title: LPS-mediated septic shock is augmented in ceramide synthase 2 null mice due to elevated activity of TNFα-converting enzyme.
abstract: Tumor necrosis factor α (TNFα) is an inflammatory cytokine that plays an intimate role in septic shock. Injection of high levels of lipopolysaccharide induces septic shock and death in mice within 30 h, whereas ceramide synthase 2 (CerS2) null mice, defective in the synthesis of very-long acyl chain ceramides, die within ∼10 h. The augmented rate of death of CerS2 null mice is due to elevated levels of TNFα secretion as a result of enhanced activity of TNFα-converting enzyme (TACE). We discuss the relationship between the sphingolipid acyl chain length and TACE activity and the relevance of this data to septic shock.
authors.affiliation: Department of Biological Chemistry, Weizmann Institute of Science, Rehovot 76100, Israel.
authors.forename: Mohammad
authors.initials: M
authors.lastname: Ali
authors.affiliation: Department of Biological Chemistry, Weizmann Institute of Science, Rehovot 76100, Israel.
authors.forename: Ashish
authors.initials: A
authors.lastname: Saroha
authors.affiliation: Department of Biological Chemistry, Weizmann Institute of Science, Rehovot 76100, Israel.
authors.forename: Yael
authors.initials: Y
authors.lastname: Pewzner-Jung
authors.affiliation: Department of Biological Chemistry, Weizmann Institute of Science, Rehovot 76100, Israel. Electronic address: tony.futerman@weizmann.ac.il.
authors.forename: Anthony H
authors.initials: AH
authors.lastname: Futerman
mesh_terms: D051722:ADAM Proteins / Q000378:metabolism*; D000072198:ADAM17 Protein; D000818:Animals; D015153:Blotting, Western; D002478:Cells, Cultured; D002518:Ceramides / Q000378:metabolism; D015870:Gene Expression; D022781:Hepatocytes / Q000378:metabolism; D008070:Lipopolysaccharides; D008264:Macrophages / Q000378:metabolism; D018345:Mice, Knockout; D018613:Microscopy, Confocal; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012772:Shock, Septic / Q000139:chemically induced / Q000378:metabolism*; D013107:Sphingolipids / Q000378:metabolism; D051049:Sphingosine N-Acyltransferase / Q000235:genetics / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000097:blood / Q000235:genetics / Q000378:metabolism*
chemical_list: D002518:Ceramides; D008070:Lipopolysaccharides; D013107:Sphingolipids; D014409:Tumor Necrosis Factor-alpha; C580723:Cers2 protein, mouse; D051049:Sphingosine N-Acyltransferase; D051722:ADAM Proteins; D000072198:ADAM17 Protein; C000606463:Adam17 protein, mouse
keywords: Ceramide; Ceramide synthase 2; LPS-mediated sepsis; Sphingolipid; Tumor necrosis factor α; Tumor necrosis factor α converting enzyme