cell model. Hexokinase II (HKII) is the critical regulators of mitochondrial dysfunction in cardiac I/R injury and it participate in the regulation of glycolysis and energy metabolism...
August 16, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28822229/vasculogenesis-and-angiogenesis-initiation-under-normoxic-conditions-through-wnt-%C3%AE-catenin-pathway-in-gliomas
#2
Alexandre Vallée, Rémy Guillevin, Jean-Noël Vallée
The canonical Wnt/β-catenin pathway is up-regulated in gliomas and involved in proliferation, invasion, apoptosis, vasculogenesis and angiogenesis. Nuclear β-catenin accumulation correlates with malignancy. Hypoxia activates hypoxia-inducible factor (HIF)-1α by inhibiting HIF-1α prolyl hydroxylation, which promotes glycolytic energy metabolism, vasculogenesis and angiogenesis, whereas HIF-1α is degraded by the HIF prolyl hydroxylase under normoxic conditions. We focus this review on the links between the activated Wnt/β-catenin pathway and the mechanisms underlying vasculogenesis and angiogenesis through HIF-1α under normoxic conditions in gliomas...
August 19, 2017: Reviews in the Neurosciences
https://www.readbyqxmd.com/read/28821596/hypoxia-decreases-creatine-uptake-in-cardiomyocytes-while-creatine-supplementation-enhances-hif-activation
#3
Lucia Santacruz, Antonio Jose Luis Arciniegas, Marcus Darrabie, Jose G Mantilla, Rebecca M Baron, Dawn E Bowles, Rajashree Mishra, Danny O Jacobs
Creatine (Cr), phosphocreatine (PCr), and creatine kinases (CK) comprise an energy shuttle linking ATP production in mitochondria with cellular consumption sites. Myocytes cannot synthesize Cr: these cells depend on uptake across the cell membrane by a specialized creatine transporter (CrT) to maintain intracellular Cr levels. Hypoxia interferes with energy metabolism, including the activity of the creatine energy shuttle, and therefore affects intracellular ATP and PCr levels. Here, we report that exposing cultured cardiomyocytes to low oxygen levels rapidly diminishes Cr transport by decreasing Vmax and Km Pharmacological activation of AMP-activated kinase (AMPK) abrogated the reduction in Cr transport caused by hypoxia...
August 2017: Physiological Reports
https://www.readbyqxmd.com/read/28820953/a-fluorescence-based-high-throughput-assay-for-the-identification-of-anticancer-reagents-targeting-fructose-1-6-bisphosphate-aldolase
#4
Eun Jeong Cho, Ashwini K Devkota, Gabriel Stancu, Ramakrishna Edupunganti, Garth Powis, Kevin N Dalby
A high rate of glycolysis, which supplies energy and materials for anabolism, is observed in a wide range of tumor cells, making it a potential pathway to control cancer growth. ALDOA is a multifunctional enzyme in the glycolytic pathway and also promotes HIF-1α, which is of importance in hypoxic solid tumors. The current method for assaying ALDOA activity involves monitoring the consumption of NADH in vitro using absorbance or intrinsic fluorescence via a coupled enzymatic reaction. Here, we report the development of a homogeneous biochemical assay that can overcome limitations of current methods, in particular for the application of high-throughput drug screening...
August 1, 2017: SLAS Discovery
https://www.readbyqxmd.com/read/28820398/chronic-kidney-disease-leads-to-hypoxia-inducible-factor-1alpha-to-hypoxia-inducible-factor-2alpha-switch-in-the-gastrocnemius-muscle
#5
M Flisinski, E Wisniewska-Chudy, A Brymora, A Stefanska, P Strozecki, J Manitius
Hipoxia inducible factor-1 and HIF-2 are responsible for the adaptation of cell metabolism to hypoxia. Previously, a more severe capillary rarefaction was found in locomotor than in postural muscles of uremic animals. The aim of this study was to analyze the expression patterns of HIF and prolyl hydroxylases (PHDs) in functionally different skeletal muscles in uremic rats, an experimental model of chronic kidney disease (CKD). Rats were randomized to sham operation - CON, uninephrectomy - CKD1/2 or subtotal nephrectomy - CKD5/6...
