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erythropoiesis hypoxia

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https://www.readbyqxmd.com/read/29118187/jnk2-upregulates-hypoxia-inducible-factors-and-contributes-to-hypoxia-induced-erythropoiesis-and-pulmonary-hypertension
#1
Marc A Sala, Cong Chen, Qiao Zhang, Hanh Chi Do-Umehara, Wenjiao Wu, Alexander V Misharin, Gregory B Waypa, Deyu Fang, G R Scott Budinger, Shuwen Liu, Navdeep S Chandel, Paul T Schumacker, Jacob I Sznajder, Jing Liu
The hypoxic response is a stress response triggered by low-oxygen tension. Hypoxia-inducible factors (HIFs) play a prominent role in the pathobiology of hypoxia-associated conditions, including pulmonary hypertension (PH) and polycythemia. The c-Jun N-terminal protein kinase (JNK), a stress-activated protein kinase that consists of two ubiquitously expressed isoforms, JNK1 and JNK2, and a tissue-specific isoform, JNK3, has been shown to be activated by hypoxia. However, the physiological role of JNK1 and JNK2 in the hypoxic response remains elusive...
November 8, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29073196/fgf23-expression-in-rodents-is-directly-induced-via-erythropoietin-after-inhibition-of-hypoxia-inducible-factor-proline-hydroxylase
#2
Ingo Flamme, Peter Ellinghaus, Diana Urrego, Thilo Krüger
Plasma levels of FGF23 are increased in patients with chronic kidney disease. Beside its role in phosphate homeostasis, iron deficiency and anemia are associated with increased FGF23 plasma levels. Recently, FGF23 plasma levels were shown to be increased in mice after treatment with hypoxia inducible factor-proline hydroxylase (HIF-PH) inhibitors which are strong inducers of erythropoietin and erythropoiesis and are known to modulate iron uptake and availability. Therefore we investigated a potential context between expression of FGF23 and stimulation of erythropoiesis using a HIF-PH inhibitor and erythropoietin in rats...
2017: PloS One
https://www.readbyqxmd.com/read/29046642/cooperative-oxygen-sensing-by-the-kidney-and-carotid-body-in-blood-pressure-control
#3
Daniela Patinha, Wioletta Pijacka, Julian F R Paton, Maarten P Koeners
Oxygen sensing mechanisms are vital for homeostasis and survival. When oxygen levels are too low (hypoxia), blood flow has to be increased, metabolism reduced, or a combination of both, to counteract tissue damage. These adjustments are regulated by local, humoral, or neural reflex mechanisms. The kidney and the carotid body are both directly sensitive to falls in the partial pressure of oxygen and trigger reflex adjustments and thus act as oxygen sensors. We hypothesize a cooperative oxygen sensing function by both the kidney and carotid body to ensure maintenance of whole body blood flow and tissue oxygen homeostasis...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/29027252/the-athlete-s-hematological-response-to-hypoxia-a-meta-analysis-on-the-influence-of-altitude-exposure-on-key-biomarkers-of-erythropoiesis
#4
Louisa M Lobigs, Ken Sharpe, Laura A Garvican-Lewis, Christopher J Gore, Peter Peeling, Brian Dawson, Yorck O Schumacher
No abstract text is available yet for this article.
October 13, 2017: American Journal of Hematology
https://www.readbyqxmd.com/read/28978825/pathogenesis-and-treatment-of-anemia-in-chronic-kidney-disease
#5
Masaomi Nangaku
Chronic kidney disease leads to dysfunction of renal erythropoietin-producing cells, resulting in a decrease in erythrocyte production. A decrease in oxygen delivery to vital organs due to anemia results in worse quality of life and is associated with poor prognosis of the patients. Treatment with human recombinant erythropoietin or its improved version of erythropoiesis-stimulating agent (ESA) with a longer half-life is effective. However, some patients show hyporesponsiveness to ESA. Hyporesponsiveness to ESA, which can be induced by factors such as inflammation and uremic toxins, is associated with poor prognosis...
