{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T18:49:36Z","timestamp":1777661376708,"version":"3.51.4"},"reference-count":18,"publisher":"SAGE Publications","issue":"1","license":[{"start":{"date-parts":[[2023,3,1]],"date-time":"2023-03-01T00:00:00Z","timestamp":1677628800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2023,3,1]],"date-time":"2023-03-01T00:00:00Z","timestamp":1677628800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["High Altitude Medicine &amp; Biology"],"published-print":{"date-parts":[[2023,3,1]]},"abstract":"<jats:p>\n                    Xu, Jin, Shenhan Gao, Mingyuan Xin, Wenjie Chen, Kaikun Wang, Wenjing Liu, Xinzong Yan, Sinan Peng, and Yanming Ren. Comparative tandem mass tag-based quantitative proteomics analysis of liver against chronic hypoxia: molecular insights into metabolism in rats.\n                    <jats:italic toggle=\"yes\">High Alt Med Biol<\/jats:italic>\n                    . 24:49\u201358, 2023.\n                  <\/jats:p>\n                  <jats:sec>\n                    <jats:title>Objective:<\/jats:title>\n                    <jats:p>Using a metabolomic approach, we uncovered key regulators in metabolism from tandem mass tag (TMT)-based proteomic analysis in animals chronically exposed to hypoxia.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>\n                      Sixteen Sprague\u2013Dawley rats (\n                      <jats:italic toggle=\"yes\">n<\/jats:italic>\n                      \u2009=\u20098 per group) were exposed to chronic normoxia or hypoxia (380\u2009mmHg corresponding to a simulated altitude of 5,500\u2009m) for 35 consecutive days. Hypoxia-induced alterations in metabolic pathways were analyzed from TMT-based proteomic analysis, complemented by western blot validation of key regulators.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>\n                      We profiled biochemical parameters and serum lipids, found that serum alanine aminotransferase and blood glucose were not significantly changed due to chronic hypoxia. However, serum triglycerides, total cholesterol, high-density lipoprotein, and low-density lipoprotein (LDL) were significantly affected by chronic hypoxia. And the levels of LDL nearly doubled (\n                      <jats:italic toggle=\"yes\">p<\/jats:italic>\n                      \u2009&lt;\u20090.05) after hypoxia exposure for 35 days. Through Kyoto Encyclopedia of Genes and Genomes classification, we found several metabolic pathways were enriched, including lipid metabolism, cofactor and vitamin metabolism, amino acids metabolism, carbohydrate metabolism, and energy metabolism. To explore the potential functions of proteins in metabolic pathways that become a coordinated shift under chronic hypoxic conditions, Gene Ontology and pathway analysis were carried out on differentially expressed proteins. As the co-expression network shown in Figure, we identified the most significant differentially expressed proteins after chronic hypoxic changes in the livers of rats. Furthermore, we validated the gene expression profiles at the protein level using western blot. Results of western blot were in accordance with our quantitative polymerase chain reaction findings. The levels of fatty acid synthase and aquaporin 1 were significantly downregulated after 35 days and the levels of ATP citrate lyase, 2\u2032-5\u2032-oligoadenylate synthetase 1A, aldehyde dehydrogenase 2, and Ras-related protein Rap-1A were significantly upregulated after 35 days.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions:<\/jats:title>\n                    <jats:p>Although this study cannot completely account for all the molecular mechanisms in rats, we provide a good analysis of protein expression and profiling of rats under chronic hypoxia conditions.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1089\/ham.2022.0003","type":"journal-article","created":{"date-parts":[[2023,1,27]],"date-time":"2023-01-27T12:52:15Z","timestamp":1674823935000},"page":"49-58","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":1,"title":["Comparative Tandem Mass Tag-Based Quantitative Proteomics Analysis of Liver Against Chronic Hypoxia: Molecular Insights Into Metabolism in Rats"],"prefix":"10.1177","volume":"24","author":[{"given":"Jin","family":"Xu","sequence":"first","affiliation":[{"name":"Department of Medicine, Qinghai University, Xining, China."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shenhan","family":"Gao","sequence":"additional","affiliation":[{"name":"Department of Ecology, Qinghai University Plateau Biology Jing Ying Class, Grade 19, Xining, China."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mingyuan","family":"Xin","sequence":"additional","affiliation":[{"name":"Department of Medicine, Qinghai University Clinical Medicine Class 1, Grade 19, Xining, China."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wenjie","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Medicine, Qinghai University Clinical Medicine Class 6, Grade 20, Xining, China."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kaikun","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Medicine, Qinghai University Clinical Medicine Class 3, Grade 20, Xining, China."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wenjing","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Medicine, Qinghai University the Graduate Student of Foundation Medical of 2020, Xining, China."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xinzong","family":"Yan","sequence":"additional","affiliation":[{"name":"Department of Medicine, Qinghai University the Graduate Student of Foundation Medical of 2021, Xining, China."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sinan","family":"Peng","sequence":"additional","affiliation":[{"name":"Department of Mechanical Engineering, Qinghai University Material Forming and Control Engineering Class, Grade 20, Xining, China."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3796-5055","authenticated-orcid":false,"given":"Yanming","family":"Ren","sequence":"additional","affiliation":[{"name":"Department of Medicine, Qinghai University, Xining, China."}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"179","published-online":{"date-parts":[[2023,3,17]]},"reference":[{"issue":"1","key":"e_1_3_4_2_1","doi-asserted-by":"crossref","first-page":"1136","DOI":"10.1038\/s41598-020-58083-7","article-title":"Clonally selected primitive endothelial cells promote occlusive pulmonary arteriopathy and severe pulmonary hypertension in rats exposed to chronic hypoxia","volume":"10","author":"Bhagwani AR","year":"2020","unstructured":"Bhagwani AR, , Farkas D, , Harmon B, et al. 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