Sphingolipid Catabolism and Glycerophospholipid Levels Are Altered in Erythrocytes and Plasma from Multiple Sclerosis Patients

Int J Mol Sci. 2022 Jul 8;23(14):7592. doi: 10.3390/ijms23147592.

Abstract

Multiple sclerosis (MS) is an autoimmune, inflammatory, degenerative disease of the central nervous system. Changes in lipid metabolism have been suggested to play important roles in MS pathophysiology and progression. In this work we analyzed the lipid composition and sphingolipid-catabolizing enzymes in erythrocytes and plasma from MS patients and healthy controls. We observed reduction of sphingomyelin (SM) and elevation of its products-ceramide (CER) and shingosine (SPH). These changes were supported by the detected up-regulation of the activity of acid sphingomyelinase (ASM) in MS plasma and alkaline ceramidase (ALCER) in erythrocytes from MS patients. In addition, Western blot analysis showed elevated expression of ASM, but not of ALCER. We also compared the ratios between saturated (SAT), unsaturated (UNSAT) and polyunsaturated fatty acids and suggest, based on the significant differences observed for this ratio, that the UNSAT/SAT values could serve as a marker distinguishing erythrocytes and plasma of MS from controls. In conclusion, the application of lipid analysis in the medical practice would contribute to definition of more precise diagnosis, analysis of disease progression, and evaluation of therapeutic strategies. Based on the molecular changes of blood lipids in neurodegenerative pathologies, including MS, clinical lipidomic analytical approaches could become a promising contemporary tool for personalized medicine.

Keywords: acid sphingomyelinase; alkaline ceramidase; ceramide; fatty acids; multiple sclerosis; oxidative stress; sphingolipids; sphingosine.

MeSH terms

  • Alkaline Ceramidase / metabolism
  • Ceramides / metabolism
  • Erythrocytes / metabolism
  • Glycerophospholipids* / metabolism
  • Humans
  • Multiple Sclerosis* / metabolism
  • Sphingolipids / metabolism

Substances

  • Ceramides
  • Glycerophospholipids
  • Sphingolipids
  • Alkaline Ceramidase