Tag Archives: 2023

Keywords: COVID-19; Platelet lipidomics.

Phosphatidylinositols (PIs) are complex lipids that play a key role in cell signaling. Like other phospholipids, they are esterified with unsaturated fatty acyl residues (FAs), making them susceptible to modification by reactive oxygen and nitrogen species (RNS). Recent studies using mass spectrometry (MS)-based lipidomics approaches have revealed that lipid nitration results in a plethora of structurally and chemically modified lipids (epilipids), including nitrated and nitroxidized derivatives of phosphatidylcholines, phosphatidylethanolamines, phosphatidylserines, and cardiolipins. However, there is a notable lack of knowledge regarding the characterization of RNS-modified PI derivatives. In this study, we used C18 high-resolution liquid chromatography-tandem MS approaches to describe the fragmentation signature of nitrated and nitroxidized PIs, bearing different fatty acyl chains. Using this approach and accurate mass measurements, we were able to identify nitro- PI derivatives, dinitro- and nitrohydroxy- derivatives for a few PI species. The data showed the typical neutral loss of nitrous acid (HNO₂) as well as the fragmentation patterns corresponding to modified fatty acyl chains (such as NO_x-RCOO^–, [M – NO_x-RCOOH – H]^– and [M – NO_x-RCOOH – C₆H₁₀O₅ – H]^–), making it possible to identify these epilipids. The susceptibility of PIs to nitration was also investigated, revealing that it depends exclusively on the chains of unsaturated FAs esterified in PI, showing a higher conversion rate for those with C18:1. Overall, the knowledge gathered in this study will contribute to the precise characterization of these epilipids in complex biological samples, offering new opportunities to unveil the pathophysiological roles of nitrated and nitroxidized PI derivatives at the cellular and tissue levels.