SMS overexpression and knockdown: impact on cellular sphingomyelin and diacylglycerol metabolism, and cell apoptosis

Ding, Tinbo; Li, Zhiqiang; Hailemariam, Tiruneh; Mukherjee, Sushmita; Maxfield, Frederick R.; Wu, Minchen; Jiang, Xian‐Cheng

doi:10.1194/jlr.m700401-jlr200

Cited by 89 publications

(79 citation statements)

References 48 publications

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“…These observations complement the fact that over-expression of SMS1 or SMS2 in Chinese hamster ovary (CHO) cells increased the number of detergent-insoluble microdomains and TNF-induced apoptosis. 77 In both the SMS2 KO macrophages and HEK 293 cells, NF-gB activation was one of the down-stream signaling events that were inhibited upon loss or down-regulation of SMS2, thus supporting an early report in which a link between stimulation of SM synthesis and nuclear translocation of NF-gB was established. 78 SMS1 has been also implicated in raft-dependent activation of T-cell receptor in Jurkat cells.…”

Section: Sms1 and Sms2 As Regulators Of Sm Homeostasis And Receptor-msupporting

confidence: 57%

“…77 An increase of ceramide levels was also observed upon down-regulation of either SMS1 or SMS2 in HeLa and Huh cells, 66,72,74 suggesting that changes in ceramide levels due to modulation of SMSs might be differently regulated depending on the specific cellular context.…”

Section: Sms1 and Sms2 As Regulators Of Lipid-based Signalingmentioning

confidence: 93%

“…Whereas the levels of PC do not seem to change following modulation of SMSs, 66,72,74,77 altering the expression of SMS1 or SMS2 exerts diverse responses on DAG levels. In CHO cells over-expression of SMS1 or SMS2 induced a significant accumulation of total DAG.…”

Section: Sms1 and Sms2 As Regulators Of Lipid-based Signalingmentioning

confidence: 99%

“…76 Macrophages from SMS2 KO mice showed diminished recruitment of the Toll Like Receptor 4-MD2 complex on the cell surface in response to lypopolysaccharide (LPS) treatment, consistent with the reduction of LPS-mediated apoptosis observed in THP-1-derived macrophages after siRNA-mediated down-regulation of SMS1 or SMS2. 77 Likewise, siRNA-mediated down-regulation of SMS2 in HEK 293 cells partly inhibited recruitment of the tumor necrosis factor (TNF) _ receptor 1 to detergent-resistant microdomains in response to stimulation with TNF, decreasing TNF-mediated down-stream signaling. These observations complement the fact that over-expression of SMS1 or SMS2 in Chinese hamster ovary (CHO) cells increased the number of detergent-insoluble microdomains and TNF-induced apoptosis.…”

Section: Sms1 and Sms2 As Regulators Of Sm Homeostasis And Receptor-mmentioning

confidence: 99%

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Tales and Mysteries of the Enigmatic Sphingomyelin Synthase Family

Holthuis

Luberto

2010

Advances in Experimental Medicine and Biology

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In the last five years tremendous progress has been made toward the understanding of the mechanisms that govern sphingomyelin (SM) synthesis in animal cells. In line with the complexity of most biological processes, also in the case of SM biosynthesis, the more we learn the more enigmatic and finely tuned the system appears. Therefore with this review we aim first, at highlighting the most significant discoveries that advanced our knowledge and understanding of SM biosynthesis, starting from the discovery of SM to the identification of the enzymes responsible for its production; and second, at discussing old and new riddles that such discoveries pose to current investigators.

