Modulation of hepcidin production during hypoxia-induced erythropoiesis in humans in vivo: data from the HIGHCARE project

Blood ◽  
2011 ◽  
Vol 117 (10) ◽  
pp. 2953-2959 ◽  
Author(s):  
Alberto Piperno ◽  
Stefania Galimberti ◽  
Raffaella Mariani ◽  
Sara Pelucchi ◽  
Giulia Ravasi ◽  
...  
Keyword(s):  
Sea Level ◽  
Serum Ferritin ◽  
Iron Acquisition ◽  
Acute Hypoxia ◽  
Hypoxia Exposure ◽  
Oxygen Homeostasis ◽  
Iron Supply ◽  
Serum Hepcidin ◽  
Acute And Chronic Exposure

AbstractIron is tightly connected to oxygen homeostasis and erythropoiesis. Our aim was to better understand how hypoxia regulates iron acquisition for erythropoiesis in humans, a topic relevant to common hypoxia-related disorders. Forty-seven healthy volunteers participated in the HIGHCARE project. Blood samples were collected at sea level and after acute and chronic exposure to high altitude (3400-5400 m above sea level). We investigated the modifications in hematocrit, serum iron indices, erythropoietin, markers of erythropoietic activity, interleukin-6, and serum hepcidin. Hepcidin decreased within 40 hours after acute hypoxia exposure (P < .05) at 3400 m, reaching the lowest level at 5400 m (80% reduction). Erythropoietin significantly increased (P < .001) within 16 hours after hypoxia exposure followed by a marked erythropoietic response supported by the increased iron supply. Growth differentiation factor-15 progressively increased during the study period. Serum ferritin showed a very rapid decrease, suggesting the existence of hypoxia-dependent mechanism(s) regulating storage iron mobilization. The strong correlation between serum ferritin and hepcidin at each point during the study indicates that iron itself or the kinetics of iron use in response to hypoxia may signal hepcidin down-regulation. The combined and significant changes in other variables probably contribute to the suppression of hepcidin in this setting.

scholarly journals Metabolomic Analysis of Carbohydrate and Amino Acid Changes Induced by Hypoxia in Naked Mole-Rat Brain and Liver

Metabolites ◽  
2022 ◽  
Vol 12 (1) ◽  
pp. 56
Author(s):  
Hang Cheng ◽  
Yiming (Amy) Qin ◽  
Rashpal Dhillon ◽  
James Dowell ◽  
John M. Denu ◽  
...  
Keyword(s):  
Carbohydrate Metabolism ◽  
Energy Demand ◽  
Acute Hypoxia ◽  
Tissue Level ◽  
Heterocephalus Glaber ◽  
Hypoxia Exposure ◽  
Multiple Strategies ◽  
Mole Rat ◽  
Rat Brain And Liver

Hypoxia poses a major physiological challenge for mammals and has significant impacts on cellular and systemic metabolism. As with many other small rodents, naked mole-rats (NMRs; Heterocephalus glaber), who are among the most hypoxia-tolerant mammals, respond to hypoxia by supressing energy demand (i.e., through a reduction in metabolic rate mediated by a variety of cell- and tissue-level strategies), and altering metabolic fuel use to rely primarily on carbohydrates. However, little is known regarding specific metabolite changes that underlie these responses. We hypothesized that NMR tissues utilize multiple strategies in responding to acute hypoxia, including the modulation of signalling pathways to reduce anabolism and reprogram carbohydrate metabolism. To address this question, we evaluated changes of 64 metabolites in NMR brain and liver following in vivo hypoxia exposure (7% O2, 4 h). We also examined changes in matched tissues from similarly treated hypoxia-intolerant mice. We report that, following exposure to in vivo hypoxia: (1) phenylalanine, tyrosine and tryptophan anabolism are supressed both in NMR brain and liver; (2) carbohydrate metabolism is reprogramed in NMR brain and liver, but in a divergent manner; (3) redox state is significantly altered in NMR brain; and (4) the AMP/ATP ratio is elevated in liver. Overall, our results suggest that hypoxia induces significant metabolic remodelling in NMR brain and liver via alterations of multiple metabolic pathways.

