Adaptation to Hypocapnia and its Role in Adaptation to Hypoxia

1974 ◽  
pp. 294-303
Author(s):  
Ralph H. Kellogg
Keyword(s):  
Adaptation To Hypoxia

LEVELS OF FREE PLASMA AMINO ACIDS UNDER ACUTE NORMOBARIC HYPOXIA IN VOLUNTEERS IN FASTED AND POSTPRANDIAL STATES

2020 ◽  
pp. 108-117
Author(s):  
A.A. Chernykh ◽  
N.N. Potolitsyna ◽  
E.A. Burykh ◽  
E.R. Boyko
Keyword(s):  
Amino Acids ◽  
Normobaric Hypoxia ◽  
Adaptation To Hypoxia ◽  
Plasma Amino Acids ◽  
Fed State ◽  
Metabolic Substrates ◽  
Overnight Fasting ◽  
Group 2 ◽  
Free Plasma ◽  
Group 1

The aim of the study was to assess the effect of acute normobaric hypoxia on free plasma amino acids (AA) in volunteers after overnight fasting and in the fed state. Materials and Methods. Group 1 (n=13, aged 22–32) participated in the study in the morning after overnight fasting. Group 2 (n=9, aged 22–32) took part in the study after a light fat-free breakfast. Acute normobaric hypoxia was achieved by breathing a hypoxic gas mixture (9 % O2 and 91 % N2) through a mask. According to the experimental protocol, blood sampling from the cubital vein was performed for analysis. Free plasma amino acids were analyzed using the Aracus amino acid analyzer. Results. Prior to the hypoxia onset, at the 5th and 20th minutes of hypoxia, no statistically significant differences in free AA levels were observed in the groups (p>0.05). At the 10th minute of hypoxia the levels of four AAs (serine, threonine, glutamine, and histidine) were significantly higher in Group 1 than in Group 2 (p<0.05). This was probably due to differences in functioning of several key “harmonizing” AA transporters (ASCT1 (SLC1A4), ASCT2 (SLC1A5) and LAT1 (SC7A5)), for which the AAs were metabolic substrates. It can be assumed, that such changes were caused by currently unclear mechanisms of fast regulation of AA transporter activity, associated with nutritional status. Conclusion. We believe that our findings may be important for providing better adaptation to hypoxia, and for more efficient correction of hypoxic negative effects. Keywords: acute normobaric hypoxia, free plasma amino acids, human. Цель исследования: изучить воздействие острой нормобарической гипоксии на метаболизм свободных аминокислот (АК) плазмы крови у добровольцев, участвовавших в исследовании натощак и после лёгкого завтрака. Материалы и методы. Первая группа добровольцев (22–32 года, n=13) участвовала в исследовании утром натощак, вторая группа (22–32 года, n=9) – через 2–3 ч после лёгкого безжирового завтрака. Гипоксия создавалась путём подачи через маску дыхательной смеси, содержащей 9 % О2 и 91 % N2. В соответствии с протоколом проводился периодический забор крови из локтевой вены для анализа. Оценка уровней свободных АК плазмы крови производилась с помощью аминокислотного анализатора Aracus. Результаты. До начала гипоксии, на 5-й и 20-й мин гипоксии уровни свободных АК в первой и второй группах значимо не различались (p>0,05). На 10-й мин гипоксии между первой и второй группами наблюдались статистически значимые различия уровней четырёх АК: глутамина, серина, треонина и гистидина (p<0,05). Это, вероятно, было обусловлено изменениями в работе «гармонизирующих» мембранных транспортёров (ASCT1 (SLC1A4), ASCT2 (SLC1A5) и LAT1 (SC7A5)), для которых эти АК являются обменными субстратами. Можно предположить, что данные изменения были опосредованы пока неясными механизмами быстрой регуляции активности этих транспортёров, зависящими от питания. Выводы. Мы полагаем, что полученные результаты могут иметь значение для обеспечения адаптации организма человека к острой гипоксии и эффективной коррекции последствий гипоксического воздействия. Ключевые слова: острая нормобарическая гипоксия, свободные аминокислоты плазмы крови, человек.

