Sphingolipids role in the regulation of inflammatory response: From leukocyte biology to bacterial infection

Chiricozzi, Elena; Loberto, Nicoletta; Schiumarini, Domitilla; Samarani, Maura; Mancini, Giulia; Tamanini, Anna; Lippi, Giuseppe; Dechecchi, Maria Cristina; Bassi, Rosaria; Giussani, Paola; Aureli, Massimo

doi:10.1002/jlb.3mr0717-269r

Cited by 29 publications

(29 citation statements)

References 149 publications

(269 reference statements)

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“…Such microenvironment characterized by stable interactions results instrumental for ganglioside-dependent protein-specific fine modulation. In addition, glycosphingolipid oligosaccharide chains are recognized by soluble ligands, such as that of GM1 by cholera toxin (Svennerholm 1976) and that of neutral glycolipid Gb 3 Cer by verotoxin (Lingwood 1999;Chiricozzi et al 2018b). Moreover, the GD1a and GT1b oligosaccharide chains interact with the myelin-associated glycoprotein (Schnaar and Lopez 2009) belonging to the interfacing membrane of adjacent cells.…”

Section: Discussionmentioning

confidence: 99%

GM1 promotes TrkA‐mediated neuroblastoma cell differentiation by occupying a plasma membrane domain different from TrkA

Chiricozzi

Biase

Maggioni

et al. 2019

Journal of Neurochemistry

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Recently, we highlighted that the ganglioside GM1 promotes neuroblastoma cells differentiation by activating the TrkA receptor through the formation of a TrkA–GM1 oligosaccharide complex at the cell surface. To study the TrkA–GM1 interaction, we synthesized two radioactive GM1 derivatives presenting a photoactivable nitrophenylazide group at the end of lipid moiety, 1 or at position 6 of external galactose, 2; and a radioactive oligosaccharide portion of GM1 carrying the nitrophenylazide group at position 1 of glucose, 3. The three compounds were singly administered to cultured neuroblastoma Neuro2a cells under established conditions that allow cell surface interactions. After UV activation of photoactivable compounds, the proteins were analyzed by PAGE separation. The formation of cross‐linked TrkA–GM1 derivatives complexes was identified by both radioimaging and immunoblotting. Results indicated that the administration of compounds 2 and 3, carrying the photoactivable group on the oligosaccharide, led to the formation of a radioactive TrkA complex, while the administration of compound 1 did not. This underlines that the TrkA–GM1 interaction directly involves the GM1 oligosaccharide, but not the ceramide. To better understand how GM1 relates to the TrkA, we isolated plasma membrane lipid rafts. As expected, GM1 was found in the rigid detergent‐resistant fractions, while TrkA was found as a detergent soluble fraction component. These results suggest that TrkA and GM1 belong to separate membrane domains: probably TrkA interacts by ‘flopping’ down its extracellular portion onto the membrane, approaching its interplay site to the oligosaccharide portion of GM1.

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Section: Discussionmentioning

confidence: 99%

GM1 promotes TrkA‐mediated neuroblastoma cell differentiation by occupying a plasma membrane domain different from TrkA

Chiricozzi

Biase

Maggioni

et al. 2019

Journal of Neurochemistry

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“…Ceramide (CER) and sphingosine-1-phosphate (S1P) are the major SLs that act as signalling molecules, control various cellular processes, such as cell growth, adhesion, migration, senescence, cell death and inflammatory response. [11][12][13] Notably, several SL metabolites have been associated with the development of several pathologies, including diabetes, cancer, microbial infections, neurological syndromes and cardiovascular disease. [14][15][16] Our laboratory previously reported that acid sphingomyelinase (ASM) plays an important role in glomerular injury 17,18 and inflammasome activation.…”

Section: Introductionmentioning

confidence: 99%

Medial calcification in the arterial wall of smooth muscle cell‐specific Smpd1 transgenic mice: A ceramide‐mediated vasculopathy

