Abstract：
:Sphingolipids (SLs) have been implicated in numerous important cellular biologies; however, their study has been hindered by the complexities of SL metabolism. Furthermore, enzymes of SL metabolism represent a dynamic and interconnected network in which one metabolite can be transformed into other bioactive SLs through further metabolism, resulting in diverse cellular responses. Here we explore the effects of both lethal and sublethal doses of doxorubicin (Dox) in MCF-7 cells. The two concentrations of Dox resulted in the regulation of SLs, including accumulations in sphingosine, sphingosine-1-phosphate, dihydroceramide, and ceramide, as well as reduced levels of hexosylceramide. To further define the effects of Dox on SLs, metabolic flux experiments utilizing a d17 dihydrosphingosine probe were conducted. Results indicated the regulation of ceramidases and sphingomyelin synthase components specifically in response to the cytostatic dose. The results also unexpectedly demonstrated dose-dependent inhibition of dihydroceramide desaturase and glucosylceramide synthase in response to Dox. Taken together, this study uncovers novel targets in the SL network for the action of Dox, and the results reveal the significant complexity of SL response to even a single agent. This approach helps to define the role of specific SL enzymes, their metabolic products, and the resulting biologies in response to chemotherapeutics and other stimuli.
journal_name
J Lipid Resjournal_title
Journal of lipid researchauthors
Snider JM,Trayssac M,Clarke CJ,Schwartz N,Snider AJ,Obeid LM,Luberto C,Hannun YAdoi
10.1194/jlr.M089714subject
Has Abstractpub_date
2019-04-01 00:00:00pages
819-831issue
4eissn
0022-2275issn
1539-7262pii
jlr.M089714journal_volume
60pub_type
杂志文章abstract：:Paraoxonases (PONs) are a small family of antioxidant enzymes whose antiatherogenic activity is well known. The aim of the present study was the evaluation of the effects of moderate aerobic training on their expression using a rat model. In order to discriminate between PON1 and PON3 enzymatic activity, we took advan...
journal_title：Journal of lipid research
pub_type： 杂志文章
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更新日期：2009-10-01 00:00:00
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journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.M011817
更新日期：2011-05-01 00:00:00
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journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.M600344-JLR200
更新日期：2007-02-01 00:00:00
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journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1994-09-01 00:00:00
abstract：:Five samples from three different types of 1500-year-old Mediterranean amphorae, as well as from a contemporary oil lamp found in the same deposit, were analyzed for the presence of lipid residues. Each sample of finely ground amphorae powder weighed 1-2 g. The abundance of interfering secondary products makes thin-la...
journal_title：Journal of lipid research
pub_type： 历史文章,杂志文章
doi：
更新日期：1981-07-01 00:00:00
abstract：:Neu-Laxova syndrome (NLS) is a very rare autosomal recessive congenital disorder characterized by disturbed development of the central nervous system and the skin and caused by mutations in any of the three genes involved in de novo l-serine biosynthesis: PHGDH, PSAT1, and PSPH l-Serine is essential for the biosynthes...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.P087536
更新日期：2018-12-01 00:00:00
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journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.M054718
更新日期：2015-02-01 00:00:00
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journal_title：Journal of lipid research
pub_type： 杂志文章,随机对照试验
doi：10.1194/jlr.P093013
更新日期：2019-06-01 00:00:00
abstract：:The sphingomyelin pathway is an important signal transduction system regulating various cellular functions. However, little is known about the effect of sphingomyelin metabolites on vasomotor function. We examined the vascular effects of sphingomyelin, sphingosine, and sphingomyelinase (SPMase) in vitro. In pig corona...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1996-07-01 00:00:00
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journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1995-10-01 00:00:00
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journal_title：Journal of lipid research
pub_type： 临床试验,杂志文章,随机对照试验
doi：
更新日期：1994-04-01 00:00:00
abstract：:The accumulation of phosphatidylcholine hydroperoxide (PCOOH), a primary oxidation product of phosphatidylcholine (PC), in blood plasma and tissues has been observed in various pathological conditions, including atherosclerosis. However, the biological roles of PCOOH in these conditions remain unknown. To estimate the...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.M800582-JLR200
更新日期：2009-05-01 00:00:00
abstract：:Apolipoprotein E (apoE) polymorphism is a genetic determinant of plasma lipid levels and of coronary heart disease (CHD) risk. We determined the apoE phenotypes and plasma lipid levels in 1577 youths aged 3 to 18 years in 1980. The subjects were randomly selected from five areas of Finland. ApoE phenotyping was perfor...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1990-03-01 00:00:00
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journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1990-02-01 00:00:00
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journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1988-03-01 00:00:00
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journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.M005348
更新日期：2010-07-01 00:00:00
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journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.M085985
更新日期：2018-11-01 00:00:00
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journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.P080143
更新日期：2018-05-01 00:00:00
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journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1996-02-01 00:00:00
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journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1998-12-01 00:00:00
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journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1991-10-01 00:00:00
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journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1992-04-01 00:00:00
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journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.M048348
更新日期：2014-07-01 00:00:00
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journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1969-07-01 00:00:00
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journal_title：Journal of lipid research
pub_type： 杂志文章,评审
doi：10.1194/jlr.R063313
更新日期：2016-01-01 00:00:00
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journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1993-09-01 00:00:00
abstract：:The novel acyl-CoA:cholesterol acyltransferase (ACAT) inhibitor CP-113,818 has been characterized in vitro against ACAT isolated from liver and intestine from a variety of species including human subjects, and in vivo in cholesterol-fed rats, hamsters, rabbits, and two species of nonhuman primates. CP-113,818 is a pot...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1994-10-01 00:00:00
abstract：:ABCA12 mutations disrupt the skin barrier and cause harlequin ichthyosis. We previously showed Abca12(-/-) skin has increased glucosylceramide (GlcCer) and correspondingly lower amounts of ceramide (Cer). To examine why loss of ABCA12 leads to accumulation of GlcCer, de novo sphingolipid synthesis was assayed using [(...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.M044941
更新日期：2014-03-01 00:00:00
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journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.M073882
更新日期：2017-07-01 00:00:00
abstract：:Previous studies from our laboratory have shown that oral administration of stigmastanyl-phosphocholine (Ro 16-6532) reduces plasma cholesterol levels in experimental animals on diets free of added cholesterol. In the present study, effects of Ro 16-6532 and lovastatin on lipoprotein levels and metabolism were investi...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1995-07-01 00:00:00
