کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
5142669 | 1496272 | 2017 | 24 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Ceramide binding to anandamide increases its half-life and potentiates its cytotoxicity in human neuroblastoma cells
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کلمات کلیدی
AEAMTSFAAHSMasemethanandamide3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium - 3- (4،5-dimethylthiazol-2-yl) -5- (3-carboxymethoxyphenyl) -2- (4-sulfophenyl) -2H-tetrazoliumanandamide - آناندامیدendocannabinoid - آندوکانابینوئیدsphingomyelinase - اسپینگومایینازFatty acid amide hydrolase - اسید آمینه هیدرولاز اسید چربLipid domain - دامنه لیپیدceramide - سرامیدcholesterol - کلسترول
موضوعات مرتبط
مهندسی و علوم پایه
شیمی
شیمی (عمومی)
پیش نمایش صفحه اول مقاله

چکیده انگلیسی
Anandamide (AEA) is a ubiquitous lipid that exerts neurotransmitter functions but also controls important biological functions such as proliferation, survival, or programmed cell death. The latter effects are also regulated by ceramide, a lipid enzymatically generated from sphingomyelin hydrolysis by sphingomyelinase. Ceramide has been shown to increase the cellular toxicity of AEA, but the mechanisms controlling this potentiating effect remained unclear. Here we have used a panel of in silico, physicochemical, biochemical and cellular approaches to study the crosstalk between AEA and ceramide apoptotic pathways. Molecular dynamics simulations indicated that AEA and ceramide could form a stable complex in phosphatidylcholine membranes. Consistent with these data, we showed that AEA can specifically insert into ceramide monolayers whereas it did not penetrate into sphingomyelin membranes. Then we have studied the effects of ceramide on AEA-induced toxicity of human neuroblastoma cells. In these experiments, the cells have been either naturally enriched in ceramide by neutral sphingomyelinase pre-incubation or treated with C2-ceramide, a biologically active ceramide analog. Both treatments significantly increased the cytotoxicity of AEA as assessed by the MTS mitochondrial toxicity assay. This effect was correlated with the concomitant accumulation of natural ceramide (or its synthetic analog) and AEA in the cells. A kinetic study of AEA hydrolysis showed that ceramide inhibited the fatty acid amino hydrolase (FAAH) activity in cell extracts. Taken together, these data suggested that ceramide binds to AEA, increases its half-life and potentiates its cytotoxicity. Overall, these mechanisms account for a functional cross-talk between AEA and ceramide apoptotic pathways.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Chemistry and Physics of Lipids - Volume 205, June 2017, Pages 11-17
Journal: Chemistry and Physics of Lipids - Volume 205, June 2017, Pages 11-17
نویسندگان
Coralie Di Scala, Morgane Mazzarino, Nouara Yahi, Karine Varini, Nicolas Garmy, Jacques Fantini, Henri Chahinian,