Regulation of sphingomyelin metabolism

Abstract

Sphingolipids (SFs) represent a large class of lipids playing diverse functions in a vast number of physiological and pathological processes. Sphingomyelin (SM) is the most abundant SF in the cell, with ubiquitous distribution within mammalian tissues, and particularly high levels in the Central Nervous System (CNS). SM is an essential element of plasma membrane (PM) and its levels are crucial for the cell function. SM content in a cell is strictly regulated by the enzymes of SM metabolic pathways, which activities create a balance between SM synthesis and degradation. The de novo synthesis via SM synthases (SMSs) in the last step of the multi-stage process is the most important pathway of SM formation in a cell. The SM hydrolysis by sphingomyelinases (SMases) increases the concentration of ceramide (Cer), a bioactive molecule, which is involved in cellular proliferation, growth and apoptosis. By controlling the levels of SM and Cer, SMSs and SMases maintain cellular homeostasis. Enzymes of SM cycle exhibit unique properties and diverse tissue distribution. Disturbances in their activities were observed in many CNS pathologies. This review characterizes the physiological roles of SM and enzymes controlling SM levels as well as their involvement in selected pathologies of the Central Nervous System, such as ischemia/hypoxia, Alzheimer disease (AD), Parkinson disease (PD), depression, schizophrenia and Niemann Pick disease (NPD).

Metabolomic profiling of ascending thoracic aortic aneurysms and dissections – Implications for pathophysiology and biomarker discovery

“…Importantly, an active sphingomyelinase-ceramide pathway, characterised by increased levels of ceramides and metabolisation of sphingomyelins (e.g. by oxidised LDL-induced sphingomyelinase activity) leads to reduced levels of sphingomyelins [30][31][32][33]. The finding of this study, that sphingomyelins are increased in BAV-A and TAV-Diss samples suggests that these classical pro-atherogenic processes may not play a role in these forms of aortic diseases.…”

Sphingomyelin generated by sphingomyelin synthase 1 is involved in attachment and infection with Japanese encephalitis virus

“…In addition, we tested the relationship of viral infection with endogenous SMase. There are two types of SMase related to cellular SM hydrolysis, neutral SMase and acid SMase which regulate various cellular functions such as proliferation, apoptosis, autophagy, and virus infection3031. However, inhibitors of both neutral SMase (GW 4869) and acid SMase (desipramine) had no effect on JEV infection (data not shown).…”

The CD300e molecule in mice is an immune-activating receptor

“…Generation of monoclonal anti-mCD300e Ab that specifically recognize mCD300e and not other CD300 members enabled us to uncover expression profiles of mCD300e in mouse hematopoietic cells. Interestingly, mCD300e was highly expressed in CD115 + Ly-6C (30,(39)(40)(41)(42)(43). Moreover, it is interesting to speculate that mCD300e contributes to the engulfment of sphingomyelin-containing debris from damaged tissues by the patrolling monocytes (31)(32)(33)(34).…”

“…It is an essential element of plasma membrane that is crucial for cellular function (29,30). In addition, it is abundant in the central nervous system (CNS); the levels of sphingomyelin in CNS are reported to be associated with the pathologies of CNS diseases, including ischemia/hypoxia, Alzheimer disease, and Parkinson disease (30 (31)(32)(33)(34)(35)(36).…”