1. Vladivostok Branch of the Far Eastern Scientific Center for Physiology and Pathology of Respiration - Research Institute of Medical Climatology and Rehabilitation Treatment, Vladivostok, Russia 2. A.V. Zhirmunsky National Scientific Center for Marine Biology, Far Eastern Branch of the Russian Academy of Sciences, Vladivostok, Russia
Bronchial asthma (BA) complicated by obesity is a progressive disease phenotype that hardly responds to standard therapy. In this regard, it is important to elucidate cellular and molecular mechanisms of development of this comorbid pathology. In recent years, lipidomics has become an active research tool, opening new opportunities not only for understanding cellular processes in health and disease, but also for providing a personalized approach to medicine. The aim of this study was to characterize the lipidome phenotype based on the study of molecular species of glycerophosphatidylethanolamines (GPEs) in blood plasma of patients with BA complicated by obesity. Molecular species of GPEs were studied in blood samples of 11 patients. Identification and quantification of GPEs was carried out using high resolution tandem mass spectrometry. For the first time in this pathology, a change in the lipidome profile of molecular species of diacyl, alkyl-acyl and alkenyl-acyl HPEs of blood plasma was shown. In BA complicated by obesity, acyl groups 18:2 and 20:4 were dominated in the sn2 position of the molecular composition of diacylphosphoethanolamines. Simultaneously with the increase in the level of GPE diacyls with the fatty acids (FA) 20:4, 22:4, and 18:2, there was a decrease in these FAs in alkyl and alkenyl molecular species of GPEs, thus indicating their redistribution between subclasses. The eicosapentaenoic acid (20:5) deficiency at the sn2 position of alkenyl GPEs in patients with BA complicated by obesity indicates a decrease in the substrate for the synthesis of anti-inflammatory mediators. The resulting imbalance in the distribution of GPE subclasses, due to a pronounced increase in the content of diacyl GPE under conditions of the deficiency of molecular species of ether forms, can probably cause chronic inflammation and the development of oxidative stress. The recognized lipidome profile characterized by the modification of the basic composition and the chemical structure of GPE molecular species in BA complicated by obesity indicates their involvement in the pathogenetic mechanisms underlying BA development. The elucidation of particular roles of individual subclasses of glycerophospholipids and their individual members may contribute to the identification of new therapeutic targets and biomarkers of bronchopulmonary pathology.
Denisenko Yu.K., Omatova U.M., Novgorodtseva T.P., Ermolenko E.V. (2023) Molecular species of glycerophosphoethanolamines in obesity-associated asthma. Biomeditsinskaya Khimiya, 69(3), 174-183.
Denisenko Yu.K. et al. Molecular species of glycerophosphoethanolamines in obesity-associated asthma // Biomeditsinskaya Khimiya. - 2023. - V. 69. -N 3. - P. 174-183.
Denisenko Yu.K. et al., "Molecular species of glycerophosphoethanolamines in obesity-associated asthma." Biomeditsinskaya Khimiya 69.3 (2023): 174-183.
Denisenko, Yu. K., Omatova, U. M., Novgorodtseva, T. P., Ermolenko, E. V. (2023). Molecular species of glycerophosphoethanolamines in obesity-associated asthma. Biomeditsinskaya Khimiya, 69(3), 174-183.
References
Nelson D.L., Cox M.M. (2008) Lehninger Principles of Biochemistry. 5th Edition, W.H. Freeman Macmillan, New York. Scholar google search
Denisenko Y.K., Kytikova O.Y., Novgorodtseva T.P., Antonyuk M.V., Gvozdenko T.A., Kantur T.A. (2020) Lipid-induced mechanisms of metabolic syndrome. J. Obesity, 2020, 5762395. CrossRef Scholar google search
Liebisch G., Fahy E., Aoki J., Dennis E.A., Durand T., Ejsing C.S., Fedorova M., Feussner I., Griffiths W.J., Köfeler H., Merrill A.H. Jr, Murphy R.C., O'Donnell V.B., Oskolkova O., Subramaniam S., Wakelam M.J.O., Spener F. (2020) Update on LIPID MAPS classification, nomenclature, and shorthand notation for MS-derived lipid structures. J. Lipid Res., 61(12), 1539-1555. CrossRef Scholar google search
Farine L., Niemann M., Schneider A., Bütikofer P. (2015) Phosphatidylethanolamine and phosphatidylcholine biosynthesis by the Kennedy pathway occurs at different sites in Trypanosoma brucei. Sci. Rep., 5(1), 16787. CrossRef Scholar google search
