Effects of chronic hypoxia on Duchenne Muscular Dystrophy Drosophila melanogaster model
Ontology highlight
ABSTRACT:
ORGANISM(S): Drosophila melanogaster
PROVIDER: GSE15879 | GEO | 2010/07/31
SECONDARY ACCESSION(S): PRJNA117037
REPOSITORIES: GEO
Similar Datasets
Project description:In order to understand the chronic hypoxia (CH) effect upon the absence of dystrophin, Drosophila melanogaster wild type and the model for DMD (dmDys), in which all dystrophins expression was knocked out by iRNA, were exposed to high altitude hypoxia (hypobaric hypoxia) during a 16-day climbing period reaching the summit of Mount McKinley (6194 meters above sea level). Furthermore, dmDys and Drosophila wild type were exposed to normobaric hypoxia (hypoxic chamber) following the same oxygen levels observed during the climbing expedition and to normoxic conditions for comparison. Affymetrix GeneChip® profiling was performed for individual flies from each experimental group. CH-dmDys differentially expressed 1281 genes, whereas control group differentially expressed 57 genes. Eight heat shock protein genes detected in the CH-dmDys microarray study were down-regulated, instead of up-regulated as seen in wild type hypoxic flies. This result suggests a differential gene expression response to CH, which could affect muscle performance.These results suggest that dmDys is more sensitive to CH due to reduced muscle function and hypoxic stress response. In order to understand the chronic hypoxia (CH) effect upon the absence of dystrophin, Drosophila melanogaster wild type and the model for DMD (dmDys), in which all dystrophins expression was knocked out by iRNA, were exposed to high altitude hypoxia (hypobaric hypoxia) during a 16-day climbing period reaching the summit of Mount McKinley (6194 meters above sea level). Furthermore, dmDys and Drosophila wild type were exposed to normobaric hypoxia (hypoxic chamber) following the same oxygen levels observed during the climbing expedition and to normoxic conditions for comparison. Affymetrix GeneChip® profiling was performed for individual flies from each experimental group. CH-dmDys differentially expressed 1281 genes, whereas control group differentially expressed 57 genes. Eight heat shock protein genes detected in the CH-dmDys microarray study were down-regulated, instead of up-regulated as seen in wild type hypoxic flies. This result suggests a differential gene expression response to CH, which could affect muscle performance.These results suggest that dmDys is more sensitive to CH due to reduced muscle function and hypoxic stress response. Overall design: Adults wild type and dystrophic flies (3-5 days old) were exposed to hypobaric hypoxia for two weeks during the summer expedition to Mount McKinley, Alaska (6194 MASL). Another set of wild types and dystrophic flies were exposed to normobaric hypoxia according to the table I obtained during the climbing expedition. During the expedition, the flies were maintained in vials with regular molasses and covered by thermo isolation to avoid low temperature, keeping the temperature at 25C. The experiment performed in the laboratory also used vials with regular molasses and at 25C. Table I. Expedition log book for mount McKinley ascent. Information obtained during the ascent and summit of Mount McKinley, June 1st to June 16th of 2007. The oxygen pressure (PO2) was calculated from the barometric pressure. GNB means go and back from the mentioned point. DAY In order to understand the chronic hypoxia (CH) effect upon the absence of dystrophin, Drosophila melanogaster wild type and the model for DMD (dmDys), in which all dystrophins expression was knocked out by iRNA, were exposed to high altitude hypoxia (hypobaric hypoxia) during a 16-day climbing period reaching the summit of Mount McKinley (6194 meters above sea level). Furthermore, dmDys and Drosophila wild type were exposed to normobaric hypoxia (hypoxic chamber) following the same oxygen levels observed during the climbing expedition and to normoxic conditions for comparison. Affymetrix GeneChip® profiling was performed for individual flies from each experimental group. CH-dmDys differentially expressed 1281 genes, whereas control group differentially expressed 57 genes. Eight heat shock protein genes detected in the CH-dmDys microarray study were down-regulated, instead of up-regulated as seen in wild type hypoxic flies. This result suggests a differential gene expression response to CH, which could affect muscle performance.These results suggest that dmDys is more sensitive to