Pubmed-entry ::= {
  pmid 20061541,
  medent {
    em std {
      year 2010,
      month 2,
      day 25
    },
    cit {
      title {
        name "Triggering role of acid sphingomyelinase in endothelial
 lysosome-membrane fusion and dysfunction in coronary arteries."
      },
      authors {
        names ml {
          "Bao JX",
          "Xia M",
          "Poklis JL",
          "Han WQ",
          "Brimson C",
          "Li PL"
        },
        affil str "Dept. of Pharmacology and Toxicology, Virginia Commonwealth
 Univ., Richmond, 23298, USA."
      },
      from journal {
        title {
          iso-jta "Am. J. Physiol. Heart Circ. Physiol.",
          ml-jta "Am J Physiol Heart Circ Physiol",
          issn "1522-1539",
          name "American journal of physiology. Heart and circulatory
 physiology"
        },
        imp {
          date std {
            year 2010,
            month 3
          },
          volume "298",
          issue "3",
          pages "H992-H1002",
          language "eng",
          pubstatus ppublish,
          history {
            {
              pubstatus aheadofprint,
              date std {
                year 2010,
                month 1,
                day 8
              }
            },
            {
              pubstatus other,
              date std {
                year 2010,
                month 1,
                day 12,
                hour 6,
                minute 0
              }
            },
            {
              pubstatus pubmed,
              date std {
                year 2010,
                month 1,
                day 12,
                hour 6,
                minute 0
              }
            },
            {
              pubstatus medline,
              date std {
                year 2010,
                month 4,
                day 3,
                hour 6,
                minute 0
              }
            }
          }
        }
      },
      ids {
        pii "00958.2009",
        doi "10.1152/ajpheart.00958.2009",
        pubmed 20061541,
        other {
          db "pmc",
          tag str "PMC2838547"
        }
      }
    },
    abstract "The present study determined whether activation of acid
 sphingomyelinase (ASM) drives membrane proximal lysosomes to fuse to the cell
 surface, facilitating membrane lipid rafts (LRs) clustering in coronary
 arterial endothelial cells (CAECs) and leading to endothelial dysfunction. By
 confocal microscopy, the activators of ASM, phosphatidylinositol (PI), and
 bis (monoacylglyceryl) phosphate (Bis), and an inducer of ASM, butyrate, were
 found to increase LRs clustering in bovine CAECs, which was blocked by
 lysosome fusion inhibitor vacuolin-1. However, arsenic trioxide (Ars), an
 inducer of de novo synthesis of ceramide, had no such effect. Similarly,
 vacuolin-1-blockable effects were observed using fluorescence resonance
 energy transfer detection. Liquid chromatography-electrospray
 ionization-tandem mass spectrometry analysis demonstrated that all of these
 treatments, even Ars, increased ceramide production in CAECs. When ASM gene
 was silenced, all treatments except Ars no longer increased ceramide levels.
 Furthermore, dynamic fluorescence monitoring in live cells showed that PI and
 Bis stimulated lysosome-membrane fusion in CAECs. Functionally, PI and Bis
 impaired endothelium-dependent vasodilation in perfused coronary arteries,
 which was blocked by vacuolin-1 and a lysosome function inhibitor,
 bafilomycine. FasL (Fas ligand), a previously confirmed lysosome fusion
 stimulator as a comparison, also produced a similar effect. It is concluded
 that ASM activation serves as a triggering mechanism and driving force,
 leading to fusion of membrane proximal lysosomes into LR clusters on the cell
 membrane of CAECs, which represents a novel mechanism mediating endothelial
 dysfunction during death receptor activation or other pathological situation.",
    mesh {
      {
        term "Animals"
      },
      {
        term "Cattle"
      },
      {
        term "Cell Membrane",
        qual {
          {
            mp TRUE,
            subh "physiology"
          }
        }
      },
      {
        term "Cells, Cultured"
      },
      {
        term "Ceramides",
        qual {
          {
            subh "metabolism"
          }
        }
      },
      {
        term "Coronary Vessels",
        qual {
          {
            subh "cytology"
          },
          {
            mp TRUE,
            subh "physiopathology"
          },
          {
            subh "ultrastructure"
          }
        }
      },
      {
        term "Endothelium, Vascular",
        qual {
          {
            subh "cytology"
          },
          {
            mp TRUE,
            subh "physiopathology"
          },
          {
            subh "ultrastructure"
          }
        }
      },
      {
        term "Fas Ligand Protein",
        qual {
          {
            subh "pharmacology"
          }
        }
      },
      {
        term "Heterocyclic Compounds with 4 or More Rings",
        qual {
          {
            subh "pharmacology"
          }
        }
      },
      {
        term "Lysosomal-Associated Membrane Protein 1",
        qual {
          {
            subh "metabolism"
          }
        }
      },
      {
        term "Lysosomes",
        qual {
          {
            mp TRUE,
            subh "physiology"
          }
        }
      },
      {
        term "Membrane Fusion",
        qual {
          {
            subh "drug effects"
          },
          {
            mp TRUE,
            subh "physiology"
          }
        }
      },
      {
        term "Membrane Microdomains",
        qual {
          {
            subh "physiology"
          }
        }
      },
      {
        term "Models, Animal"
      },
      {
        term "Sphingomyelin Phosphodiesterase",
        qual {
          {
            mp TRUE,
            subh "physiology"
          }
        }
      }
    },
    substance {
      {
        type nameonly,
        name "Ceramides"
      },
      {
        type nameonly,
        name "Fas Ligand Protein"
      },
      {
        type nameonly,
        name "Heterocyclic Compounds with 4 or More Rings"
      },
      {
        type nameonly,
        name "Lysosomal-Associated Membrane Protein 1"
      },
      {
        type nameonly,
        name "vacuolin-1"
      },
      {
        type ec,
        cit "3.1.4.12",
        name "Sphingomyelin Phosphodiesterase"
      }
    },
    idnum {
      "HL-091464/HL/NHLBI NIH HHS",
      "HL-57244/HL/NHLBI NIH HHS",
      "HL-75316/HL/NHLBI NIH HHS"
    },
    pmid 20061541,
    pub-type {
      "Journal Article",
      "Research Support, N.I.H., Extramural"
    },
    status medline
  }
}

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