2017: [Rinshō Ketsueki] the Japanese Journal of Clinical Hematology
https://www.readbyqxmd.com/read/28974122/activation-of-hypoxia-inducible-factor-1%C3%AE-in-rat-brain-after-perinatal-anoxia-role-of-body-temperature
#6
Hanna Kletkiewicz, Malwina Hyjek, Krzysztof Jaworski, Anna Nowakowska, Justyna Rogalska
Transcriptional hypoxia-inducible factor-1α (HIF-1α) plays the fundamental role in adaptive processes in response to hypoxia. Specific HIF-1α target genes are involved in glycolysis, erythropoiesis and angiogenesis to promote survival. In our previous study we have demonstrated that naturally low body temperature of newborn rats protects them against damage due to perinatal hypoxia. Therefore, our experiments aimed at checking the effects of body temperature during simulated perinatal anoxia on subsequent changes of expression of HIF-1α and its specific target genes such as vascular endothelial growth factor (VEGF) and erythropoietin (EPO) in the rat brain...
October 23, 2017: International Journal of Hyperthermia
https://www.readbyqxmd.com/read/28973697/fenretinide-troglitazone-and-elmiron-add-to-weight-of-evidence-support-for-hemangiosarcoma-mode-of-action-from-studies-in-mice
#7
Jon C Cook, Leslie A Obert, Petra Koza-Taylor, Tim Coskran, Alan Opsahl, Daniel Ziemek, Marc Roy, Jessie Qian, Michael P Lawton, Kay Criswell
Pharmaceuticals and chemicals produce hemangiosarcomas (HS) in mice, often by nongenotoxic, proliferative mechanisms. A mode-of-action (MOA) for hemangiosarcoma was proposed based on information presented at an international workshop (Cohen et al., 2009). Five key elements of the MOA were articulated and included hypoxia, macrophage activation, increased angiogenic growth factors, dysregulated angiogenesis/erythropoiesis, and endothial cell proliferation. The goal of the current study was to add to the weight-of-evidence for the proposed MOA by assessing these key elements with three different compounds of varying potency for HS induction: fenretinide (high), troglitazone (intermediate), and elmiron (low)...
September 18, 2017: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/28904872/treatment-of-renal-anemia-erythropoiesis-stimulating-agents-and-beyond
#8
REVIEW
Patrick Biggar, Gheun-Ho Kim
Anemia, complicating the course of chronic kidney disease, is a significant parameter, whether interpreted as subjective impairment or an objective prognostic marker. Renal anemia is predominantly due to relative erythropoietin (EPO) deficiency. EPO inhibits apoptosis of erythrocyte precursors. Studies using EPO substitution have shown that increasing hemoglobin (Hb) levels up to 10-11 g/dL is associated with clinical improvement. However, it has not been unequivocally proven that further intensification of erythropoiesis stimulating agent (ESA) therapy actually leads to a comprehensive benefit for the patient, especially as ESAs are potentially associated with increased cerebro-cardiovascular events...
September 2017: Kidney Research and Clinical Practice
https://www.readbyqxmd.com/read/28777017/how-to-take-arms-against-central-apneas-in-heart-failure
#9
Chiara Borrelli, Alberto Aimo, Gianluca Mirizzi, Claudio Passino, Giuseppe Vergaro, Michele Emdin, Alberto Giannoni
Introduction Despite being a risk mediator in several observational studies, central apneas are currently orphan of treatment in heart failure. After the neutral effects on survival of two randomized controlled trials (RCTs) based on the use of positive airway pressure (the CANPAP and SERVE-HF trials), two alternative hypotheses have been formulated: 1) Periodic breathing/Cheyne-Stokes respiration (PB/CSR) in HF is protective. Indeed, the Naughton's hypothesis assumes that hyperventilation leads to increased cardiac output, lung volume, oxygen storage and reduced muscle sympathetic nerve activity, while central apnea to respiratory muscle rest and hypoxia-induced erythropoiesis...
August 23, 2017: Expert Review of Cardiovascular Therapy
https://www.readbyqxmd.com/read/28651951/prolyl-hydroxylase-domain-inhibitors-as-a-novel-therapeutic-approach-against-anemia-in-chronic-kidney-disease
#10
Mai Sugahara, Tetsuhiro Tanaka, Masaomi Nangaku
Anemia is a common complication of chronic kidney disease and is mainly caused by the inability of injured kidneys to produce adequate amounts of erythropoietin. Studies elucidating the regulation of erythropoietin production led to the identification of hypoxia-inducible factor (HIF), which activates the transcription of genes that mediate adaptive responses to hypoxia. HIF is a heterodimer that consists of an α and β subunit. While HIF-β is constitutively expressed, HIF-α is subjected to ubiquitination and proteasomal degradation under normoxic conditions...
