| Inhibition of ceramide biosynthesis ameliorates pathological consequences of spinal cord injury. | |
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MedLine Citation:
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PMID: 18838947 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Ceramide is a sphingolipid signaling molecule with powerful proinflammatory and proapoptotic properties. The aim of this study was to investigate the role of altered ceramide metabolism in spinal cord injury. Spinal cord injury was induced by application of vascular clips (force of 24 g) to the dura via a four-level T5-T8 laminectomy. Spinal cord injury in mice resulted in severe trauma characterized by edema, neutrophil infiltration, production of a range of inflammatory mediators, tissue damage, and apoptosis. Fumonisin B1, tyclodecan-9-xanthogenate (D609), and (3-carbazol-9-yl-propyl)-[2-(3,4-dimethoxy-phenyl)-ethyl]-methylamine (NB6) inhibitors of, respectively, ceramide synthase, acid sphingomyelinase, and the secretory form of acid sphingomyelinase significantly reduced the degree of (i) ceramide formation, (ii) tissue injury, (iii) neutrophil infiltration, (iv) nitrotyrosine formation, (v) TNF-alpha and IL-1beta production and apoptosis (TUNEL staining and Bax and Bcl-2 expression). Significant improvement of motor function was observed in mice treated with inhibitors of the de novo (fumonisin B1) and sphingomyelin (D609, NB6) pathways. These results implicate ceramide in the pathogenesis of spinal cord injury, providing the rationale for development of candidates for its therapeutic inhibition. |
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Authors:
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Salvatore Cuzzocrea; Hans-Peter Deigner; Tiziana Genovese; Emanuela Mazzon; Emanuela Esposito; Concetta Crisafulli; Rosanna Di Paola; Placido Bramanti; George Matuschak; Daniela Salvemini |
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Publication Detail:
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Type: Journal Article |
Journal Detail:
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Title: Shock (Augusta, Ga.) Volume: 31 ISSN: 1540-0514 ISO Abbreviation: Shock Publication Date: 2009 Jun |
Date Detail:
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Created Date: 2009-05-15 Completed Date: 2009-08-21 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 9421564 Medline TA: Shock Country: United States |
Other Details:
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Languages: eng Pagination: 634-44 Citation Subset: IM |
Affiliation:
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Department of Clinical and Experimental Medicine and Pharmacology, University of Messina, Messina, Italy. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Antioxidants / pharmacology Apoptosis / drug effects Bridged Compounds / pharmacology Carbazoles / pharmacology Ceramides / biosynthesis*, metabolism Enzyme Inhibitors / pharmacology Fumonisins / pharmacology Immunohistochemistry In Situ Nick-End Labeling Interleukin-1beta / metabolism Male Mice Oxidoreductases / antagonists & inhibitors Random Allocation Sphingomyelin Phosphodiesterase / antagonists & inhibitors Spinal Cord Injuries / drug therapy, metabolism, pathology* Thiones / pharmacology Tumor Necrosis Factor-alpha / metabolism |
| Chemical | |
Reg. No./Substance:
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0/Antioxidants; 0/Bridged Compounds; 0/Carbazoles; 0/Ceramides; 0/Enzyme Inhibitors; 0/Fumonisins; 0/Interleukin-1beta; 0/N,N,N-(3-carbazolylpropyl)-(p-methoxyphenylethyl)methylamine; 0/Thiones; 0/Tumor Necrosis Factor-alpha; 116355-83-0/fumonisin B1; 83373-60-8/tricyclodecane-9-yl-xanthogenate; EC 1.-/Oxidoreductases; EC 1.3.1.-/dihydroceramide desaturase; EC 3.1.4.12/Sphingomyelin Phosphodiesterase |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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