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10.1074/jbc.274.15.10654

http://scihub22266oqcxt.onion/10.1074/jbc.274.15.10654
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10187863!ä!10187863

suck abstract from ncbi


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pmid10187863      J+Biol+Chem 1999 ; 274 (15): 10654-60
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  • Ceramide generation in nitric oxide-induced apoptosis Activation of magnesium-dependent neutral sphingomyelinase via caspase-3 #MMPMID10187863
  • Takeda Y; Tashima M; Takahashi A; Uchiyama T; Okazaki T
  • J Biol Chem 1999[Apr]; 274 (15): 10654-60 PMID10187863show ga
  • Sodium nitroprusside (SNP), a NO donor, has been recognized as an inducer of apoptosis in various cell lines. Here, we demonstrated the intracellular formation of ceramide, a lipid signal mediator, in SNP-induced apoptosis in human leukemia HL-60 cells and investigated the mechanisms of ceramide generation. The levels of intracellular ceramide increased to, at most, 160% of the control level in a time- and dose-dependent manner when the cells were treated with 1 mM SNP. SNP also decreased the sphingomyelin level to approximately 70% of the control level and increased magnesium-dependent neutral sphingomyelinase (N-SMase) activity to 160% of the control activity 2 h after treatment. Neither acid SMase nor magnesium-independent N-SMase was affected by SNP. Caspases are thought to be key enzymes in apoptotic cell death. Acetyl-Asp-Glu-Val-Asp-aldehyde, a synthetic tetrapeptide inhibitor of caspases, inhibited magnesiumdependent N-SMase, ceramide generation, and apoptosis. Moreover, recombinant purified caspase-3 increased magnesium-dependent N-SMase in a cell-free system. These results suggest that the findings that SNP increased ceramide generation and magnesium-dependent N-SMase activity via caspase-3 are interesting to future study to determine the relation between caspases and sphingolipid metabolites in NO-mediated signaling.
  • |Apoptosis/*drug effects[MESH]
  • |Caspase 3[MESH]
  • |Caspases/*metabolism[MESH]
  • |Ceramides/*metabolism[MESH]
  • |Enzyme Activation[MESH]
  • |Enzyme Inhibitors/pharmacology[MESH]
  • |Flow Cytometry[MESH]
  • |HL-60 Cells[MESH]
  • |Humans[MESH]
  • |Magnesium/*metabolism[MESH]
  • |Nitric Oxide/*metabolism[MESH]
  • |Nitroprusside/*pharmacology[MESH]
  • |Oligopeptides/pharmacology[MESH]
  • |Sphingomyelin Phosphodiesterase/*metabolism[MESH]


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