{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,18]],"date-time":"2026-10-18T03:13:49Z","timestamp":1792293229650,"version":"4.4.0"},"reference-count":41,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2020,5,26]],"date-time":"2020-05-26T00:00:00Z","timestamp":1590451200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Few data-driven metabolomic approaches have been reported in sickle cell disease (SCD) to date. We performed a metabo-lipidomic study on the plasma and red blood cells of a steady-state mouse model carrying the homozygous human hemoglobin SS, compared with AS and AA genotypes. Among the 188 metabolites analyzed by a targeted quantitative metabolomic approach, 153 and 129 metabolites were accurately measured in the plasma and red blood cells, respectively. Unsupervised PCAs (principal component analyses) gave good spontaneous discrimination between HbSS and controls, and supervised OPLS-DAs (orthogonal partial least squares-discriminant analyses) provided highly discriminant models. These models confirmed the well-known deregulation of nitric oxide synthesis in the HbSS genotype, involving arginine deficiency and increased levels of dimethylarginines, ornithine, and polyamines. Other discriminant metabolites were newly evidenced, such as hexoses, alpha-aminoadipate, serotonin, kynurenine, and amino acids, pointing to a glycolytic shift and to the alteration of metabolites known to be involved in nociceptive pathways. Sharp remodeling of lysophosphatidylcholines, phosphatidylcholines, and sphingomyelins was evidenced in red blood cells. Our metabolomic study provides an overview of the metabolic remodeling induced by the sickle genotype in the plasma and red blood cells, revealing a biological fingerprint of altered nitric oxide, bioenergetics and nociceptive pathways.<\/jats:p>","DOI":"10.3390\/cells9061334","type":"journal-article","created":{"date-parts":[[2020,5,29]],"date-time":"2020-05-29T00:44:02Z","timestamp":1590713042000},"page":"1334","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Metabolomic Profiling of Plasma and Erythrocytes in Sickle Mice Points to Altered Nociceptive Pathways"],"prefix":"10.3390","volume":"9","author":[{"given":"Kl\u00e9tigui Casimir","family":"Demb\u00e9l\u00e9","sequence":"first","affiliation":[{"name":"Facult\u00e9 de Pharmacie, Universit\u00e9 des Sciences, des Techniques et des Technologies de Bamako BP, Bamako 1805, Mali"},{"name":"D\u00e9partement de Biochimie et G\u00e9n\u00e9tique, Centre Hospitalier Universitaire, 49933 Angers, France"},{"name":"Unit\u00e9 Mixte de Recherche (UMR) MITOVASC, Centre National de la Recherche Scientifique (CNRS) 6015, Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale (INSERM) U1083, Universit\u00e9 d\u2019Angers, 49933 Angers, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Mintz","sequence":"additional","affiliation":[{"name":"Paris Cardiovascular Centre (PARCC), Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale (INSERM), 75015 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4512-2303","authenticated-orcid":false,"given":"Charlotte","family":"Veyrat-Durebex","sequence":"additional","affiliation":[{"name":"Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale (INSERM) U1253, Universit\u00e9 Fran\u00e7ois Rabelais de Tours, 37000 Tours, France"},{"name":"Laboratoire de Biochimie et Biologie Mol\u00e9culaire, Centre Hospitalier Universitaire de Tours, 37000 Tours, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6871-8711","authenticated-orcid":false,"given":"Floris","family":"Chabrun","sequence":"additional","affiliation":[{"name":"D\u00e9partement de Biochimie et G\u00e9n\u00e9tique, Centre Hospitalier Universitaire, 49933 Angers, France"},{"name":"Unit\u00e9 Mixte de Recherche (UMR) MITOVASC, Centre National de la Recherche Scientifique (CNRS) 6015, Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale (INSERM) U1083, Universit\u00e9 d\u2019Angers, 49933 Angers, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"St\u00e9phanie","family":"Chupin","sequence":"additional","affiliation":[{"name":"D\u00e9partement de Biochimie et G\u00e9n\u00e9tique, Centre Hospitalier Universitaire, 49933 Angers, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lydie","family":"Tessier","sequence":"additional","affiliation":[{"name":"D\u00e9partement de Biochimie et G\u00e9n\u00e9tique, Centre Hospitalier Universitaire, 49933 Angers, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gilles","family":"Simard","sequence":"additional","affiliation":[{"name":"D\u00e9partement de Biochimie et G\u00e9n\u00e9tique, Centre Hospitalier Universitaire, 49933 Angers, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1094-0285","authenticated-orcid":false,"given":"Daniel","family":"Henrion","sequence":"additional","affiliation":[{"name":"Unit\u00e9 Mixte de Recherche (UMR) MITOVASC, Centre National de la Recherche Scientifique (CNRS) 6015, Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale (INSERM) U1083, Universit\u00e9 d\u2019Angers, 49933 Angers, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Delphine","family":"Mirebeau-Prunier","sequence":"additional","affiliation":[{"name":"D\u00e9partement de Biochimie et G\u00e9n\u00e9tique, Centre Hospitalier Universitaire, 49933 Angers, France"},{"name":"Unit\u00e9 Mixte de Recherche (UMR) MITOVASC, Centre National de la Recherche Scientifique (CNRS) 6015, Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale (INSERM) U1083, Universit\u00e9 d\u2019Angers, 49933 Angers, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan Manuel","family":"Chao de la Barca","sequence":"additional","affiliation":[{"name":"D\u00e9partement de Biochimie et G\u00e9n\u00e9tique, Centre Hospitalier Universitaire, 49933 Angers, France"},{"name":"Unit\u00e9 Mixte de Recherche (UMR) MITOVASC, Centre National de la Recherche Scientifique (CNRS) 6015, Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale (INSERM) U1083, Universit\u00e9 d\u2019Angers, 49933 Angers, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6062-5905","authenticated-orcid":false,"given":"Pierre-Louis","family":"Tharaux","sequence":"additional","affiliation":[{"name":"Paris Cardiovascular Centre (PARCC), Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale (INSERM), 75015 Paris, France"},{"name":"Universit\u00e9 Paris Descartes, Sorbonne Paris Cit\u00e9, 75006 Paris, France"},{"name":"Nephrology Division, Georges Pompidou European Hospital, Assistance Publique-H\u00f4pitaux de Paris, 75015 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0802-4608","authenticated-orcid":false,"given":"Pascal","family":"Reynier","sequence":"additional","affiliation":[{"name":"D\u00e9partement de Biochimie et G\u00e9n\u00e9tique, Centre Hospitalier Universitaire, 49933 Angers, France"},{"name":"Unit\u00e9 Mixte de Recherche (UMR) MITOVASC, Centre National de la Recherche Scientifique (CNRS) 6015, Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale (INSERM) U1083, Universit\u00e9 d\u2019Angers, 49933 Angers, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,5,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"326","DOI":"10.1038\/180326a0","article-title":"Gene mutations in human haemoglobin: The chemical difference between normal and sickle cell haemoglobin","volume":"180","author":"Ingram","year":"1957","journal-title":"Nature"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"772","DOI":"10.1177\/1535370216640150","article-title":"Minireview: Multiomic candidate biomarkers for clinical manifestations of sickle cell severity: Early steps to precision medicine","volume":"241","author":"Goodman","year":"2016","journal-title":"Exp. 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