Views: 3 Author: Site Editor Publish Time: 2023-04-12 Origin: Site
Ceramides are a class of waxy lipid molecules.Ceramides are composed of N-acetylceramide and fatty acids.Ceramides are abundant in the cell membranes of eukaryotic cells because they are the lipid components that make up sphingomyelin, one of the main lipids in lipid bilayers.Contrary to previous assumptions that ceramides and other sphingolipids in cell membranes are purely supporting structural elements, ceramides can be involved in a variety of cellular signaling:examples include regulation of cell differentiation, proliferation and programmed cell death (PCD).The word ceramide comes from the Latin cera (wax) and amide. Ceramides are a component of vernix, a waxy or cheese-like white substance that coats the skin of newborns.
Pathways for ceramide synthesis
There are three main pathways for ceramide production.First, the sphingomyelinase pathway uses an enzyme to break down sphingomyelin in cell membranes and release ceramide.Second, a de novo pathway generates ceramides from less complex molecules.Third, in the "salvage" pathway, sphingolipids broken down to sphingosine are reutilized by reacylation to form ceramides.
The hydrolysis of sphingomyelin is catalyzed by sphingomyelinase.Since sphingomyelin is one of four common phospholipids found in the plasma membrane of cells, the implication of this method of generating ceramides is that the cell membrane is the target of extracellular signals leading to programmed cell death.It has been shown that when ionizing radiation induces apoptosis in certain cells, the radiation leads to the activation of sphingomyelinase in the cell membrane and eventually to the production of ceramide.
As a bioactive lipid, ceramide is involved in a variety of physiological functions, including apoptosis, cell growth arrest, differentiation, cellular senescence, cell migration, and adhesion.The role of ceramides and their downstream metabolites is also thought to play a role in many pathological conditions, including cancer, neurodegeneration, diabetes, microbial pathogenesis, obesity, and inflammation.Several different ceramides were effective predictors of major adverse cardiovascular events (MACE), namely C16:0, C18:0 and C24:1, although C24:0 had an inverse relationship.C16-C18 are harmful to the liver.Ceramide levels are positively correlated with liver inflammation and oxidative stress, and the development and progression of nonalcoholic fatty liver disease (NAFLD) is associated with elevated ceramide levels in hepatocytes.Dietary intake of saturated fat has been shown to increase serum ceramides and increase insulin resistance.While the initial studies showed increased insulin resistance in muscle, subsequent studies have also shown increased insulin resistance in liver and adipose tissue.Interventions that limit ceramide synthesis or increase ceramide degradation improve health outcomes (eg, reduce insulin resistance and reduce fatty liver disease).
Ceramides, when synthesized, induce insulin resistance in skeletal muscle due to saturated fat activation of TLR4 receptors. Unsaturated fats had no such effect.Ceramides induce insulin resistance in many tissues by inhibiting Akt/PKB signaling.Ceramides aggregate LDL cholesterol causing LDL to become lodged in artery walls, leading to atherosclerosis.Ceramides cause endothelial dysfunction by activating protein phosphatase 2 (PP2A).In mitochondria, ceramides inhibit the electron transport chain and induce the production of reactive oxygen species.
One of the most studied roles of ceramides is related to its function as a pro-apoptotic molecule.Apoptosis, or type I programmed cell death, is critical for maintaining normal cellular homeostasis and is an important physiological response to many forms of cellular stress.Ceramides have been found to accumulate after treatment of cells with a variety of apoptotic agents, including ionizing radiation,UV light,TNF-α, and chemotherapeutics.This suggests that ceramides play a role in the biological responses of all these drugs.Ceramides have been called "tumor suppressor lipids" for their role in inducing apoptosis in cancer cells.A number of studies have attempted to further clarify the specific role of ceramide in cell death events, and some evidence suggests that ceramide plays a role in the induction of apoptosis upstream of mitochondria.However, due to conflicting and variable studies on the role of ceramide in apoptosis, the mechanism by which this lipid regulates apoptosis remains elusive.
The stratum corneum is the outermost layer of the epidermis.It consists of terminally differentiated and enucleated keratinocytes in a lipid matrix, like "bricks and mortar".Together with cholesterol and free fatty acids, ceramides form a lipid mortar, an impermeable barrier that prevents water loss through evaporation.As a general rule of thumb, the lipid matrix of the epidermis consists of an equimolar mixture of ceramides (approximately 50% by weight),cholesterol (approximately 25% by weight) and free fatty acids (approximately 15% by weight), in which Small amounts of other lipids.Lipid barriers also prevent microbial entry.