June 2017: Journal of Physiology and Pharmacology: An Official Journal of the Polish Physiological Society
https://www.readbyqxmd.com/read/28819918/network-analysis-of-se-and-zn-related-proteins-in-the-serum-proteomics-expression-profile-of-the-endemic-dilated-cardiomyopathy-keshan-disease
#6
Sen Wang, Yanyan Lv, Yingting Wang, Peiru Du, Wuhong Tan, Mikko J Lammi, Xiong Guo
Keshan disease (KD) is an endemic cardiomyopathy with high mortality. Selenium (Se) and zinc (Zn) deficiencies are closely related to KD. The molecular mechanism of KD pathogenesis is still unclear. There are only few studies on the interaction of trace elements and proteins associated with the pathogenesis of KD. In this study, isobaric tags for relative and absolute quantitation (iTRAQ)-coupled two-dimensional liquid chromatography tandem mass spectrometry (2DLC-MS/MS) technique analysis was used to analyze the differential expression of proteins from serum samples...
August 18, 2017: Biological Trace Element Research
https://www.readbyqxmd.com/read/28819544/hypoxia-downregulates-mapk-erk-but-not-stat3-signaling-in-ros-dependent-and-hif-1-independent-manners-in-mouse-embryonic-stem-cells
#7
Jan Kučera, Julie Netušilová, Stanislava Sladeček, Martina Lánová, Ondřej Vašíček, Kateřina Štefková, Jarmila Navrátilová, Lukáš Kubala, Jiří Pacherník
Hypoxia is involved in the regulation of stem cell fate, and hypoxia-inducible factor 1 (HIF-1) is the master regulator of hypoxic response. Here, we focus on the effect of hypoxia on intracellular signaling pathways responsible for mouse embryonic stem (ES) cell maintenance. We employed wild-type and HIF-1α-deficient ES cells to investigate hypoxic response in the ERK, Akt, and STAT3 pathways. Cultivation in 1% O2 for 24 h resulted in the strong dephosphorylation of ERK and its upstream kinases and to a lesser extent of Akt in an HIF-1-independent manner, while STAT3 phosphorylation remained unaffected...
2017: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/28819379/hypoxia-inducible-factor-1-alpha-correlates-with-tumor-associated-macrophages-infiltration-influences-survival-of-gastric-cancer-patients
#8
Wei-Jie Zhang, Cheng Chen, Zhi-Hua Zhou, Shan-Ting Gao, Teong Jin Tee, Liu-Qing Yang, Yuan-Yuan Xu, Tao-Hong Pang, Xin-Yun Xu, Qi Sun, Min Feng, Hao Wang, Chun-Lei Lu, Guo-Zhong Wu, Sheng Wu, Wen-Xian Guan, Gui-Fang Xu
Background: Hypoxia was a common feature for accelerating tumor metastasis by both inducting epithelial-mesenchymal transition (EMT) of tumor cells and polarization of tumor-associated macrophages (TAMs). The association and roles between hypoxia, EMT and TAMs in the biological behavior of gastric cancer (GC) for the time being recurrence is unclear. Material and methods: hypoixa by expression of hypoxia-inducible factor-1 alpha (HIF-1α), polarized functional status of infiltrated TAMs by immunohistochemical staining of CD68 and CD163, and the expression of E-cadherin as EMT property had been evaluated in 236 patients consecutive with histologically confirmed GC...
2017: Journal of Cancer
https://www.readbyqxmd.com/read/28819378/hif-is-not-essential-for-suppression-of-experimental-tumor-growth-by-mtor-inhibition
#9
Karl X Knaup, Regina Guenther, Johanna Stoeckert, Juliana M Monti, Kai-Uwe Eckardt, Michael S Wiesener
The Hypoxia Inducible Transcription Factor (HIF) is the master regulator of cellular response to hypoxic adaptation. Solid tumors inevitably harbour hypoxic regions with subsequent stabilization and activation of HIF and HIF target genes due to poor vascularization and rapid growth. The mammalian target of rapamycin (mTOR) is a global regulator of cellular growth and proliferation, which can also regulate HIF expression independantly of hypoxia via specific activation of cellular translation and transcription...
2017: Journal of Cancer
https://www.readbyqxmd.com/read/28819298/transcriptome-based-network-analysis-reveals-renal-cell-type-specific-dysregulation-of-hypoxia-associated-transcripts
#10
Natallia Shved, Gregor Warsow, Felix Eichinger, David Hoogewijs, Simone Brandt, Peter Wild, Matthias Kretzler, Clemens D Cohen, Maja T Lindenmeyer
Accumulating evidence suggests that dysregulation of hypoxia-regulated transcriptional mechanisms is involved in development of chronic kidney diseases (CKD). However, it remains unclear how hypoxia-induced transcription factors (HIFs) and subsequent biological processes contribute to CKD development and progression. In our study, genome-wide expression profiles of more than 200 renal biopsies from patients with different CKD stages revealed significant correlation of HIF-target genes with eGFR in glomeruli and tubulointerstitium...
