-
Biomolecules Oct 2020Sphingolipids (SLs) are critical components of membrane bilayers that play a crucial role in their physico-chemical properties. Ceramide is the prototype and most... (Review)
Review
Sphingolipids (SLs) are critical components of membrane bilayers that play a crucial role in their physico-chemical properties. Ceramide is the prototype and most studied SL due to its role as a second messenger in the regulation of multiple signaling pathways and cellular processes. Ceramide is a heterogeneous lipid entity determined by the length of the fatty acyl chain linked to its carbon backbone sphingosine, which can be generated either by de novo synthesis from serine and palmitoyl-CoA in the endoplasmic reticulum or via sphingomyelin (SM) hydrolysis by sphingomyelinases (SMases). Unlike de novo synthesis, SMase-induced SM hydrolysis represents a rapid and transient mechanism of ceramide generation in specific intracellular sites that accounts for the diverse biological effects of ceramide. Several SMases have been described at the molecular level, which exhibit different pH requirements for activity: neutral, acid or alkaline. Among the SMases, the neutral (NSMase) and acid (ASMase) are the best characterized for their contribution to signaling pathways and role in diverse pathologies, including liver diseases. As part of a Special Issue (Phospholipases: From Structure to Biological Function), the present invited review summarizes the physiological functions of NSMase and ASMase and their role in chronic and metabolic liver diseases, of which the most relevant is nonalcoholic steatohepatitis and its progression to hepatocellular carcinoma, due to the association with the obesity and type 2 diabetes epidemic. A better understanding of the regulation and role of SMases in liver pathology may offer the opportunity for novel treatments of liver diseases.
Topics: Ceramides; Diabetes Mellitus, Type 2; Humans; Liver; Liver Diseases; Signal Transduction; Sphingolipids; Sphingomyelin Phosphodiesterase; Sphingomyelins
PubMed: 33143193
DOI: 10.3390/biom10111497 -
Biochemical and Biophysical Research... Dec 2022Sphingomyelin has been considered as a merely structural lipid for many years. However, this organelle-specific lipid has many other roles, including increasing membrane... (Review)
Review
Sphingomyelin has been considered as a merely structural lipid for many years. However, this organelle-specific lipid has many other roles, including increasing membrane molecular order, acting as a source of ceramide in cell signaling and apoptosis, and forming clusters/nanodomains with cholesterol and ceramide. This contribution is dedicated to Professor E. Carafoli, on occasion of his 90th anniversary.
Topics: Sphingomyelins; Ceramides; Cholesterol; Apoptosis; Sphingomyelin Phosphodiesterase
PubMed: 36344153
DOI: 10.1016/j.bbrc.2022.08.074 -
International Journal of Molecular... Aug 2020Lipid rafts are dynamic assemblies of glycosphingolipids, sphingomyelin, cholesterol, and specific proteins which are stabilized into platforms involved in the... (Review)
Review
Lipid rafts are dynamic assemblies of glycosphingolipids, sphingomyelin, cholesterol, and specific proteins which are stabilized into platforms involved in the regulation of vital cellular processes. The rafts at the cell surface play important functions in signal transduction. Recent reports have demonstrated that lipid rafts are spatially and compositionally heterogeneous in the single-cell membrane. In this review, we summarize our recent data on living platelets using two specific probes of raft components: lysenin as a probe of sphingomyelin-rich rafts and BCθ as a probe of cholesterol-rich rafts. Sphingomyelin-rich rafts that are spatially and functionally distinct from the cholesterol-rich rafts were found at spreading platelets. Fibrin is translocated to sphingomyelin-rich rafts and platelet sphingomyelin-rich rafts act as platforms where extracellular fibrin and intracellular actomyosin join to promote clot retraction. On the other hand, the collagen receptor glycoprotein VI is known to be translocated to cholesterol-rich rafts during platelet adhesion to collagen. Furthermore, the functional roles of platelet glycosphingolipids and platelet raft-binding proteins including G protein-coupled receptors, stomatin, prohibitin, flotillin, and HflK/C-domain protein family, tetraspanin family, and calcium channels are discussed.
Topics: Animals; Blood Platelets; Cell Membrane; Cholesterol; Fibrin; Glycosphingolipids; Humans; Membrane Microdomains; Signal Transduction; Sphingomyelins
PubMed: 32748854
DOI: 10.3390/ijms21155539 -
Cells Mar 2022The recent discovery demonstrating that the leakage of cathepsin B from mitotic lysosomes assists mitotic chromosome segregation indicates that lysosomal membrane...
