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Combined targeted and non-targeted metabolomics-based approaches for analyzing the profile of oxylipins in the ATP-stimulated astrocytesстатья Тезисы
- Авторы: Gorbatenko V., Drozhdev A., Goriainov S., Sergeeva M.G., Chistyakov D.V.
- Сборник: FEBS OPEN BIO 2024
- Том: 14
- Год издания: 2024
- Место издания: Wiley
- Первая страница: 119
- Последняя страница: 119
- Номер статьи: P-03-029
- DOI: 10.1002/2211-5463.13837
- Аннотация: Over the last decade, we observed a significant breakthrough in the understanding molecular mechanisms of neuropathological processes. It largely arose from studying numerous metabolites by the targeted and non-targeted (metabolic fingerprinting) metabolomics-based approaches. The ATP-dependent activation of the astrocyte P2-purinergic receptors is crucial for inflammation and the development of neuropathologies. Oxylipins, the oxidized derivatives of polyunsaturated fatty acids (PUFAs), mediate inflammatory processes. However, the profile of oxylipins upon the ATP-induced cell activation has not been analyzed yet. Employing the non-targeted (GC/MS) and targeted (UPLCMS/MS) metabolomics-based approaches, we obtained the oxylipin profiles after the 15-min stimulation with 100 lM ATP (the acute response) and evaluated the ability of metformin, considered as a potential anti-inflammatory drug for treating CNS pathologies, to alter the profile of oxylipins. We assessed 50 compounds involved in the enzymatic pathways of oxylipin biosynthesis dependent on the lipoxygenase (LOX), cyclooxygenase (COX), and epoxygenase (CYP). ATP induced a significant activation of the COX pathway reflected by elevated levels of TXB2, PGD2, 12-HHT, but not of PGE2, indicating the activation of the thromboxane synthase and PGD synthase upon P2 receptor stimulation. Treating cells with metformin prior to the stimulation with ATP had no effect on TXB2 and PGD2, whereas it promoted the synthesis of 12-HHT and 11-HETE metabolites. In contrast to the derivatives of arachidonic acid, the profile of oxylipins, the metabolites of other PUFAs, was not altered. The ability of metformin to induce the synthesis of 12-HHT,an endogenous ligand of the BLT2 receptor, reveals novel mechanisms underlying its anti-inflammatory activity, although the biological role of 12-HHT in the CNS is yet to be clarified. This work was supported by the RUDN University Scientific Projects Grant System №214853-2-000. *The authors marked with an asterisk equally contributed to the work.
- Добавил в систему: Чистяков Дмитрий Викторович