Bhat

Yuan

Cain

et al. 2019

J Cellular Molecular Medi

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Arterial medial calcification (AMC) is associated with crystallization of hydroxyapatite in the extracellular matrix and arterial smooth muscle cells (SMCs) leading to reduced arterial compliance. The study was performed to test whether lysosomal acid sphingomyelinase (murine gene code: Smpd1)‐derived ceramide contributes to the small extracellular vesicle (sEV) secretion from SMCs and consequently leads to AMC. In Smpd1trg/SMcre mice with SMC‐specific overexpression of Smpd1 gene, a high dose of Vit D (500 000 IU/kg/d) resulted in increased aortic and coronary AMC, associated with augmented expression of RUNX2 and osteopontin in the coronary and aortic media compared with their littermates (Smpd1trg/SMwt and WT/WT mice), indicating phenotypic switch. However, amitriptyline, an acid sphingomyelinase (ASM) inhibitor, reduced calcification and reversed phenotypic switch. Smpd1trg/SMcre mice showed increased CD63, AnX2 and ALP levels in the arterial wall, accompanied by reduced co‐localization of lysosome marker (Lamp‐1) with multivesicular body (MVB) marker (VPS16), a parameter for lysosome‐MVB interaction. All these changes related to lysosome fusion and sEV release were substantially attenuated by amitriptyline. Increased arterial stiffness and elastin disorganization were found in Smpd1trg/SMcre mice as compared to their littermates. In cultured coronary arterial SMCs (CASMCs) from Smpd1trg/SMcre mice, increased Pi concentrations led to markedly increased calcium deposition, phenotypic change and sEV secretion compared with WT CASMCs, accompanied by reduced lysosome‐MVB interaction. However, amitriptyline prevented these changes in Pi‐treated CASMCs. These data indicate that lysosomal ceramide plays a critical role in phenotype change and sEV release in SMCs, which may contribute to the arterial stiffness during the development of AMC.

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“…SLs are a class of lipids located in the plasma membrane and at intracellular organelle membranes, which have not only structural roles but also signaling function. Ceramide (Cer) and sphingosine-1-phosphate (S1P) are the main SLs that act as signaling molecules, controlling a vast number of cellular processes, such as cell growth, adhesion, migration, senescence, cell death, and inflammatory response (20)(21)(22). In these cellular activities, dynamic balance between S1P and Cer levels is crucial.…”

mentioning

confidence: 99%

Role of sphingolipids in the biogenesis and biological activity of extracellular vesicles

Verderio

Gabrielli

Giussani

2018

Journal of Lipid Research

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182

136

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Extracellular vesicles (EVs) are membrane vesicles released by both eukaryotic and prokaryotic cells; they not only serve physiological functions, such as disposal of cellular components, but also play pathophysiologic roles in inflammatory and degenerative diseases. Common molecular mechanisms for EV biogenesis are evident in different cell biological contexts across eukaryotic phyla, and inhibition of this biogenesis may provide an avenue for therapeutic research. The involvement of sphingolipids (SLs) and their enzymes on EV biogenesis and release has not received much attention in current research. Here, we review how SLs participate in EV biogenesis by shaping membrane curvature and how they contribute to EV action in target cells. First, we describe how acid and neutral SMases, by generating the constitutive SL, ceramide, facilitate biogenesis of EVs at the plasma membrane and inside the endocytic compartment. We then discuss the involvement of other SLs, such as sphingosine-1-phosphate and galactosyl-sphingosine, in EV formation and cargo sorting. Last, we look ahead at some biological effects of EVs mediated by changes in SL levels in recipient cells.

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Sphingolipids role in the regulation of inflammatory response: From leukocyte biology to bacterial infection

Cited by 29 publications

References 149 publications

GM1 promotes TrkA‐mediated neuroblastoma cell differentiation by occupying a plasma membrane domain different from TrkA

GM1 promotes TrkA‐mediated neuroblastoma cell differentiation by occupying a plasma membrane domain different from TrkA

Medial calcification in the arterial wall of smooth muscle cell‐specific Smpd1 transgenic mice: A ceramide‐mediated vasculopathy

Role of sphingolipids in the biogenesis and biological activity of extracellular vesicles

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