The recent discovery demonstrating that the leakage of cathepsin B from mitotic lysosomes assists mitotic chromosome segregation indicates that lysosomal membrane integrity can be spatiotemporally regulated. Unlike many other organelles, structural and functional alterations of lysosomes during mitosis remain, however, largely uncharted. Here, we demonstrate substantial differences in lysosomal proteome, lipidome, size, and pH between lysosomes that were isolated from human U2OS osteosarcoma cells either in mitosis or in interphase. The combination of pharmacological synchronization and mitotic shake-off yielded ~68% of cells in mitosis allowing us to investigate mitosis-specific lysosomal changes by comparing cell populations that were highly enriched in mitotic cells to those mainly in the G1 or G2 phases of the cell cycle. Mitotic cells had significantly reduced levels of lysosomal-associated membrane protein (LAMP) 1 and the active forms of lysosomal cathepsin B protease. Similar trends were observed in levels of acid sphingomyelinase and most other lysosomal proteins that were studied. The altered protein content was accompanied by increases in the size and pH of LAMP2-positive vesicles. Moreover, mass spectrometry-based shotgun lipidomics of purified lysosomes revealed elevated levels of sphingolipids, especially sphingomyelin and hexocylceramide, and lysoglyserophospholipids in mitotic lysosomes. Interestingly, LAMPs and acid sphingomyelinase have been reported to stabilize lysosomal membranes, whereas sphingomyelin and lysoglyserophospholipids have an opposite effect. Thus, the observed lysosomal changes during the cell cycle may partially explain the reduced lysosomal membrane integrity in mitotic cells.
Topics: Cathepsin B; Chromosome Segregation; Humans; Lysosomal-Associated Membrane Protein 1; Lysosomes; Mitosis; Sphingomyelin Phosphodiesterase; Sphingomyelins
PubMed: 35269496
DOI: 10.3390/cells11050875 -
Biomolecules Sep 2021Advances over the past decade have improved our understanding of the role of sphingolipid in the onset and progression of Parkinson's disease. Much attention has been... (Review)
Review
Advances over the past decade have improved our understanding of the role of sphingolipid in the onset and progression of Parkinson's disease. Much attention has been paid to ceramide derived molecules, especially glucocerebroside, and little on sphingomyelin, a critical molecule for brain physiopathology. Sphingomyelin has been proposed to be involved in PD due to its presence in the myelin sheath and for its role in nerve impulse transmission, in presynaptic plasticity, and in neurotransmitter receptor localization. The analysis of sphingomyelin-metabolizing enzymes, the development of specific inhibitors, and advanced mass spectrometry have all provided insight into the signaling mechanisms of sphingomyelin and its implications in Parkinson's disease. This review describes in vitro and in vivo studies with often conflicting results. We focus on the synthesis and degradation enzymes of sphingomyelin, highlighting the genetic risks and the molecular alterations associated with Parkinson's disease.
Topics: Animals; Brain; Genetic Predisposition to Disease; Humans; Metabolome; Models, Biological; Parkinson Disease; Sphingomyelins
PubMed: 34572524
DOI: 10.3390/biom11091311 -
Biochimica Et Biophysica Acta Oct 2016Synthetic lipids and surfactants that do not exist in biological systems have been used for the last few decades in both basic and applied science. The most notable... (Review)
Review
Synthetic lipids and surfactants that do not exist in biological systems have been used for the last few decades in both basic and applied science. The most notable applications for synthetic lipids and surfactants are drug delivery, gene transfection, as reporting molecules, and as support for structural lipid biology. In this review, we describe the potential of the synergistic combination of computational and experimental methodologies to study the behavior of synthetic lipids and surfactants embedded in lipid membranes and liposomes. We focused on select cases in which molecular dynamics simulations were used to complement experimental studies aiming to understand the structure and properties of new compounds at the atomistic level. We also describe cases in which molecular dynamics simulations were used to design new synthetic lipids and surfactants, as well as emerging fields for the application of these compounds. This article is part of a Special Issue entitled: Biosimulations edited by Ilpo Vattulainen and Tomasz Róg.
Topics: Drug Delivery Systems; Lipid Bilayers; Lipids; Molecular Dynamics Simulation; Phosphatidylcholines; Sphingomyelins; Spin Labels; Structure-Activity Relationship; Surface-Active Agents; Transfection
PubMed: 26946243
DOI: 10.1016/j.bbamem.2016.02.038 -
International Journal of Molecular... Aug 2022Spanish or Spanish-speaking scientists represent a remarkably populated group within the scientific community studying pore-forming proteins. Some of these scientists,... (Review)
Review
Spanish or Spanish-speaking scientists represent a remarkably populated group within the scientific community studying pore-forming proteins. Some of these scientists, ourselves included, focus on the study of actinoporins, a fascinating group of metamorphic pore-forming proteins produced within the venom of several sea anemones. These toxic proteins can spontaneously transit from a water-soluble fold to an integral membrane ensemble because they specifically recognize sphingomyelin in the membrane. Once they bind to the bilayer, they subsequently oligomerize into a pore that triggers cell-death by osmotic shock. In addition to sphingomyelin, some actinoporins are especially sensible to some other membrane components such as cholesterol. Our group from Universidad Complutense of Madrid has focused greatly on the role played by sterols in this water-membrane transition, a question which still remains only partially solved and constitutes the main core of the article below.