August 2017: Kidney International
https://www.readbyqxmd.com/read/28641612/-expression-and-significance-of-hif-1%C3%AE-in-erythropoiesis-of-secondary-iron-overload-disease-after-irradiation-damage
#11
Yi Xing, Ming-Feng Zhao, Xiao-Li Cao, Xin Jin, Jie Chen, Ping Xu, Song-Nan Sui, Yan-Yu Jiang, Xiao-Yuan He
OBJECTIVE: To study the expression of hypoxia inducible factor 1α(HIF-1α) of iron-overloaded in irradiated mice and its effect on erythropoiesis. METHODS: Twenty mice were randomly divided into 4 groups: Ctrl (control group), IR (irradiation group), IO (irradiation + iron overload group), and RAPA (rapamycin treatment group). The iron overload model was verified. The CFU-E (colony forming unit-erythroid) and BFU-E(burst colony forming unit-erythroid) were cultured; flow cytometry was used to detect the ratios of early stage (Ter119(+)CD71(-)) to late stage (Ter119(+)CD71(+)) of primitive erythroblasts; RT-PCR was used to detect the mRNA expression of HIF-1α and its related signal molecules in bone marrow cells...
June 2017: Zhongguo Shi Yan Xue Ye Xue za Zhi
https://www.readbyqxmd.com/read/28629515/mutual-cross-talk-between-iron-homeostasis-and-erythropoiesis
#12
Ilona Rybinska, Gaetano Cairo
Iron is necessary for physiological processes essential for the activity of all cells, but the erythropoietic compartment is a privileged iron consumer. In fact, a considerable amount of iron is daily required for hemoglobin synthesis and erythroid cell proliferation. Therefore, a tight link exists between iron metabolism and erythropoiesis. The iron needed for hemoglobin synthesis is mainly ensured by inhibiting hepcidin expression, thereby increasing both ferroportin-mediated iron export from the duodenal absorptive cells and iron release from the reticuloendothelial cells that process old and/or damaged red blood cells...
2017: Vitamins and Hormones
https://www.readbyqxmd.com/read/28522758/regulation-of-erythropoiesis-after-normoxic-return-from-chronic-sustained-and-intermittent-hypoxia
#13
Jihyun Song, Krishna Sundar, Radhika Gangaraju, Josef T Prchal
Hypoxia increases erythropoiesis mediated by hypoxia-inducible transcription factors (HIF) which regulate erythropoietin (EPO) transcription. Neocytolysis is a physiological mechanism that corrects polycythemia from chronic sustained hypoxemia (CSH) by transient, preferential destruction of young RBCs after normoxia is restored. We showed that neocytolysis is caused by excessive mitochondrial-derived reactive oxygen species (ROS) in reticulocytes mediated by down-regulation of HIF-controlled BNIP3L regulated mitophagy and a decrease in RBC antioxidant catalase (CAT) in hypoxia-produced erythrocytes...
May 18, 2017: Journal of Applied Physiology
https://www.readbyqxmd.com/read/28483447/therapeutic-targeting-of-the-hif-oxygen-sensing-pathway-lessons-learned-from-clinical-studies
#14
REVIEW
Volker H Haase
The oxygen-sensitive hypoxia-inducible factor (HIF) pathway plays a central role in the control of erythropoiesis and iron metabolism. The discovery of prolyl hydroxylase domain (PHD) proteins as key regulators of HIF activity has led to the development of inhibitory compounds that are now in phase 3 clinical development for the treatment of renal anemia, a condition that is commonly found in patients with advanced chronic kidney disease. This review provides a concise overview of clinical effects associated with pharmacologic PHD inhibition and was written in memory of Professor Lorenz Poellinger...