CH due to reduced muscle function and hypoxic stress response. In order to understand the chronic hypoxia (CH) effect upon the absence of dystrophin, Drosophila melanogaster wild type and the model for DMD (dmDys), in which all dystrophins expression was knocked out by iRNA, were exposed to high altitude hypoxia (hypobaric hypoxia) during a 16-day climbing period reaching the summit of Mount McKinley (6194 meters above sea level). Furthermore, dmDys and Drosophila wild type were exposed to normobaric hypoxia (hypoxic chamber) following the same oxygen levels observed during the climbing expedition and to normoxic conditions for comparison. Affymetrix GeneChip® profiling was performed for individual flies from each experimental group. CH-dmDys differentially expressed 1281 genes, whereas control group differentially expressed 57 genes. Eight heat shock protein genes detected in the CH-dmDys microarray study were down-regulated, instead of up-regulated as seen in wild type hypoxic flies. This result suggests a differential gene expression response to CH, which could affect muscle performance.These results suggest that dmDys is more sensitive to CH due to reduced muscle function and hypoxic stress response. Overall design: Adults wild type and dystrophic flies (3-5 days old) were exposed to hypobaric hypoxia for two weeks during the summer expedition to Mount McKinley, Alaska (6194 MASL). Another set of wild types and dystrophic flies were exposed to normobaric hypoxia according to the table I obtained during the climbing expedition. During the expedition, the flies were maintained in vials with regular molasses and covered by thermo isolation to avoid low temperature, keeping the temperature at 25C. The experiment performed in the laboratory also used vials with regular molasses and at 25C. Table I. Expedition log book for mount McKinley ascent. Information obtained during the ascent and summit of Mount McKinley, June 1st to June 16th of 2007. The oxygen pressure (PO2) was calculated from the barometric pressure. GNB means go and back from the mentioned point. DAY LOCATION ALTITUDE m PO2 mmHg (%) 1 Base Camp 2200 123.6 (16.3%) 2 Base Camp 2200 123.6 (16.3%) 3 Base Camp 2200 123.6 (16.3%) 4 Ski Hill 2400 120.7 (15.9%) 5 Kahiltna Pass 2950 113.0 (14.9%) 6 Motorcycle Hill 3350 107.7 (14.2%) 7 Motorcycle Hill 3350 107.7 (14.2%) 8 GNB from Motorcycle 4150 (5 hours) 97.7 (12.9%) 9 Medical Camp 4350 95.3 (12.5%) 10 GNB from Medical Camp 4150 (5 hours) 97.7 (12.9%) 11 Medical Camp 4350 95.3 (12.5%) 12 GNB from Medical Camp 4900 89.0 (11.7%) 13 Medical Camp 4350 95.3 (12.5%) 14 High Camp 5250 85.1 (11.2%) 15 Summit 6194 (0.3 hours) 75.4 (9.9%) 16 High Camp 5250 85.1 (11.2%)
2010-07-31 | E-GEOD-15879 | biostudies-arrayexpress
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:To determine hypoxia mediated changes in whole blood, normal swiss webster mice were gradually exposed to a chronic hypobaric hypoxic environment up to 8500m, for 2 weeks in vivo. Control, age-matched mice were maintained under normoxic conditions in Kathmandu (c. 1300 mts above sea level). Purpose: To examine and characterize the expression profile of genes expressed at hypobaric hypoxia on Mt. Everest of whole blood in comparison to the control. Methods: At the beginning of the experiment mice were divided into two groups, control (room condition, Kathmandu, Nepal) and hypoxic (hypoxic condition). For conditioning, the hypoxic group was exposed to lower levels of hypobaric hypoxia during our mountaineering expedition to Mt Everest. The oxygen level was decreased according to our climbing protocol from 21% to about 7% over a period of 15 days. Food and water were changed daily during the course of the experiment. After 15 days animals were euthanized after whole blood extraction from V. Cava for further analysis. RNA from whole blood was isolated, processed and used for microarray-based expression profiling. Profiles were generated for genes differentially expressed at control versus hypobaric hypoxia in whole blood using a false discovery rate (FDR) of 0%.We validated the profiles by real-time quantitative reverse transcription-polymerase chain reaction (qPCR). Results: The regional transcriptomes associated with hypobaric hypoxia on Mt. Everest in whole blood were identified. We found 947 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 between control and hypobaric hypoxia in whole blood. Our definition of the synaptic transcriptome provides insight into the functioning of the unique response to hypoxia in whole blood.
