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Article

Metabolomic Profiling of Plasma and Erythrocytes in Sickle Mice Points to Altered Nociceptive Pathways

1
Faculté de Pharmacie, Université des Sciences, des Techniques et des Technologies de Bamako BP, Bamako 1805, Mali
2
Département de Biochimie et Génétique, Centre Hospitalier Universitaire, 49933 Angers, France
3
Unité Mixte de Recherche (UMR) MITOVASC, Centre National de la Recherche Scientifique (CNRS) 6015, Institut National de la Santé et de la Recherche Médicale (INSERM) U1083, Université d’Angers, 49933 Angers, France
4
Paris Cardiovascular Centre (PARCC), Institut National de la Santé et de la Recherche Médicale (INSERM), 75015 Paris, France
5
Institut National de la Santé et de la Recherche Médicale (INSERM) U1253, Université François Rabelais de Tours, 37000 Tours, France
6
Laboratoire de Biochimie et Biologie Moléculaire, Centre Hospitalier Universitaire de Tours, 37000 Tours, France
7
Université Paris Descartes, Sorbonne Paris Cité, 75006 Paris, France
8
Nephrology Division, Georges Pompidou European Hospital, Assistance Publique-Hôpitaux de Paris, 75015 Paris, France
*
Authors to whom correspondence should be addressed.
These authors contributed equally to this work.
Cells 2020, 9(6), 1334; https://doi.org/10.3390/cells9061334
Received: 7 May 2020 / Revised: 21 May 2020 / Accepted: 23 May 2020 / Published: 26 May 2020
(This article belongs to the Special Issue Metabolomics in Physiology and Diseases)
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. View Full-Text
Keywords: metabolomics; lipidomics; nociception; sickle cell disease metabolomics; lipidomics; nociception; sickle cell disease
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MDPI and ACS Style

Dembélé, K.C.; Mintz, T.; Veyrat-Durebex, C.; Chabrun, F.; Chupin, S.; Tessier, L.; Simard, G.; Henrion, D.; Mirebeau-Prunier, D.; Chao de la Barca, J.M.; Tharaux, P.-L.; Reynier, P. Metabolomic Profiling of Plasma and Erythrocytes in Sickle Mice Points to Altered Nociceptive Pathways. Cells 2020, 9, 1334. https://doi.org/10.3390/cells9061334

AMA Style

Dembélé KC, Mintz T, Veyrat-Durebex C, Chabrun F, Chupin S, Tessier L, Simard G, Henrion D, Mirebeau-Prunier D, Chao de la Barca JM, Tharaux P-L, Reynier P. Metabolomic Profiling of Plasma and Erythrocytes in Sickle Mice Points to Altered Nociceptive Pathways. Cells. 2020; 9(6):1334. https://doi.org/10.3390/cells9061334

Chicago/Turabian Style

Dembélé, Klétigui C., Thomas Mintz, Charlotte Veyrat-Durebex, Floris Chabrun, Stéphanie Chupin, Lydie Tessier, Gilles Simard, Daniel Henrion, Delphine Mirebeau-Prunier, Juan M. Chao de la Barca, Pierre-Louis Tharaux, and Pascal Reynier. 2020. "Metabolomic Profiling of Plasma and Erythrocytes in Sickle Mice Points to Altered Nociceptive Pathways" Cells 9, no. 6: 1334. https://doi.org/10.3390/cells9061334

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