July 15, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/28449418/hif-prolyl-hydroxylases-as-therapeutic-targets-in-erythropoiesis-and-iron-metabolism
#15
REVIEW
Volker H Haase
A classic response to systemic hypoxia is the increase in red blood cell production. This response is controlled by the prolyl hydroxylase domain/hypoxia-inducible factor (HIF) pathway, which regulates a broad spectrum of cellular functions. The discovery of this pathway as a key regulator of erythropoiesis has led to the development of small molecules that stimulate the production of endogenous erythropoietin and enhance iron metabolism. This review provides a concise overview of the cellular and molecular mechanisms that govern HIF-induced erythropoietic responses and provides an update on clinical experience with compounds that target HIF-prolyl hydroxylases for anemia therapy...
June 2017: Hemodialysis International
https://www.readbyqxmd.com/read/28443351/current-and-future-chemical-therapies-for-treating-anaemia-in-chronic-kidney-disease
#16
REVIEW
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: anemia, 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...
June 2017: Expert Opinion on Pharmacotherapy
https://www.readbyqxmd.com/read/28412770/anemia-in-chronic-kidney-disease
#17
Meredith A Atkinson, Bradley A Warady
Anemia is common and associated with adverse outcomes in children with chronic kidney disease (CKD). Many factors contribute to declining hemoglobin as CKD progresses, but impaired production of erythropoietin by failing kidneys is a central cause. Hepcidin-mediated iron restriction also contributes to anemia by downregulating both intestinal iron absorption and release of stored iron for erythropoiesis. The core components of anemia management remain erythropoiesis-stimulating agents (ESA) and iron supplementation, but despite these therapies, a substantial number of children remain anemic...
April 15, 2017: Pediatric Nephrology: Journal of the International Pediatric Nephrology Association
https://www.readbyqxmd.com/read/28410559/the-iron-y-of-iron-overload-and-iron-deficiency-in-chronic-obstructive-pulmonary-disease
#18
Suzanne M Cloonan, Sharon Mumby, Ian M Adcock, Augustine M K Choi, Kian Fan Chung, Gregory J Quinlan
No abstract text is available yet for this article.
November 1, 2017: American Journal of Respiratory and Critical Care Medicine
https://www.readbyqxmd.com/read/28376077/maternal-nutrient-restriction-in-guinea-pigs-leads-to-fetal-growth-restriction-with-evidence-for-chronic-hypoxia
#19
Alexander A Elias, Yohei Maki, Brad Matushewski, Karen Nygard, Timothy R H Regnault, Bryan S Richardson
BackgroundWe determined whether maternal nutrient restriction (MNR) in guinea pigs leading to fetal growth restriction (FGR) impacts markers for tissue hypoxia, implicating a mechanistic role for chronic hypoxia.MethodsGuinea pigs were fed ad libitum (Control) or 70% of the control diet before pregnancy, switching to 90% at mid-pregnancy (MNR). Near term, hypoxyprobe-1 (HP-1), a marker of tissue hypoxia, was injected into pregnant sows. Fetuses were then necropsied and liver, kidney, and placental tissues were processed for erythropoietin (EPO), EPO-receptor (EPOR), and vascular endothelial growth factor (VEGF) protein levels, and for HP-1 immunoreactivity (IR)...
July 2017: Pediatric Research
https://www.readbyqxmd.com/read/28371815/phase-2-studies-of-oral-hypoxia-inducible-factor-prolyl-hydroxylase-inhibitor-fg-4592-for-treatment-of-anemia-in-china
#20
Nan Chen, Jiaqi Qian, Jianghua Chen, Xueqing Yu, Changlin Mei, Chuanming Hao, Gengru Jiang, Hongli Lin, Xinzhou Zhang, Li Zuo, Qiang He, Ping Fu, Xuemei Li, Dalvin Ni, Stefan Hemmerich, Cameron Liu, Lynda Szczech, Anatole Besarab, Thomas B Neff, Kin-Hung Peony Yu, Frank H Valone
Background: FG-4592 (roxadustat) is an oral hypoxia-inducible factor (HIF) prolyl hydroxylase inhibitor (HIF-PHI) promoting coordinated erythropoiesis through the transcription factor HIF. Two Phase 2 studies were conducted in China to explore the safety and efficacy of FG-4592 (USAN name: roxadustat, CDAN name: ), a HIF-PHI, in patients with anemia of chronic kidney disease (CKD), both patients who were dialysis-dependent (DD) and patients who were not dialysis-dependent (NDD). Methods: In the NDD study, 91 participants were randomized to low (1...
August 1, 2017: Nephrology, Dialysis, Transplantation
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