Serum Hepcidin: Its Correlation with Serum Ferritin, Serum Iron and Hemoglobin in Patients of Iron Deficiency Anemia

2015 ◽  
Vol 14 (2) ◽  
pp. 105-113
Author(s):  
Sajjad H. Naqvi ◽  
Syed Faizan-ul-Hassan Naqvi ◽  
Iftikhar H. Naqvi ◽  
Muhammad Farhan ◽  
Tanveer Abbas ◽  
...  
Keyword(s):  
Iron Deficiency ◽  
Iron Deficiency Anemia ◽  
Serum Ferritin ◽  
Serum Iron ◽  
Deficiency Anemia ◽  
Serum Hepcidin

Relation of Serum Ferritin Level with Serum Hepcidin and Fucose Levels in Children with β-Thalassemia Major

Hemoglobin ◽  
2021 ◽  
Vol 45 (1) ◽  
pp. 69-73
Author(s):  
Salah H. AL-Zuhairy ◽  
Mohammed A. Darweesh ◽  
Mohammed A-M. Othman
Keyword(s):  
Serum Ferritin ◽  
Serum Ferritin Level ◽  
Ferritin Level ◽  
Thalassemia Major ◽  
Serum Hepcidin

scholarly journals Staphylococcus aureus Serves as an Iron Source for Pseudomonas aeruginosa during In Vivo Coculture

2005 ◽  
Vol 187 (2) ◽  
pp. 554-566 ◽  
Author(s):  
Lauren M. Mashburn ◽  
Amy M. Jett ◽  
Darrin R. Akins ◽  
Marvin Whiteley
Keyword(s):  
Staphylococcus Aureus ◽  
Pseudomonas Aeruginosa ◽  
Pathogenic Bacteria ◽  
Iron Acquisition ◽  
Low Oxygen ◽  
Dialysis Membrane ◽  
Opportunistic Human Pathogen ◽  
The Impact

ABSTRACT Pseudomonas aeruginosa is a gram-negative opportunistic human pathogen often infecting the lungs of individuals with the heritable disease cystic fibrosis and the peritoneum of individuals undergoing continuous ambulatory peritoneal dialysis. Often these infections are not caused by colonization with P. aeruginosa alone but instead by a consortium of pathogenic bacteria. Little is known about growth and persistence of P. aeruginosa in vivo, and less is known about the impact of coinfecting bacteria on P. aeruginosa pathogenesis and physiology. In this study, a rat dialysis membrane peritoneal model was used to evaluate the in vivo transcriptome of P. aeruginosa in monoculture and in coculture with Staphylococcus aureus. Monoculture results indicate that approximately 5% of all P. aeruginosa genes are differentially regulated during growth in vivo compared to in vitro controls. Included in this analysis are genes important for iron acquisition and growth in low-oxygen environments. The presence of S. aureus caused decreased transcription of P. aeruginosa iron-regulated genes during in vivo coculture, indicating that the presence of S. aureus increases usable iron for P. aeruginosa in this environment. We propose a model where P. aeruginosa lyses S. aureus and uses released iron for growth in low-iron environments.

Vitamin E prevents hypobaric hypoxia-induced mitochondrial dysfunction in skeletal muscle

2007 ◽  
Vol 113 (12) ◽  
pp. 459-466 ◽  
Author(s):  
José Magalhães ◽  
Rita Ferreira ◽  
Maria J. Neuparth ◽  
Paulo J. Oliveira ◽  
Franklim Marques ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Vitamin E ◽  
Mitochondrial Dysfunction ◽  
Hypobaric Hypoxia ◽  
Mitochondrial Membrane ◽  
Mitochondrial Protein ◽  
Membrane Integrity ◽  
Outer Mitochondrial Membrane ◽  
Hypoxia Exposure

