Untargeted Lipidomics of Erythrocytes under Simulated Microgravity Conditions

Abstract

Lipidomics and metabolomics are nowadays widely used to provide promising insights into the pathophysiology of cellular stress disorders. Our study expands, with the use of a hyphenated ion mobility mass spectrometric platform, the understanding of the cellular processes and stress due to microgravity. By lipid profiling of human erythrocytes, we annotated complex lipids such as oxidized phosphocholines, phosphocholines bearing arachidonic in their moiety, as well as sphingomyelins and hexosyl ceramides associated with microgravity conditions. Overall, our findings give an insight into the molecular alterations and identify erythrocyte lipidomics signatures associated with microgravity conditions. If the present results are confirmed in future studies, they may help to develop suitable treatments for astronauts after return to Earth.

Cellular and Molecular Effects of Microgravity on the Immune System: A Focus on Bioactive Lipids

“…Similarly, sphingolipids have been scarcely studied. In a recent work conducted on Caenorhabditis elegans, spaceflight was shown to induce long-lasting downregulation (i.e., up to twelve days after the experiment) on ceramide-related metabolic pathways, with the main targets being represented by N-acylsphingosine amidohydrolase-1 (ASAH1), acid sphingomyelinase-3 (ASM-3) and glucocerebrosidase-4 (GSB-4) [80]; interestingly, an impairment of sphingolipid metabolism was also confirmed in human erythrocytes cultured in clinorotation, which consisted in a significant downregulation of several sphingomyelins [81], while an alteration of the ASM axis and an impairment of ceramide production was reported in the cerebral and mesenteric artery walls of rats who underwent four weeks of hindlimb suspension [82]. Finally, FAHFAs have only been recently studied in one work, in the context of cosmic radiations, where they were found to be reduced-much like lysoglycerophospholipids and sphingolipids-in the serum of mice who underwent long-term brain irradiation with γ rays [83].…”