2010-05-07 | E-GEOD-15901 | biostudies-arrayexpress
Project description:Purpose: Bulk RNA-Seq of wild-type mice retina after different hypoxic exposures, to evaluate the influence on retinal pathologies. Methods: Retinal mRNA profiles of C57BL/6J mice after 6 different hypoxic exposures were generated by deep sequencing (n=6) using paired-end high output sequencing (Illumina Novaseq 6000). Results: Longitudinal studies over 11 weeks in normobaric hypoxia revealed four classes of genes that adapted differentially to the long-term hypoxic condition. Many differentially expressed genes were involved in the regulation of gene expression. Seventeen genes were specifically regulated in hypobaric hypoxia. Some of these genes may affect the structural integrity of the retina or individual cells, resulting in the slight shortening of photoreceptor segment length detected in various hypoxic groups.
2021-08-10 | GSE173233 | GEO
Project description:Background: Constant hypoxia (CH) and intermittent hypoxia (IH) occur during several pathological conditions such as asthma and obstructive sleep apnea. Our research is focused on understanding the molecular mechanisms that lead to injury or adaptation to hypoxic stress using Drosophila as a model system. Our current genome-wide study is designed to investigate gene expression changes and identify protective mechanism(s) in D. melanogaster after exposure to severe (1% O2) intermittent or constant hypoxia. Methodology/Principal Findings: Our microarray analysis has identified multiple gene families that are up- or down-regulated in response to acute CH or IH. We observed distinct responses to IH and CH in gene expression that varied in the number of genes and type of gene families. We then studied the role of candidate genes (up-or down-regulated) in hypoxia tolerance (adult survival) for longer periods (CH-7 days, IH-10 days) under severe CH or IH. Heat shock proteins up-regulation (specifically Hsp23 and Hsp70) led to a significant increase in adult survival (as compared to controls) of P-element lines during CH. In contrast, during IH treatment the up-regulation of Mdr49 and l(2)08717 genes (P-element lines) provided survival advantage over controls. This suggests that the increased transcript levels following treatment with either paradigm play an important role in tolerance to severe hypoxia. Furthermore, by over-expressing Hsp70 in specific tissues, we found that up-regulation of Hsp70 in heart and brain play critical role in tolerance to CH in flies. Conclusions/Significance: We observed that the gene expression response to IH or CH is specific and paradigm-dependent. We have identified several genes Hsp23, Hsp70, CG1600, l(2)08717 and Mdr49 that play an important role in hypoxia tolerance whether it is in CH or IH. These data provide further clues about the mechanisms by which IH or CH lead to cell injury and morbidity or adaptation and survival. Expression profiles were determined by expression arrays in Drosophila melanogaster following acute constant or intermittent hypoxia. Three groups of samples were included in this analysis (3 x control, 3x CH treated and 3 x IH treated samples).
2009-04-30 | E-GEOD-14981 | biostudies-arrayexpress
Project description:To address whether hypoxia contributes to muscle patho-physiology, normal, adult C57 mice were exposed to chronic, normobaric and hypobaric hypoxic environments for 2 weeks in order to simulate levels of hypoxaemia reported in DMD patients with advanced respiratory insufficiency. Control mice were maintained under normoxic conditions. Control and experimental mice were studied. Keywords: Hypoxia effect, Comparison type
2009-10-10 | GSE9400 | GEO
Project description:Tibetan chickens, a unique plateau breed, have good performances to adapt to high-altitude hypoxic environments. A number of positively selected genes have been reported in Tibetan chickens; however, the mechanisms of gene expression for hypoxia adaptation are not fully understood. In the present study, eggs from Tibetan (TC) and Chahua (CH) chickens were incubated under hypoxic and normoxic conditions, and vascularization in the chorioallantoic membrane (CAM) of embryos was observed. We found that the vessel density index (VDI) in CAM of TCs was lower than in CHs under hypoxia incubation.Proteomic analyses of CAM tissues were performed in TC and CH embryos under hypoxic incubation using iTRAQ. We obtained 387 differentially expressed proteins (DEPs) that were mainly enriched in angiogenesis, vasculature development, blood vessel morphogenesis, blood circulation, renin-angiotensin system, and HIF-1 and VEGF signaling pathways. Twenty-six genes involved in angiogenesis and blood circulation, two genes involved in ion transport, and six genes that regulated energy metabolism were identified as candidate functional genes in regulating hypoxic adaption of chicken embryos. Therefore, this research provided insights into the molecular mechanism of hypoxia adaptation in Tibetan chickens.