scholarly journals Hypoxia-Induced Cancer Cell Responses Driving Radioresistance of Hypoxic Tumors: Approaches to Targeting and Radiosensitizing

Cancers ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 1102
Author(s):  
Alexander E. Kabakov ◽  
Anna O. Yakimova
Keyword(s):  
Heat Shock ◽  
Tumor Cells ◽  
Cancer Cell ◽  
Epithelial Mesenchymal Transition ◽  
Liver Tumors ◽  
Oxygen Deficiency ◽  
Transarterial Embolization ◽  
Antiangiogenic Therapy ◽  
Adaptation To Hypoxia ◽  
Mesenchymal Transition

Within aggressive malignancies, there usually are the “hypoxic zones”—poorly vascularized regions where tumor cells undergo oxygen deficiency through inadequate blood supply. Besides, hypoxia may arise in tumors as a result of antiangiogenic therapy or transarterial embolization. Adapting to hypoxia, tumor cells acquire a hypoxia-resistant phenotype with the characteristic alterations in signaling, gene expression and metabolism. Both the lack of oxygen by itself and the hypoxia-responsive phenotypic modulations render tumor cells more radioresistant, so that hypoxic tumors are a serious challenge for radiotherapy. An understanding of causes of the radioresistance of hypoxic tumors would help to develop novel ways for overcoming this challenge. Molecular targets for and various approaches to radiosensitizing hypoxic tumors are considered in the present review. It is here analyzed how the hypoxia-induced cellular responses involving hypoxia-inducible factor-1, heat shock transcription factor 1, heat shock proteins, glucose-regulated proteins, epigenetic regulators, autophagy, energy metabolism reprogramming, epithelial–mesenchymal transition and exosome generation contribute to the radioresistance of hypoxic tumors or may be inhibited for attenuating this radioresistance. The pretreatments with a multitarget inhibition of the cancer cell adaptation to hypoxia seem to be a promising approach to sensitizing hypoxic carcinomas, gliomas, lymphomas, sarcomas to radiotherapy and, also, liver tumors to radioembolization.

scholarly journals Multi-omics analysis reveals contextual tumor suppressive and oncogenic gene modules within the acute hypoxic response

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Zdenek Andrysik ◽  
Heather Bender ◽  
Matthew D. Galbraith ◽  
Joaquin M. Espinosa
Keyword(s):  
Cancer Biology ◽  
Acute Hypoxia ◽  
Transcriptional Response ◽  
Adaptation To Hypoxia ◽  
Mtor Inhibition ◽  
Collagen Remodeling ◽  
Acute Response ◽  
Relative Contribution ◽  
Transcriptional Changes ◽  
Cancer Types

AbstractCellular adaptation to hypoxia is a hallmark of cancer, but the relative contribution of hypoxia-inducible factors (HIFs) versus other oxygen sensors to tumorigenesis is unclear. We employ a multi-omics pipeline including measurements of nascent RNA to characterize transcriptional changes upon acute hypoxia. We identify an immediate early transcriptional response that is strongly dependent on HIF1A and the kinase activity of its cofactor CDK8, includes indirect repression of MYC targets, and is highly conserved across cancer types. HIF1A drives this acute response via conserved high-occupancy enhancers. Genetic screen data indicates that, in normoxia, HIF1A displays strong cell-autonomous tumor suppressive effects through a gene module mediating mTOR inhibition. Conversely, in advanced malignancies, expression of a module of HIF1A targets involved in collagen remodeling is associated with poor prognosis across diverse cancer types. In this work, we provide a valuable resource for investigating context-dependent roles of HIF1A and its targets in cancer biology.

scholarly journals Aquaglyceroporin-3’s Expression and Cellular Localization Is Differentially Modulated by Hypoxia in Prostate Cancer Cell Lines

