Effect of graded normobaric hypoxia on Genome-wide expression in healthy individuals
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE265882 | GEO | 2024/12/30
REPOSITORIES: GEO
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Project description:Study objectives: Chronic obstructive pulmonary disease and obstructive sleep apnea overlap syndrome is associated with excess mortality, and outcomes are related to the degree of hypoxemia. People at high altitude are susceptible to periodic breathing, and hypoxia at altitude is associated with cardio-metabolic dysfunction. Hypoxemia in these scenarios may be described as superimposed sustained plus intermittent hypoxia, or overlap hypoxia (OH), the effects of which have not been investigated. We aimed to characterize the cardio-metabolic consequences of OH in mice. Methods: C57BL/6J mice were subjected to either sustained hypoxia (SH, FiO2=0.10), intermittent hypoxia (IH, FiO2=0.21 for 12 hours, and FiO2 oscillating between 0.21 and 0.06, 60 times/hour, for 12 hours), OH (FiO2=0.13 for 12 hours, and FiO2 oscillating between 0.13 and 0.06, 60 times/hour, for 12 hours), or room air (RA), n=8/group. Blood pressure and intraperitoneal glucose tolerance test were measured serially, and right ventricular systolic pressure (RVSP) was assessed. Results: Systolic blood pressure transiently increased in IH and OH relative to SH and RA. RVSP did not increase in IH, but increased in SH and OH by 52% (p<0.001) and 20% (p=0.001). Glucose disposal worsened in IH and improved in SH, with no change in OH. Serum LDL and VLDL increased in OH and SH, but not in IH. Hepatic oxidative stress increased in all hypoxic groups, with the highest increase in OH. Conclusions: Overlap hypoxia may represent a unique and deleterious cardio-metabolic stimulus, causing systemic and pulmonary hypertension, and without protective metabolic effects characteristic of sustained hypoxia.
2021-12-01 | GSE189958 | GEO
Project description:To determine hypoxia mediated changes in whole blood, normal C57Bl/10 mice were gradually exposed to a chronic hypoxic environment, equivalent to an altitude of 6500m, for 2 weeks in vivo. Control, age-matched mice were maintained under normoxic, normobaric conditions by exposing them to ambient air in Philadelphia (c. 50 mts above sea level). Purpose: To determine the expression profile of genes differentially expressed in mouse whole blood upon exposure to normobaric hypoxia in vivo. Methods: The hypoxic group consisting of 6 C57/BL10 mice was exposed to normobaric hypoxia, in a specially designed and hermetically closed hypoxic chamber, using a gas mixing system Pegas 4000 MF (Columbus Instruments, Ohio, USA). The oxygen level was decreased from 21% to 8% over a period of 14 days. 6 control mice were kept at normal oxygen and pressure levels by exposing them to ambient air in Philadelphia (c. 50 mts above sea level). RNA from whole blood was isolated, processed and used for microarray-based expression profiling. Profiles were generated for genes differentially expressed at control versus normobaric hypoxia in whole blood using a false discovery rate (FDR) of 0%. The Profile was validated by real-time quantitative reverse transcription-polymerase chain reaction (qPCR) on 2 biologically independent samples, not used for generating the profile. Results: The transcriptomes associated with normobaric hypoxia in whole blood were identified. We found 4723 genes that were differentially expressed in normobaric hypoxic whole blood compared to control with a 0% FDR and a 2 fold cutoff. Conclusion: Transcriptome level differences exist in the whole blood of animals subjected to normobaric hypoxia. Our definition of the normobaric hypoxia blood transcriptome provides insight into the functioning and response to hypoxia in whole blood.
2010-05-07 | E-GEOD-15894 | biostudies-arrayexpress
Project description:Objective: Athletes increasingly engage in repeated sprint training that consists of repeated short all-out effort interspersed by short periods of recovery. When performed in hypoxia (RSH), it may lead to greater training effects than in normoxia (RSN), however the underlying molecular mechanisms remain unclear. This study aimed at elucidating the effects of RSH on skeletal muscle oxidative and glycolytic adaptations as compared to RSN. Methods: Healthy young men performed nine repeated sprint training sessions in three weeks. Each training session consisted in six series of six sprints in either normoxia (FiO2 = 20.9%, RSN, n = 7) or normobaric hypoxia (FiO2 = 13.6%, RSH, n = 9). Before and after the training period, exercise performance was assessed by using repeated sprint ability (RSA) and Wingate tests. Vastus lateralis muscle biopsies were performed to investigate muscle metabolic adaptations using proteomic combined to western blotting analyses. Results: We observed similar improvements in RSA and Wingate tests in both RSH and RSN groups. Proteomic analysis revealed a decrease in several proteins involved in oxidative phosphorylation (OXPHOS) in both groups and this was confirmed with western blot showing significant reductions in complexes I and V protein levels. RSN and RSH increased protein levels of the glycolytic enzyme hexokinase II, while only RSH induced a significant increase in the glucose transporter 4 (GLUT4) protein levels, suggesting superior glycolytic adaptations in response to hypoxia. This phenotype is further supported by proteomics data showing significant increase of proteins involved in glycolysis. Our proteomics data showed in the RSH group a specific increase in several S100A family proteins, among which S100A13 was the most modified, a result confirmed by western blot. S100A proteins have recently been shown to accelerate glycolytic phenotype of cancer cells by activating the protein kinase B (Akt) pathway. Our data corroborate these findings by showing in RSH group increased Akt phosphorylation as well as increased levels of proteins related to Akt downstream effects such as enhanced translation. Conclusions: Altogether our data indicate that RSH, as compared to RSN, potentiates the muscle glycolytic phenotype, possibly through the activation of S100A13 and the Akt pathway.