In the present study, the effect of vitamin E (α-tocopherol) on mice skeletal muscle mitochondrial dysfunction and oxidative damage induced by an in vivo acute and severe hypobaric hypoxic insult (48 h at a barometric pressure equivalent to 8500 m) has been investigated. Male mice (n=24) were randomly divided into the following four groups (n=6): control (C), hypoxia (H), vitamin E (VE; 60 mg/kg of body weight intraperitoneally, three times/week for 3 weeks) and hypoxia+VE (HVE). A significant increase in mitochondrial protein CGs (carbonyl groups) was found in the H group compared with the C group. Confirming previous observations from our group, hypoxia induced mitochondrial dysfunction, as identified by altered respiratory parameters. Hypoxia exposure increased Bax content and decreased the Bcl-2/Bax ratio, whereas Bcl-2 remained unchanged. Inner and outer mitochondrial membrane integrity were significantly affected by hypoxia exposure; however, vitamin E treatment attenuated the effect of hypoxia on mitochondrial oxidative phosphorylation and on the levels of CGs. Vitamin E supplementation also prevented the Bax and Bcl-2/Bax ratio impairments caused by hypoxia, as well as the decrease in inner and outer mitochondrial membrane integrity. In conclusion, the results suggest that vitamin E prevents the loss of mitochondrial integrity and function, as well as the increase in Bax content, which suggests that mitochondria are involved in increased cell death induced by severe hypobaric hypoxia in mice skeletal muscle.

Peptide Blocking Self-Polymerization of Extracellular Calcium-Sensing Receptor Attenuates Hypoxia-Induced Pulmonary Hypertension

Hypertension ◽  
2021 ◽  
Author(s):  
Rui Xiao ◽  
Shengquan Luo ◽  
Ting Zhang ◽  
Yankai Lv ◽  
Tao Wang ◽  
...  
Keyword(s):  
Pulmonary Hypertension ◽  
Disulfide Bonds ◽  
Acute Hypoxia ◽  
Extracellular Domain ◽  
Left Ventricular ◽  
Extracellular Calcium ◽  
Calcium Sensing Receptor ◽  
Calcium Sensing

Activation of the CaSR (extracellular calcium-sensing receptor) has been recognized as a critical mediator of hypoxia-induced pulmonary hypertension. Preventive targeting of the early initiating phase as well as downstream events after CaSR activation remains unexplored. As a representative of the G protein-coupled receptor family, CaSR polymerizes on cell surface upon stimulation. Immunoblotting together with MAL-PEG technique identified a reactive oxygen species-sensitive CaSR polymerization through its extracellular domain in pulmonary artery smooth muscle cells upon exposure to acute hypoxia. Fluorescence resonance energy transfer screening employing blocking peptides determined that cycteine129/131 residues in the extracellular domain of CaSR formed intermolecular disulfide bonds to promote CaSR polymerization. The monitoring of intracellular Ca 2+ signal highlighted the pivotal role of CaSR polymerization in its activation. In contrast, the blockade of disulfide bonds formation using a peptide decreased both CaSR and hypoxia-induced mitogenic factor expression as well as other hypoxic-related genes in vitro and in vivo and attenuated pulmonary hypertension development in rats. The blocking peptide did not affect systemic arterial oxygenation in vivo but inhibited acute hypoxia-induced pulmonary vasoconstriction. Pharmacokinetic analyses revealed a more efficient lung delivery of peptide by inhaled nebulizer compared to intravenous injection. In addition, the blocking peptide did not affect systemic arterial pressure, body weight, left ventricular function, liver, or kidney function or plasma Ca 2+ level. In conclusion, a peptide blocking CaSR polymerization reduces its hypoxia-induced activation and downstream events leading to pulmonary hypertension and represents an attractive inhaled preventive alternative worthy of further development.

Maximal rate of blood lactate accumulation during exercise at altitude in humans

1995 ◽  
Vol 79 (1) ◽  
pp. 331-339 ◽  
Author(s):  
B. Grassi ◽  
G. Ferretti ◽  
B. Kayser ◽  
M. Marzorati ◽  
A. Colombini ◽  
...  
Keyword(s):  
Sea Level ◽  
Exercise Bout ◽  
Exercise Duration ◽  
Bicycle Ergometer ◽  
Glycolytic Flux ◽  
Maximal Rate ◽  
Lactate Accumulation ◽  
Blood Lactate Accumulation ◽  
The Individual