Patel D., Witt S.N. (2017) Ethanolamine and phosphatidylethanolamine: Partners in health and disease. Oxid. Med. Cell. Longev., 2017, 4829180. CrossRef Scholar google search
Calzada E., Onguka O., Claypool S.M. (2016) Phosphatidylethanolamine metabolism in health and disease. Int. Rev. Cell Mol. Biol., 321, 29-88. CrossRef Scholar google search
Kytikova O., Novgorodtseva T., Denisenko Y., Antonyuk M., Gvozdenko T. (2019) Pro-resolving lipid mediators in the pathophysiology of asthma. Medicina (Kaunas, Lithuania), 55(6), 284. CrossRef Scholar google search
Hatton S.L., Pandey M.K. (2022) Fat and protein combat triggers immunological weapons of innate and adaptive immune systems to launch neuroinflammation in Parkinson's disease. Int. J. Mol. Sci., 23(3), 1089. CrossRef Scholar google search
Valentine W.J., Hashidate-Yoshida T., Yamamoto S., Shindou H. (2020) Biosynthetic enzymes of membrane glycerophospholipid diversity as therapeutic targets for drug development. Adv. Exp. Med. Biol, 1274, 5-27. CrossRef Scholar google search
Bligh E.G., Dyer W.J. (1959) A rapid method of total lipid extraction and purification. Can. J. Biochem. Physiol., 37(8), 911-917. CrossRef Scholar google search
Carreau J.P., Dubacq J.P. (1978) Adaptation of a macro-scale method to the micro-scale for fatty acid methyl transesterification of biological lipid extracts. J. Chromatography A, 151(3), 384-390. CrossRef Scholar google search
Christie W.W. (1988) Equivalent chain-lengths of methyl ester derivatives of fatty acids on gas chromatography: A reappraisal. J. Chromatography A, 447, 305-314. CrossRef Scholar google search
Imbs A.B., Dang L.P., Rybin V.G., Svetashev V.I. (2015) Fatty acid, lipid class, and phospholipid molecular species composition of the soft coral Xenia sp.(Nha Trang Bay, the South China Sea, Vietnam). Lipids, 50, 575-589. CrossRef Scholar google search
Panda L., Gheware A., Rehman R., Yadav M.K., Jayaraj B.S., Madhunapantula S.V., Mahesh P.A., Ghosh B., Agrawal A., Mabalirajan U. (2017) Linoleic acid metabolite leads to steroid resistant asthma features partially through NF-κB. Sci. Rep., 7(1), 9565. CrossRef Scholar google search
Almsherqi Z.A. (2021) Potential role of plasmalogens in the modulation of biomembrane morphology. Front. Cell Dev. Biol., 9, 673917. CrossRef Scholar google search
Astudillo A.M., Balboa M.A., Balsinde J. (2022) Compartmentalized regulation of lipid signaling in oxidative stress and inflammation: Plasmalogens, oxidized lipids and ferroptosis as new paradigms of bioactive lipid research Prog. Lipid. Res , 89, 101207. CrossRef Scholar google search
Gibellini F., Smith T.K. (2010) The Kennedy pathway — de novo synthesis of phosphatidylethanolamine and phosphatidylcholine. IUBMB Life, 62(6), 414-428. CrossRef Scholar google search
O'Donnell V.B. (2022) New appreciation for an old pathway: The Lands cycle moves into new arenas in health and disease. Biochem. Soc. Trans., 50(1), 1-11. CrossRef Scholar google search
Moessinger C., Klizaite K., Steinhagen A., Philippou-Massier J., Shevchenko A., Hoch M., Ejsing C.S., Thiele C. (2014) Two different pathways of phosphatidylcholine synthesis, the Kennedy Pathway and the Lands Cycle, differentially regulate cellular triacylglycerol storage. BMC Cell Biology, 15(1), 1-17. CrossRef Scholar google search
Annibal A., Riemer T., Jovanovic O., Westphal D., Griesser E., Pohl E.E., Schiller J., Hoffmann R., Fedorova M. (2016) Structural, biological and biophysical properties of glycated and glycoxidized phosphatidylethanolamines. Free Rad. Biol. Med., 95, 293-307. CrossRef Scholar google search
Basu Ball W., Neff J.K., Gohil V.M. (2018) The role of nonbilayer phospholipids in mitochondrial structure and function. FEBS Lett., 592(8), 1273-1290. CrossRef Scholar google search
Denisenko Yu.K., Bocharova N.V., Kovalenko I.S., Novgorodtseva T.P. (2022) Influence of N-acyl-ethanolamine of arachidonic acid on the synthesis of cytokines and oxylipins by the blood leukocytes of patients with asthma under in vitro conditions. Bulletin of Physiology and Pathology of Respiration, 83, 15-21. CrossRef Scholar google search
Dawaliby R., Trubbia C., Delporte C., Noyon C., Ruysschaert J.M., van Antwerpen P., Govaerts C. (2016) Phosphatidylethanolamine is a key regulator of membrane fluidity in eukaryotic cells. J. Biol. Chem., 291(7), 3658-3667. CrossRef Scholar google search
