Dataset Information

Alterations of human plasma proteome profile on adaptation to high-altitude hypobaric hypoxia

ABSTRACT: For individuals migrating to or residing permanently at high-altitude regions, environmental hypobaric hypoxia is a primary challenge which induces several physiological or pathological responses. It is well documented that human beings adapt to hypobaric hypoxia via some protective mechanisms, such as erythropoiesis and overproduction of hemoglobin, however little is known on the changes of plasma proteome profiles in accommodation to high-altitude hypobaric hypoxia. In the present study, we investigated differential plasma proteomes of high altitude natives and lowland normal controls by a TMT-based proteomic approach. A total of 818 proteins were identified, of which 137 were differentially altered. Bioinformatics (including GO, KEGG, protein-protein interactions, etc.) analysis revealed the dysregulated proteins were primarily involved in complement and coagulation cascades, anti-oxidative stress and glycolysis. Validations via magnetic Luminex® Assays and ELISA demonstrated that CCL18, C9, PF4, MPO and S100A9 notably up-regulated, and HRG and F11 down-regulated in high altitude natives compared with lowland controls, which were consistent with the proteomic results. Our findings highlight the roles of complement and coagulation cascades, anti-oxidative stress and glycolysis in acclimatization to hypobaric hypoxia and provide a foundation for developing potential diagnostic or/and therapeutic biomarkers for high altitude hypobaric hypoxia-induced diseases.

INSTRUMENT(S): Q Exactive Plus

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Blood Plasma

SUBMITTER: xiaonan fu

LAB HEAD: Zongkui Wang

PROVIDER: PXD012221 | Pride | 2019-03-27

REPOSITORIES: Pride

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Alterations of Human Plasma Proteome Profile on Adaptation to High-Altitude Hypobaric Hypoxia.

Du Xi X Zhang Rong R Ye Shengliang S Liu Fengjuan F Jiang Peng P Yu Xiaochuan X Xu Jin J Ma Li L Cao Haijun H Shen Yuanzhen Y Lin Fangzhao F Wang Zongkui Z Li Changqing C

Journal of proteome research 20190403 5

For individuals migrating to or residing permanently in high-altitude regions, environmental hypobaric hypoxia is a primary challenge that induces several physiological or pathological responses. It is well documented that human beings adapt to hypobaric hypoxia via some protective mechanisms, such as erythropoiesis and overproduction of hemoglobin; however, little is known on the alterations of plasma proteome profiles in accommodation to high-altitude hypobaric hypoxia. In the present study, w ...[more]

PMID: 30908922

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Project description:Background: Responses to hypoxia have been investigated in many species; however, comparative study between conspecific geographical populations in different altitude regions is rare, especially for invertebrates . The migratory locust, Locusta migratoria, is widely distributed both on high-altitude Tibetan Plateau (TP) and on low-altitude North China Plain (NP). TP locusts have inhabited Tibetan Plateau since Quaternary glaciations events and thus probably have evolved superior capacity to deal with hypoxia. Results: Here we compared the hypoxic responses of TP and NP locusts from morphological, behavioral and physiological perspectives. We found that TP locusts were more tolerant of extreme hypoxia than NP locusts, with a lower proportion exhibiting stupor, a faster recovery time, and higher respiration rates. We compared the transcriptional profiles of field TP and NP locusts and found that their differences were possibly attributed to a combination of multiple factors, e.g. oxygen, UV radiation, temperature and nutrition. To evaluate why TP locusts respond to extreme hypoxia differently from NP locusts, we subjected them to extreme hypoxia and compared their transcriptional responses. We found that the aerobic metabolism was more active in TP locusts than in NP locusts. RNAi disruption of PDHE1b, an entry gene from glycolysis to TCA cycle, increased the ratio of stupor in Tibetan locusts and decreased the ATP content of Tibetan locusts in hypoxia, confirming the significant importance of this metabolic branch for TP locusts to conquer hypoxia. Conclusions: Here we show that TP locusts are better tolerant of hypoxia than NP locusts and the better capacity to modulate primary metabolism in TP locusts contributes to their superior tolerance of hypoxia compared to NP locusts. FIELD POPULATION: TP locusts vs. NP locusts;direct comparison on 6 separate microarrays; each microarray compares one biological replicate; each biological replicate contains 10 individuals. LAB POPULATION: hypoxia-treated TP locusts vs TP locusts in normoxia; hypoxia-treated NP locusts vs NP locusts in normoxia; direct comparison on 6 separate microarrays; each microarray compares one biological replicate; each biological replicate contains 10 individuals.

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¬Æ 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¬Æ profiling was performed for individual flies from each experimental group. 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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¬Æ 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). 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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%)

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