The lower peak lactate accumulation in blood ([La(b)]p) at altitude may be associated with a reduced maximal glycolytic flux. Based on certain assumptions, the latter can be indirectly evaluated in vivo, during short supramaximal exercises, by measuring the maximal rate of lactate accumulation in blood (delta [La(b)]max). delta [La(b)]max was determined on six white subjects at sea level (SL1), after approximately 1 wk (Alt1) and 4 wk (Alt2) of a 35-day sojourn at 5,050 m, and 1 wk after return to sea level (SL2). The subjects performed exercises of increasing duration (5, 15, 25, 35, 45 s or until exhaustion) on a bicycle ergometer at loads = 200% of the individual Wmax. The latter was previously determined in each condition as the greatest work rate that could be sustained for 2–4 min during an incremental exercise. Net [La(b)] accumulation (delta [La(b)]) was measured after each exercise bout. delta [La(b)] resulted to be linearly related to exercise duration. The slopes of the individual delta [La(b)] vs. exercise duration lines were taken as delta [La(b)]max. Exhaustion times were approximately 30–45 s in all conditions. [La(b)]p (in mM) during recovery after the exhaustive load was higher at SL1 (10.22 +/- 1.09; means +/- SD) than at Alt1 (5.08 +/- 0.82), Alt2 (8.13 +/- 2.67), and SL2 (8.18 +/- 1.43). delta [La(b)]max was lower at Alt1 (0.09 +/- 0.02) and at Alt2 (0.17 +/- 0.05) than at SL1 (0.25 +/- 0.05) and SL2 (0.23 +/- 0.06). Both [La(b)]p and delta [La(b)]max increased during acclimatization.

scholarly journals Aerobic and anaerobic metabolism for the zebrafish, Danio rerio, reared under normoxic and hypoxic conditions and exposed to acute hypoxia during development

2010 ◽  
Vol 70 (2) ◽  
pp. 425-434 ◽  
Author(s):  
WR Barrionuevo ◽  
MN Fernandes ◽  
O Rocha
Keyword(s):  
Danio Rerio ◽  
Anaerobic Metabolism ◽  
Developmental Stages ◽  
Acute Hypoxia ◽  
Lactate Concentration ◽  
Growth Delay ◽  
Hypoxic Conditions ◽  
Aerobic And Anaerobic ◽  
Mild Hypoxia

In order to verify the influence of chronic and acute ambient oxygen levels from egg to adult stage of the zebrafish, in vivo oxygen consumption (MO2), critical tensions of oxygen (Pcrit), heart rate (fH) and total body lactate concentration (Lc) were determined for Danio rerio (Hamilton, 1822) raised at 28 °C under normoxic (7.5 mgO2.L-1 or 80 mm.Hg-1) and hypoxic conditions (4.3 mgO2.L-1) and exposed to acute hypoxia during different developmental stages. Our findings confirmed that very early stages do not respond effectively to ambient acute hypoxia. However, after the stage corresponding to the age of 30 days, D. rerio was able to respond to acute hypoxia through effective physiological mechanisms involving aerobic and anaerobic metabolism. Such responses were more efficient for the fishes reared under hypoxia which showed that D. rerio survival capability increased during acclimation to mild hypoxia. Measurements of body mass and length showed that moderate hypoxia did not affect growth significantly until the fish reached the stage of 60 days. Moreover, a growth delay was verified for the hypoxic-reared animals. Also, the D. rerio eggs-to-larvae survival varied from 87.7 to 62.4% in animals reared under normoxia and mild hypoxia, respectively. However, the surviving animals raised under moderated hypoxia showed a better aptitude to regulate aerobic and anaerobic capacities when exposed to acute hypoxia.

scholarly journals Tibetans Retained Innate Ability Resistance to Acute Hypoxia after Long Period of Residing at Sea Level

2008 ◽  
Vol 58 (3) ◽  
pp. 167-172 ◽  
Author(s):  
Zhao-Nian Zhou ◽  
Jian-Guo Zhuang ◽  
Xiu-Feng Wu ◽  
Yi Zhang ◽  
Pipat Cherdrungsi
Keyword(s):  
Sea Level ◽  
Acute Hypoxia ◽  
Long Period ◽  
Innate Ability
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