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Section: Sms1 and Sms2 As Regulators Of Sm Homeostasis And Receptor-msupporting

confidence: 57%

Section: Sms1 and Sms2 As Regulators Of Lipid-based Signalingmentioning

confidence: 93%

Section: Sms1 and Sms2 As Regulators Of Lipid-based Signalingmentioning

confidence: 99%

Section: Sms1 and Sms2 As Regulators Of Sm Homeostasis And Receptor-mmentioning

confidence: 99%

See 2 more Smart Citations

Tales and Mysteries of the Enigmatic Sphingomyelin Synthase Family

Holthuis

Luberto

2010

Advances in Experimental Medicine and Biology

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“…Regarding the role of SMS in cell death, some studies reported that downregulation of SMS1 confers resistance to stress-induced apoptosis [40,41].…”

Section: Page 17 Of 43mentioning

confidence: 99%

The natural marine anhydrophytosphingosine, Jaspine B, induces apoptosis in melanoma cells by interfering with ceramide metabolism

Salma

Lafont

Therville

et al. 2009

Biochemical Pharmacology

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This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. A c c e p t e d M a n u s c r i p t 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65 AbstractMarine environment has frequently afforded a variety of biologically active compounds with strong anticancer and cytotoxic properties. In the present study, the mechanism of action of Jaspine B, an anhydrophytosphingosine derivative isolated from the marine sponge Jaspis sp., was investigated. Jaspine B was able to doseand time-dependently decrease the viability of murine B16 and human SK-Mel28 melanoma cells. On these cells, Jaspine B treatment triggered cell death by typical apoptosis as illustrated by phosphatidylserine externalization, the release of cytochrome c and caspase processing. These effects were associated with increased intracellular ceramide levels owing to perturbed ceramide metabolism. Indeed, Jaspine B exposure strongly inhibited the activity of sphingomyelin synthase (SMS), an enzyme that converts de novo ceramide into the membrane lipid sphingomyelin.Moreover, whereas Jaspine B-induced cell death was enhanced in SMS1-depleted cells, it was strongly inhibited in cells that stably overexpress human SMS1. Finally, the cytotoxic effects of Jaspine B truncated analogs were also shown to be dependent on SMS activity.Altogether, Jaspine B is able to kill melanoma cells by acting on SMS activity and consequently on ceramide formation, and may represent a new class of cytotoxic compounds with potential applications in anticancer melanoma therapy.

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Genotype–phenotype analysis of 4q deletion syndrome: Proposal of a critical region

Strehle¹,

Liu

Rosenfeld³

et al. 2012

American J of Med Genetics Pt A

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Chromosome 4q deletion syndrome (4q- syndrome) is a rare condition, with an estimated incidence of 1 in 100,000. Although variable, the clinical spectrum commonly includes craniofacial, developmental, digital, skeletal, and cardiac involvement. Data on the genotype-phenotype correlation within the 4q arm are limited. We present detailed clinical and genetic information by array CGH on 20 patients with 4q deletions. We identified a patient who has a ∼465 kb deletion (186,770,069-187,234,800, hg18 coordinates) in 4q35.1 with all clinical features for 4q deletion syndrome except for developmental delay, suggesting that this is a critical region for this condition and a specific gene responsible for orofacial clefts and congenital heart defects resides in this region. Since the patients with terminal deletions all had cleft palate, our results provide further evidence that a gene associated with clefts is located on the terminal segment of 4q. By comparing and contrasting our patients' genetic information and clinical features, we found significant genotype-phenotype correlations at a single gene level linking specific phenotypes to individual genes. Based on these data, we constructed a hypothetical partial phenotype-genotype map for chromosome 4q which includes BMP3, SEC31A, MAPK10, SPARCL1, DMP1, IBSP, PKD2, GRID2, PITX2, NEUROG2, ANK2, FGF2, HAND2, and DUX4 genes.

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SMS overexpression and knockdown: impact on cellular sphingomyelin and diacylglycerol metabolism, and cell apoptosis

Cited by 89 publications

References 48 publications

Tales and Mysteries of the Enigmatic Sphingomyelin Synthase Family

Tales and Mysteries of the Enigmatic Sphingomyelin Synthase Family

The natural marine anhydrophytosphingosine, Jaspine B, induces apoptosis in melanoma cells by interfering with ceramide metabolism

Genotype–phenotype analysis of 4q deletion syndrome: Proposal of a critical region

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