Suppression of sphingomyelin synthase 1 by small interference RNA is associated with enhanced ceramide production and apoptosis after photodamage

Šeparović, Duška; Semaan, Louie; Tarca, Adi L.; Maitah, Ma'in Y.; Hanada, Kentaro; Bielawski, Jacek; Villani, Maristella; Luberto, Chiara

doi:10.1016/j.yexcr.2008.02.008

Cited by 52 publications

(46 citation statements)

References 37 publications

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“…On the other hand, in wild type Jurkat cells, siRNA-mediated down regulation of SMS1 enhanced accumulation of ceramides, dihydroceramides and sphingosine following photodamage, with a concomitant enhancement of apoptosis. 82 Similarly, increased apoptosis was also observed after photodamage when SMS2 was down-regulated. A comparable correlation between SMS1 expression and cell death was observed in yeast.…”

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

confidence: 93%

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 Lipid-based Signalingmentioning

confidence: 93%

Tales and Mysteries of the Enigmatic Sphingomyelin Synthase Family

Holthuis

Luberto

2010

Advances in Experimental Medicine and Biology

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“…Further DNase digestion distribution of SMS activity, Sms1 localizes at the Golgi, whereas Sms2 localizes at the Golgi and plasma membrane (14,(16)(17)(18). Modulation of Sms1 or Sms2 activity in most tested cell types has resulted in an alteration of ceramide levels, whereas changes in DAG mass have been elusive (16,(19)(20)(21)(22)(23). On the other hand, in Hela cells it has been shown that, in spite of the absence of signifi cant changes of total DAG levels upon modulation of SMSs, intracellular DAG pools (in particular at the Golgi) appeared to be altered (16).…”

Section: Rna Isolation and Reverse Transcription For Real-time Pcrmentioning

confidence: 99%

Sphingomyelin synthase 1 activity is regulated by the BCR-ABL oncogene

Burns

Subathra

Signorelli

et al. 2013

Journal of Lipid Research

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This article is available online at http://www.jlr.org Supplementary key words ceramide • diacylglycerol • imatinib mesylateSphingomyelin synthase (SMS) represents an important class of enzymes responsible for the biosynthesis of SM, a critical structural component of the plasma membrane. While producing SM from ceramide and phosphatidylcholine, SMSs also form diacylglycerol (DAG) (1-7). Therefore, the biological importance of SMSs may reside not only in the biosynthesis of SM but also in the regulation, in opposing directions, of the levels of ceramide, a bioactive molecule that mainly exerts a negative effect on cell proliferation, and DAG, a well-established mitogenic lipid (8).Indeed, increased SMS activity was observed in conditions of enhanced cell proliferation (e.g., regenerating rat liver or stimulation of quiescent astrocytes with basic FGF) (9, 10) and during cell transformation (such as hepatocellular carcinoma vs. normal liver and SV-40-transformed fibroblasts vs. their normal counterpart) (8, 11). Vice versa, inhibition of SMS activity, in a caspase-dependent manner, has been shown to precede the onset of apoptosis induced by either tumor necrosis factor in Kym-1 cells or FAS ligand in Jurkat T cells (12, 13).Two genes have been identifi ed as responsible for SMS activity in mammalian cells, SMS1 and SMS2 (14, 15). The aminoacidic sequence of the proteins encoded by these two genes mainly differs in their N-termini, with Sms1 carrying a sterile ␣ motif absent in Sms2. In agreement with previous biochemical studies assessing the intracellular Abstract Sphingomyelin synthase (SMS) produces sphingomyelin while consuming ceramide (a negative regulator of cell proliferation) and forming diacylglycerol (DAG) (a mitogenic factor). Therefore, enhanced SMS activity could favor cell proliferation. To examine if dysregulated SMS contributes to leukemogenesis, we measured SMS activity in several leukemic cell lines and found that it is highly elevated in K562 chronic myelogenous leukemia (

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“…Recently, this notion has been challenged with the observation that suppression of SMS1 by siRNA is associated with enhanced ceramide production and apoptosis after photodamage [42]. Moreover, SMS1 overexpression was partially protective against staurosporine-induced apoptosis in oligodendroglioma cells [43].…”

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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Suppression of sphingomyelin synthase 1 by small interference RNA is associated with enhanced ceramide production and apoptosis after photodamage

Cited by 52 publications

References 37 publications

Tales and Mysteries of the Enigmatic Sphingomyelin Synthase Family

Tales and Mysteries of the Enigmatic Sphingomyelin Synthase Family

Sphingomyelin synthase 1 activity is regulated by the BCR-ABL oncogene

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

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