August 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28819223/levobuipivacaine-induced-dissemination-of-a549-lung-cancer-cells
#11
Shun-Ming Chan, Bo-Feng Lin, Chih-Shung Wong, Wen-Ting Chuang, Yu-Ting Chou, Zhi-Fu Wu
While anaesthetics are frequently used on cancer patients during surgical procedures, their consequence on cancer progression remains to be elucidated. In this study, we sought to investigate the influence of local anesthetics on lung cancer cell dissemination in vitro and in vivo. A549 human non-small lung cancer cells were treated with various local anaesthetics including ropivacaine, lidocaine, levobupivacaine and bupivacaine. Cell barrier property was assessed using an electric cell-substrate impedance sensing (ECIS) system...
August 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28819164/hypoxia-triggers-ifn-i-production-in-muscle-implications-in-dermatomyositis
#12
Noemí De Luna, Xavier Suárez-Calvet, Cinta Lleixà, Jordi Diaz-Manera, Montse Olivé, Isabel Illa, Eduard Gallardo
Dermatomyositis is an inflammatory myopathy characterized by symmetrical proximal muscle weakness and skin changes. Muscle biopsy hallmarks include perifascicular atrophy, loss of intramuscular capillaries, perivascular and perimysial inflammation and the overexpression of IFN-inducible genes. Among them, the retinoic-acid inducible gene 1 (RIG-I) is specifically overexpressed in perifascicular areas of dermatomyositis muscle. The aim of this work was to study if RIG-I expression may be modulated by hypoxia using an in vitro approach...
August 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28818871/sexual-dimorphism-of-the-pulmonary-transcriptome-in-neonatal-hyperoxic-lung-injury-identification-of-angiogenesis-as-a-key-pathway
#13
Cristian Coarfa, Yuhao Zhang, Suman Maity, Dimuthu Perera, Weiwu Jiang, Lihua Wang, Xanthi Couroucli, Bhagavatula Moorthy, Krithika Lingappan
Bronchopulmonary dysplasia (BPD) is characterized by impaired alveolar secondary septation and vascular growth. Exposure to high concentrations of oxygen (hyperoxia) contributes to the development of BPD. Male sex is considered an independent risk factor for the development of BPD. The reasons underlying sexually dimorphic outcomes in premature neonates are not known. We hypothesized that sex-specific modulation of biological processes in the lung under hyperoxic conditions, contributes to sex-based differences...
August 17, 2017: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/28817659/resveratrol-improves-alcoholic-fatty-liver-disease-by-downregulating-hif-1%C3%AE-expression-and-mitochondrial-ros-production
#14
Zhenhua Ma, Yangmin Zhang, Qingchun Li, Meng Xu, Jigang Bai, Shengli Wu
Oxidative stress has been demonstrated to be involved in the etiology of alcoholic fatty liver disease (AFLD). Previous studies had demonstrated that resveratrol (RES) could reduce oxidative stress by different mechanisms. However, the effect of RES on alcohol-induced fatty liver remains unclear. In the present study, a total of 48 male SD rats were divided into three groups: Control, AFLD, and RES groups. Rats were administered with either nothing or 65% vol/vol alcohol (5 ml/kg/day in the first three days, and then 10 ml/kg/day in the following days) with or without RES supplementation (250 mg/kg/day) for 4 weeks...
2017: PloS One
https://www.readbyqxmd.com/read/28817179/autophagy-induction-plays-a-protective-role-against-hypoxic-stress-in-human-dental-pulp-cells
#15
Sam-Young Park, Eun-Gene Sun, Yeonju Lee, Min-Seok Kim, Jae Hyung Kim, Won-Jae Kim, Ji-Yeon Jung
Human dental pulp exposed to hypoxic conditions induces cell death accompanied by autophagy. However, the role of hypoxia-induced autophagy in human dental pulp cells (HDPCs) is unclear. The present study aimed to investigate the role of autophagy in hypoxia-induced apoptosis of HDPCs. Cobalt chloride (CoCl2 ) treated HDPCs, to mimic hypoxic conditions, decreased cell viability. Also, apoptosis-related signal molecules, cleaved caspase-3 and PARP levels, were enhanced in CoCl2 -treated HDPCs. HDPCs exposed to CoCl2 also promoted autophagy, showing upregulated p62 and microtubule-associated protein 1 light chain 3 (LC3)-II levels, typical autophagic markers, and increased acidic autophagolysosomal vacuoles...