Cells ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 838
Author(s):  
Andreia de Almeida ◽  
Dimitris Parthimos ◽  
Holly Dew ◽  
Oliver Smart ◽  
Marie Wiltshire ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cell Lines ◽  
Crucial Role ◽  
Cellular Localization ◽  
Texture Features ◽  
Stress Factors ◽  
Adaptation To Hypoxia ◽  
Machine Learning Classification ◽  
Hypoxia Exposure ◽  
Pc3 Cells

Aquaporins are required by cells to enable fast adaptation to volume and osmotic changes, as well as microenvironmental metabolic stimuli. Aquaglyceroporins play a crucial role in supplying cancer cells with glycerol for metabolic needs. Here, we show that AQP3 is differentially expressed in cells of a prostate cancer panel. AQP3 is located at the cell membrane and cytoplasm of LNCaP cell while being exclusively expressed in the cytoplasm of Du145 and PC3 cells. LNCaP cells show enhanced hypoxia growth; Du145 and PC3 cells display stress factors, indicating a crucial role for AQP3 at the plasma membrane in adaptation to hypoxia. Hypoxia, both acute and chronic affected AQP3′s cellular localization. These outcomes were validated using a machine learning classification approach of the three cell lines and of the six normoxic or hypoxic conditions. Classifiers trained on morphological features derived from cytoskeletal and nuclear labeling alongside corresponding texture features could uniquely identify each individual cell line and the corresponding hypoxia exposure. Cytoskeletal features were 70–90% accurate, while nuclear features allowed for 55–70% accuracy. Cellular texture features (73.9% accuracy) were a stronger predictor of the hypoxic load than the AQP3 distribution (60.3%).

scholarly journals Association of EGLN1 gene with high aerobic capacity of Peruvian Quechua at high altitude

2019 ◽  
Vol 116 (48) ◽  
pp. 24006-24011 ◽  
Author(s):  
Tom D. Brutsaert ◽  
Melisa Kiyamu ◽  
Gianpietro Elias Revollendo ◽  
Jenna L. Isherwood ◽  
Frank S. Lee ◽  
...  
Keyword(s):  
Natural Selection ◽  
Aerobic Capacity ◽  
Cellular Response ◽  
Hypoxia Inducible Factor ◽  
Total Sample ◽  
Causal Variant ◽  
Analysis Of Covariance ◽  
Adaptation To Hypoxia ◽  
Spurious Association ◽  
Factor Α

Highland native Andeans have resided at altitude for millennia. They display high aerobic capacity (VO2max) at altitude, which may be a reflection of genetic adaptation to hypoxia. Previous genomewide (GW) scans for natural selection have nominated Egl-9 homolog 1 gene (EGLN1) as a candidate gene. The encoded protein, EGLN1/PHD2, is an O2 sensor that controls levels of the Hypoxia Inducible Factor-α (HIF-α), which regulates the cellular response to hypoxia. From GW association and analysis of covariance performed on a total sample of 429 Peruvian Quechua and 94 US lowland referents, we identified 5 EGLN1 SNPs associated with higher VO2max (L⋅min−1 and mL⋅min−1⋅kg−1) in hypoxia (rs1769793, rs2064766, rs2437150, rs2491403, rs479200). For 4 of these SNPs, Quechua had the highest frequency of the advantageous (high VO2max) allele compared with 25 diverse lowland comparison populations from the 1000 Genomes Project. Genotype effects were substantial, with high versus low VO2max genotype categories differing by ∼11% (e.g., for rs1769793 SNP genotype TT = 34.2 mL⋅min−1⋅kg−1 vs. CC = 30.5 mL⋅min−1⋅kg−1). To guard against spurious association, we controlled for population stratification. Findings were replicated for EGLN1 SNP rs1769793 in an independent Andean sample collected in 2002. These findings contextualize previous reports of natural selection at EGLN1 in Andeans, and support the hypothesis that natural selection has increased the frequency of an EGLN1 causal variant that enhances O2 delivery or use during exercise at altitude in Peruvian Quechua.