2024-05-05 | PXD040779 | Pride
Project description:We report the application of single-molecule-based sequencing technology for high-throughput profiling of mouse pulmonary arteries (main, right and left extralobar branches) from C57BL/6 mice exposed to 6 weeks or hypoxia (FiO2 10%) and normoxia (FiO2%)
2021-08-25 | GSE182564 | GEO
Project description:Perinatal asphyxia is detrimental to the newborn baby and the use of supplemental oxygen during resuscitation may worsen the prognosis of these babies. The mechanism behind hyperoxic injury is not fully understood and our aim was to investigate four oxygen therapies following hypoxia and these effects on transcriptional activity. A microarray study was performed on 62 C57BL/6 mice randomized into four hypoxia groups (FiO2 0.08, 120 min) reoxygenated with FiO2 0.21, 0.40, 0.60 and 1.0 (30 min), and into two normoxia groups (FiO2 0.21,120 min) reoxygenated with FiO2 0.21 or 1.0, which served as control groups. A 150 min observation time in normoxia followed before animal sacrificing and lung, brain and eye tissue were stored in RNA Later before the microarray analysis were performed.
2013-03-13 | E-GEOD-32500 | biostudies-arrayexpress
Project description:Calorie restriction (CR) extends lifespan by modulating the mechanisms involved in aging. We quantified the hepatic proteome of male C57BL/6 mice exposed to graded levels of CR (0% to 40% CR) for three months, and evaluated which signaling pathways were most affected.
2023-10-24 | PXD033436 | Pride
Project description:The yeast cells were grown aerobically on galactose medium. At time zero (generation 0) the saprge gas was switched from air to O2-free N2 and samples were harvested after 0 (aerobic control), 0.04, 0.08, 0.13, 0.19, 0.25, 0.38, 0.5, 1, 2, 3, 4, 5 and 6 generations of anaerobic growth. After six generations, the saprge gas was switched back to air and samples were harvested at 6 (anaerobic control), 6.03, 6.06, 6.1, 6.13, 6.2, 6.3, 6.4, 6.6, 6.8, and 7.6 generations. Keywords: time-course
2006-06-30 | GSE2246 | GEO
Project description:The yeast cells were grown aerobically on glucose medium. At time zero (generation 0) the saprge gas was switched from air to O2-free N2 and samples were harvested after 0 (aerobic control), 0.04, 0.08, 0.13, 0.19, 0.25, 0.38, 0.5, 1, 2, 3, 4, 5 and 6 generations of anaerobic growth. After six generations, the saprge gas was switched back to air and samples were harvested at 6 (anaerobic control), 6.03, 6.06, 6.1, 6.13, 6.2, 6.3, 6.4, 6.6, 6.8, and 7.6 generations. Keywords: time-course
2006-06-30 | GSE2267 | GEO
Project description:The yeast cells were grown aerobically on glucose medium. At time zero (generation 0) the saprge gas was switched from air to O2-free N2 and samples were harvested after 0 (aerobic control), 0.04, 0.08, 0.13, 0.19, 0.25, 0.38, 0.5, 1, 2, 3, 4, 5 and 6 generations of anaerobic growth. After six generations, the saprge gas was switched back to air and samples were harvested at 6 (anaerobic control), 6.03, 6.06, 6.1, 6.13, 6.2, 6.3, 6.4, 6.6, 6.8, and 7.6 generations. Keywords: time-course
2010-06-11 | E-GEOD-2267 | biostudies-arrayexpress
Project description:The yeast cells were grown aerobically on galactose medium. At time zero (generation 0) the saprge gas was switched from air to O2-free N2 and samples were harvested after 0 (aerobic control), 0.04, 0.08, 0.13, 0.19, 0.25, 0.38, 0.5, 1, 2, 3, 4, 5 and 6 generations of anaerobic growth. After six generations, the saprge gas was switched back to air and samples were harvested at 6 (anaerobic control), 6.03, 6.06, 6.1, 6.13, 6.2, 6.3, 6.4, 6.6, 6.8, and 7.6 generations. Keywords: time-course
2010-06-11 | E-GEOD-2246 | biostudies-arrayexpress