2021-09-08 | PXD012607 | Pride
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).
2010-04-25 | GSE15894 | GEO
Project description:Background: Constant hypoxia (CH) and intermittent hypoxia (IH) occur during several pathological conditions such as asthma and obstructive sleep apnea. Our research is focused on understanding the molecular mechanisms that lead to injury or adaptation to hypoxic stress using Drosophila as a model system. Our current genome-wide study is designed to investigate gene expression changes and identify protective mechanism(s) in D. melanogaster after exposure to severe (1% O2) intermittent or constant hypoxia. Methodology/Principal Findings: Our microarray analysis has identified multiple gene families that are up- or down-regulated in response to acute CH or IH. We observed distinct responses to IH and CH in gene expression that varied in the number of genes and type of gene families. We then studied the role of candidate genes (up-or down-regulated) in hypoxia tolerance (adult survival) for longer periods (CH-7 days, IH-10 days) under severe CH or IH. Heat shock proteins up-regulation (specifically Hsp23 and Hsp70) led to a significant increase in adult survival (as compared to controls) of P-element lines during CH. In contrast, during IH treatment the up-regulation of Mdr49 and l(2)08717 genes (P-element lines) provided survival advantage over controls. This suggests that the increased transcript levels following treatment with either paradigm play an important role in tolerance to severe hypoxia. Furthermore, by over-expressing Hsp70 in specific tissues, we found that up-regulation of Hsp70 in heart and brain play critical role in tolerance to CH in flies. Conclusions/Significance: We observed that the gene expression response to IH or CH is specific and paradigm-dependent. We have identified several genes Hsp23, Hsp70, CG1600, l(2)08717 and Mdr49 that play an important role in hypoxia tolerance whether it is in CH or IH. These data provide further clues about the mechanisms by which IH or CH lead to cell injury and morbidity or adaptation and survival.
2009-04-30 | GSE14981 | GEO
Project description:In order to study the gene expression profile in C57Bl/10 mouse blood, we exposed three different groups of animals. First was exposed to PO2 21% or normoxia. The second was exposed to chronic hypoxia (from PO2 21% to PO2 8%) and the third was also exposed to the same chronic hypoxia (CH) protocol but followed by two weeks under normoxia, and called as recovery group. The blood was extracted from inferior vena cava, the RNA was extracted, amplified and hybridized to Affimetrix MOE 430 V2.o chip. The results were analyzed using Partek Genome suite software. Using two fold cuttoff and 0% FDR parameters, we observed genes 512 diferentially expressed, of which one gene was up-regulated in both hypoxic and recovery condition, 202 were up-regulated during CH and then down-regulated after the recovery, 18 genes were down-regulated afteh CH and the up-regulated after recovery, ans finally 9 genes were down-regulated in both CH and recovery conditions. Each group of C57Bl/10 mouse had 4 individuals and they were divided into three different groups of animals. First was exposed to PO2 21% or normoxia for 14 days. The second was exposed to chronic hypoxia (from PO2 21% to PO2 8%) and the third was also exposed to the same chronic hypoxia (CH) protocol but followed by two weeks under normoxia, and called as recovery group. After the exposure period, the animals were anaesthetized with a mix of Ketamine (100 mg/mL) and xylasine (20 mg/mL) in a proportion of 1:1. A incison was made on abdominal area and from kidneis and liver area of inferior vena cava venus blood was collected The blood was extracted from inferior vena cava. Then, the RNA was extracted, amplified and hybridized to Affimetrix MOE 430 V2.o chip. The results were analyzed using Partek Genome suite software. Using two fold cuttoff and 0% FDR parameters, we observed genes 512 diferentially expressed, of which one gene was up-regulated in both hypoxic and recovery condition, 202 were up-regulated during CH and then down-regulated after the recovery, 18 genes were down-regulated afteh CH and the up-regulated after recovery, ans finally 9 genes were down-regulated in both CH and recovery conditions.
2012-05-25 | E-GEOD-17728 | biostudies-arrayexpress