Topics: Animals; Cholesterol; Cnidarian Venoms; Porins; Sea Anemones; Sphingomyelins; Water
PubMed: 35955905
DOI: 10.3390/ijms23158771 -
Advances in Nutrition (Bethesda, Md.) Mar 2022Sphingomyelin (SM) is a widely occurring sphingolipid that is a major plasma membrane constituent. Milk and dairy products are rich SM sources, and human milk has high... (Review)
Review
Sphingomyelin (SM) is a widely occurring sphingolipid that is a major plasma membrane constituent. Milk and dairy products are rich SM sources, and human milk has high SM content. Numerous studies have evaluated the roles of SM in maintaining cell membrane structure and cellular signal transduction. There has been a growing interest in exploring the role of dietary SM, especially from human milk, in imparting health benefits. This review focuses on recent publications regarding SM content in several dietary sources and dietary SM metabolism. SM digestion and absorption are slow and incomplete and mainly occur in the middle sections of the small intestine. This review also evaluates the effect of dietary SM on gut health and cognitive development. Studies indicate that SM may promote gut health by reducing intestinal cholesterol absorption in adults. However, there has been a lack of data supporting clinical trials. An association between milk SM and neural development is evident before childhood. Hence, additional studies and well-designed randomized controlled trials that incorporate dietary SM evaluation, SM metabolism, and its long-term functions on infants and children are required.
Topics: Child; Adult; Infant; Humans; Animals; Sphingomyelins; Diet; Cognition; Milk
PubMed: 34549256
DOI: 10.1093/advances/nmab117 -
Biochimica Et Biophysica Acta.... Jul 2019Ceramide phosphoethanolamine (CPE) is the major sphingolipid in invertebrates and in some bacterial species. It has been also detected in mammalian cells, although only... (Review)
Review
Ceramide phosphoethanolamine (CPE) is the major sphingolipid in invertebrates and in some bacterial species. It has been also detected in mammalian cells, although only in trace amounts. Complete understanding of the biophysical and physiological relevance of CPE is still lacking, and its biological role is still an open question. CPE differs in its biosynthetic mechanisms from sphingomyelin, due to the specific CPE synthase in invertebrates. In contrast to well-established sphingomyelin/cholesterol interactions that result in the formation of ordered membrane domains, the formation of ordered CPE/cholesterol domains is not favored. CPE might be crucial for the early development of Drosophila melanogaster, and it might be involved in the developmental stages of Trypanosoma brucei. As a Bacteroidetes-associated sphingolipid, CPE might also be involved in maintenance of these bacteria in their ecological niches. Therefore, efficient detection of CPE in biological systems is needed to better define its distribution and biological role(s).
Topics: Animals; Cell Membrane; Insecta; Membrane Lipids; Sphingomyelins
PubMed: 31067435
DOI: 10.1016/j.bbamem.2019.05.001 -
Biochimica Et Biophysica Acta. Proteins... Oct 2021Actinoporins constitute a family of α pore-forming toxins produced by sea anemones. The soluble fold of these proteins consists of a β-sandwich flanked by two... (Review)
Review
Actinoporins constitute a family of α pore-forming toxins produced by sea anemones. The soluble fold of these proteins consists of a β-sandwich flanked by two α-helices. Actinoporins exert their activity by specifically recognizing sphingomyelin at their target membranes. Once there, they penetrate the membrane with their N-terminal α-helices, a process that leads to the formation of cation-selective pores. These pores kill the target cells by provoking an osmotic shock on them. In this review, we examine the role and relevance of the structural features of actinoporins, down to the residue level. We look at the specific amino acids that play significant roles in the function of actinoporins and their fold. Particular emphasis is given to those residues that display a high degree of conservation across the actinoporin sequences known to date. In light of the latest findings in the field, the membrane requirements for pore formation, the effect of lipid composition, and the process of pore formation are also discussed.
Topics: Amino Acid Motifs; Animals; Cell Membrane; Models, Molecular; Pore Forming Cytotoxic Proteins; Protein Structure, Secondary; Sea Anemones; Sphingomyelins
PubMed: 34246789
DOI: 10.1016/j.bbapap.2021.140696