August 17, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28817115/administration-of-follicle-stimulating-hormone-induces-autophagy-via-upregulation-of-hif-1%C3%AE-in-mouse-granulosa-cells
#16
Jilong Zhou, Wang Yao, Chengyu Li, Wangjun Wu, Qifa Li, Honglin Liu
Recent studies reported the important role of autophagy in follicular development. However, the underlying molecular mechanisms remain elusive. In this study, we investigated the effect of follicle-stimulating hormone (FSH) on mouse granulosa cells (MGCs). Results indicated that autophagy was induced by FSH, which is known to be the dominant hormone regulating follicular development and granulosa cell (GC) proliferation. The activation of mammalian target of rapamycin (mTOR), a master regulator of autophagy, was inhibited during the process of MGC autophagy...
August 17, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28816009/protective-effect-of-atazanavir-sulfate-against-pulmonary-fibrosis-in-vivo-and-in-vitro
#17
Shina Song, Yunxia Ji, Guanghua Zhang, Xue Zhang, Bin Li, Defang Li, Wanglin Jiang
Atazanavir sulfate, an antiretroviral protease inhibitor, has been used to treat HIV/AIDS, but its ability to serve as an anti-pulmonary fibrosis (PF) agent remains unknown. In this study, the effects of atazanavir sulfate on various aspects of PF were examined and CoCl2 was used to induce the hypoxia-mimicking condition in vitro, including epithelial-mesenchymal transition (EMT) in A549 cells, endothelial-mesenchymal transition (EndMT) in human pulmonary microvascular endothelial cells (HPMECs), proliferation in human lung fibroblasts (HLF-1) and potential protective effects in human type I alveolar epithelial cells (AT I)...
August 16, 2017: Basic & Clinical Pharmacology & Toxicology
https://www.readbyqxmd.com/read/28814833/markers-of-oxidative-nitrosative-stress-and-inflammation-in-lung-tissue-of-rats-exposed-to-different-intravenous-iron-compounds
#18
Jorge E Toblli, Gabriel Cao, Jorge F Giani, Fernando P Dominici, Margarita Angerosa
Iron deficiency anemia is a frequent complication in clinical conditions such as chronic kidney disease, chronic heart failure, inflammatory bowel disease, cancer, and excessive blood loss. Given the ability of iron to catalyze redox reactions, iron therapy can be associated with oxidative stress. The lung is uniquely susceptible to oxidative stress, and little is known about the effects of intravenous iron treatment in this organ. This study characterized changes in markers of oxidative/nitrosative stress and inflammation in the lung of non-iron deficient, non-anemic rats treated with five weekly doses (40 mg iron per kg body weight) of low molecular weight iron dextran (LMWID), iron sucrose (IS), ferric carboxymaltose (FCM), ferumoxytol (FMX), iron isomaltoside 1000 (IIM), or saline (control)...
2017: Drug Design, Development and Therapy
https://www.readbyqxmd.com/read/28814529/selective-hif-1-regulation-under-nonhypoxic-conditions-by-the-p42-p44-map-kinase-inhibitor-pd184161
#19
Maroua Jalouli, Sophie Mokas, Catherine A Turgeon, Laurent Lamalice, Darren E Richard
Hypoxia-inducible factor-1 (HIF-1) is a key gene regulator for cellular adaptation to low oxygen. In addition to hypoxia, several nonhypoxic stimuli, including hormones and growth factors, are an essential part for cell-specific HIF-1 regulation. Our studies have highlighted angiotensin II (AngII), a vasoactive hormone, as a potent HIF-1 activator in vascular smooth muscle cells (VSMC). AngII increases HIF-1 transcriptional activity by modulating specific signaling pathways. In VSMC, p42/p44 mitogen-activated protein kinase (MAPK) pathway activation is essential for HIF-1-mediated transcription during AngII treatment...
August 16, 2017: Molecular Pharmacology
https://www.readbyqxmd.com/read/28813675/cd44-interacts-with-hif-2%C3%AE-to-modulate-the-hypoxic-phenotype-of-perinecrotic-and-perivascular-glioma-cells
#20
Elinn Johansson, Elisa S Grassi, Vasiliki Pantazopoulou, Bei Tong, David Lindgren, Tracy J Berg, Elin J Pietras, Håkan Axelson, Alexander Pietras
Hypoxia-inducible factors enhance glioma stemness, and glioma stem cells have an amplified hypoxic response despite residing within a perivascular niche. Still, little is known about differential HIF regulation in stem versus bulk glioma cells. We show that the intracellular domain of stem cell marker CD44 (CD44ICD) is released at hypoxia, binds HIF-2α (but not HIF-1α), enhances HIF target gene activation, and is required for hypoxia-induced stemness in glioma. In a glioma mouse model, CD44 was restricted to hypoxic and perivascular tumor regions, and in human glioma, a hypoxia signature correlated with CD44...
August 15, 2017: Cell Reports
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