Physiological aspects of the mitochondrial cyclosporin A-insensitive palmitate/Ca2+-induced pore: tissue specificity, age profile and dependence on the animal’s adaptation to hypoxia

2009 ◽  
Vol 41 (4) ◽  
pp. 395-401 ◽  
Author(s):  
Konstantin N. Belosludtsev ◽  
Nils-Erik L. Saris ◽  
Natalia V. Belosludtseva ◽  
Alexander S. Trudovishnikov ◽  
Lyudmila D. Lukyanova ◽  
...  
Keyword(s):  
Cyclosporin A ◽  
Tissue Specificity ◽  
Adaptation To Hypoxia ◽  
Age Profile

Temperature regulation in lizards: effects of hypoxia

1985 ◽  
Vol 248 (5) ◽  
pp. R595-R600 ◽  
Author(s):  
J. W. Hicks ◽  
S. C. Wood
Keyword(s):  
Body Temperature ◽  
Temperature Regulation ◽  
Adaptation To Hypoxia ◽  
Metabolic Demand ◽  
Reduced Body ◽  
Life Saving ◽  
Preferred Body Temperature ◽  
Rate Of Cooling ◽  
Temperature Exposure ◽  
Hypoxic Gas Mixture

Temperature regulation during external (lowered lung PO2) and internal hypoxia (anemia) was examined in four species of lizards. Exposure to a hypoxic gas mixture in a thermogradient resulted in the animals lowering their selected (preferred) body temperature. A 50% reduction in the O2 carrying capacity of the blood also reduced the selected body temperature. Lizards "shuttle" when forced to select a temperature either above or below their normal selected temperature. Exposure to hypoxia decreases the upper and lower exit temperatures during shuttling. Furthermore, a decrease in the inspired O2 causes the rate of heating to no longer exceed the rate of cooling as is normal. The behavioral reduction of body temperature and the altered neural and physiological aspects of temperature regulation appear to be generalized responses to impaired O2 transport and not PO2 per se. The reduced body temperature, by lowering metabolic demand, provides an effective, even life-saving, adaptation to hypoxia.

Role of erythropoietin in adaptation to hypoxia

1990 ◽  
Vol 46 (11-12) ◽  
pp. 1197-1201 ◽  
Author(s):  
H. Scholz ◽  
H. -J. Schurek ◽  
K. -U. Eckardt ◽  
C. Bauer
Keyword(s):  
Adaptation To Hypoxia

scholarly journals Molecular mechanisms of ischemic preconditioning in the kidney

2015 ◽  
Vol 309 (10) ◽  
pp. F821-F834 ◽  
Author(s):  
Pinelopi P. Kapitsinou ◽  
Volker H. Haase
Keyword(s):  
Molecular Mechanisms ◽  
Therapeutic Potential ◽  
Kidney Injury ◽  
Hypoxic Preconditioning ◽  
Adaptation To Hypoxia ◽  
High Morbidity ◽  
Nitric Oxide Signaling ◽  
Cellular Energy ◽  
Treatment And Prevention ◽  
Multiple Signaling

More effective therapeutic strategies for the prevention and treatment of acute kidney injury (AKI) are needed to improve the high morbidity and mortality associated with this frequently encountered clinical condition. Ischemic and/or hypoxic preconditioning attenuates susceptibility to ischemic injury, which results from both oxygen and nutrient deprivation and accounts for most cases of AKI. While multiple signaling pathways have been implicated in renoprotection, this review will focus on oxygen-regulated cellular and molecular responses that enhance the kidney's tolerance to ischemia and promote renal repair. Central mediators of cellular adaptation to hypoxia are hypoxia-inducible factors (HIFs). HIFs play a crucial role in ischemic/hypoxic preconditioning through the reprogramming of cellular energy metabolism, and by coordinating adenosine and nitric oxide signaling with antiapoptotic, oxidative stress, and immune responses. The therapeutic potential of HIF activation for the treatment and prevention of ischemic injuries will be critically examined in this review.

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