Plasmalogen oxidation induces the generation of excited molecules and electrophilic lipid species

Autor(es)

Faria, Rodrigo L. ; Prado, Fernanda M. ; Junqueira, Helena C. ; Fabiano, Karen C. ; Diniz, Larissa R. ; Baptista, Mauricio S. ; Di Mascio, Paolo ; Miyamoto, Sayuri

• Tipo de documento: Artigo Científico
• Fonte: PNAS NEXUS; v. 3, n. 6, p. 12-pg., 2024-06-18.

Resumo

Plasmalogens are glycerophospholipids with a vinyl ether linkage at the sn-1 position of the glycerol backbone. Despite being suggested as antioxidants due to the high reactivity of their vinyl ether groups with reactive oxygen species, our study reveals the generation of subsequent reactive oxygen and electrophilic lipid species from oxidized plasmalogen intermediates. By conducting a comprehensive analysis of the oxidation products by liquid chromatography coupled to high-resolution mass spectrometry (LC-HRMS), we demonstrate that singlet molecular oxygen [O2 (1 Delta g)] reacts with the vinyl ether bond, producing hydroperoxyacetal as a major primary product (97%) together with minor quantities of dioxetane (3%). Furthermore, we show that these primary oxidized intermediates are capable of further generating reactive species including excited triplet carbonyls and O2 (1 Delta g) as well as electrophilic phospholipid and fatty aldehyde species as secondary reaction products. The generation of excited triplet carbonyls from dioxetane thermal decomposition was confirmed by light emission measurements in the visible region using dibromoanthracene as a triplet enhancer. Moreover, O2 (1 Delta g) generation from dioxetane and hydroperoxyacetal was evidenced by detection of near-infrared light emission at 1,270 nm and chemical trapping experiments. Additionally, we have thoroughly characterized alpha-beta unsaturated phospholipid and fatty aldehydes by LC-HRMS analysis using two probes that specifically react with aldehydes and alpha-beta unsaturated carbonyls. Overall, our findings demonstrate the generation of excited molecules and electrophilic lipid species from oxidized plasmalogen species unveiling the potential prooxidant nature of plasmalogen-oxidized products. (AU)

• Processo FAPESP: 13/07937-8 - Redoxoma
• Beneficiário: Ohara Augusto
• Modalidade de apoio: Auxílio à Pesquisa - Centros de Pesquisa, Inovação e Difusão - CEPIDs
• Processo FAPESP: 17/16140-7 - Análises oxi-lipidômicas dos efeitos da oxidação dos plasmalogênios no remodelamento lipídico de células sob estresse oxidativo
• Beneficiário: Rodrigo Lucas de Faria
• Modalidade de apoio: Bolsas no Brasil - Doutorado Direto