The role of sphingomyelin and sphingomyelin synthases in cell death, proliferation and migration—from cell and animal models to human disorders

Taniguchi, Makoto; Okazaki, Toshiro

doi:10.1016/j.bbalip.2013.12.003

Cited by 182 publications

(191 citation statements)

References 139 publications

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“…Sphingomyelins are produced from ceramides via sphingomyelin synthase, or they can generate ceramides through hydrolysis by sphingomyelinases ( Figure 5). In addition to rapidly generating ceramides as second messengers, sphingomyelins may themselves play a role in cell migration, apoptosis, autophagy, and cell survival/proliferation (22). We identified 10 specific sphingomyelins (e.g., SM.d18.1.…”

Section: Discussionmentioning

confidence: 99%

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Plasma Sphingolipids Associated with Chronic Obstructive Pulmonary Disease Phenotypes

Bowler

Jacobson

Cruickshank

et al. 2015

Am J Respir Crit Care Med

143

127

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Rationale: Chronic obstructive pulmonary disease (COPD) occurs in a minority of smokers and is characterized by intermittent exacerbations and clinical subphenotypes such as emphysema and chronic bronchitis. Although sphingolipids as a class are implicated in the pathogenesis of COPD, the particular sphingolipid species associated with COPD subphenotypes remain unknown.Objectives: To use mass spectrometry to determine which plasma sphingolipids are associated with subphenotypes of COPD.Methods: One hundred twenty-nine current and former smokers from the COPDGene cohort had 69 distinct sphingolipid species detected in plasma by targeted mass spectrometry. Of these, 23 were also measured in 131 plasma samples (117 independent subjects) using an untargeted platform in an independent laboratory. Regression analysis with adjustment for clinical covariates, correction for false discovery rate, and metaanalysis were used to test associations between COPD subphenotypes and sphingolipids. Peripheral blood mononuclear cells were used to test associations between sphingolipid gene expression and plasma sphingolipids.Measurements and Main Results: Of the measured plasma sphingolipids, five sphingomyelins were associated with emphysema; four trihexosylceramides and three dihexosylceramides were associated with COPD exacerbations. Three sphingolipids were strongly associated with sphingolipid gene expression, and 15 sphingolipid gene/metabolite pairs were differentially regulated between COPD cases and control subjects.Conclusions: There is evidence of systemic dysregulation of sphingolipid metabolism in patients with COPD. Subphenotyping suggests that sphingomyelins are strongly associated with emphysema and glycosphingolipids are associated with COPD exacerbations.

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Section: Discussionmentioning

confidence: 99%

“…ORIGINAL ARTICLE in lipid microdomains of caveolae and clathrin-coated pits (22). Sphingomyelins are produced from ceramides via sphingomyelin synthase, or they can generate ceramides through hydrolysis by sphingomyelinases ( Figure 5).…”

Section: Discussionmentioning

confidence: 99%

Plasma Sphingolipids Associated with Chronic Obstructive Pulmonary Disease Phenotypes

Bowler

Jacobson

Cruickshank

et al. 2015

Am J Respir Crit Care Med

143

127

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“…SMS can participate in inflammation, atherosclerosis, proliferation, apoptosis, differentiation and other functions (11,12). However, the association between SMS2 with the expression of DR4 and DR5, and DDP-induced apoptosis is unclear in HepG2 cells.…”

Section: Introductionmentioning

confidence: 99%

Sphingomyelin synthase 2 overexpression promotes cisplatin‑induced apoptosis of HepG2 cells

et al. 2017

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Abstract. Hepatoblastoma (HB) is the most type of common pediatric liver cancer. The primary chemotherapy drug for HB is cisplatin (DDP). However, patients readily develop intrinsic and acquired resistance, and severe side effects to treatment. Sphingomyelin synthase 2 (SMS2) is a key enzyme involved in the generation of sphingomyelin (SM), which is able to regulate cell proliferation, apoptosis and differentiation. The death receptors (DRs) have important functions in DDP-induced apoptosis. However, whether SMS2 is able to modulate cell apoptosis through the DR signaling pathway remains unknown. To investigate this question, SMS2 was overexpressed in HepG2 cells and treated with 3.5 mg/l cisplatin in the present study. After 24 h, the expression of SMS2, avian myelocytomatosis viral oncogene homolog (c-Myc), DR4, DR5 and caspase-3 was analyzed. Furthermore, cell viability was quantified, and apoptosis was assessed by western blot and flow cytometry analysis as well as Cell Counting kit-8. The results of the present study revealed that overexpression of SMS2 was able to increase the expression of c-Myc, cleaved caspase-3, DR4 and DR5 compared with the control group (P<0.05, n=3), and increase the levels of apoptosis in the SMS2 + DDP group, compared with the control (P<0.001, n=3). These results indicate that overexpression of SMS2 is able to improve sensitivity of HepG2 cells to DDP by increasing the expression of c-Myc, DR4 and DR5 in HepG2 cells. This increased sensitivity may decrease intrinsic and acquired resistance of chemotherapy in HB, and reduce the associated severe side effects in pediatric patients.

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“…Although previously considered to be simply a structural molecule, sphingomyelin (SM) has an important impact in cell-signalling through its catabolic inter-mediators, such as ceramide and sphingosine, all of these playing crucial roles in the regulation of biological processes [2][3][4]. Defects in the regulation and metabolism of SM are currently related with Niemann-Pick disease type C (NPC) although the mechanism remains to be clarified [5][6][7].…”

Section: Introductionmentioning

confidence: 99%

Sticholysin II Identifies Intracellular Lipid Deposits in Niemann Pick C Fibroblasts

Zaratti¹,

Taurisano²,

Deodato³

et al. 2016

J Toxins

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The role of sphingomyelin and sphingomyelin synthases in cell death, proliferation and migration—from cell and animal models to human disorders

Cited by 182 publications

References 139 publications

Plasma Sphingolipids Associated with Chronic Obstructive Pulmonary Disease Phenotypes

Plasma Sphingolipids Associated with Chronic Obstructive Pulmonary Disease Phenotypes

Sphingomyelin synthase 2 overexpression promotes cisplatin‑induced apoptosis of HepG2 cells

Sticholysin II Identifies Intracellular Lipid Deposits in Niemann Pick C Fibroblasts

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