Ceramide induces aSMase expression: implications for oxLDL-induced apoptosis

被引:80
作者
Deigner, HP [1 ]
Claus, R
Bonaterra, GA
Gehrke, C
Bibak, N
Blaess, M
Cantz, M
Metz, J
Kinscherf, R
机构
[1] Univ Jena, Clin Anaesthesiol, D-07740 Jena, Germany
[2] Univ Jena, Clin Intens Care Med, D-07740 Jena, Germany
[3] Univ Jena, Inst Pharmaceut Chem, D-07740 Jena, Germany
[4] Univ Heidelberg, Dept Anat & Cell Biol 3, D-69120 Heidelberg, Germany
[5] Univ Heidelberg, Inst Pathochem & Neurochem, D-69120 Heidelberg, Germany
关键词
acid sphingomyelinase; macrophages; Niemann-Pick; programmed cell death; C-6-ceramide;
D O I
10.1096/fj.15.3.807
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Sphingomyelinase (SMase) stimulation and subsequent ceramide generation are suggested to be involved in signal transduction of stress-induced apoptosis, We now show that apoptosis of human macrophages (M phi) and fibroblasts initiated by oxidized low density lipoproteins (minimally modified LDL, mmLDL) is associated with an increase in acid SMase (aSMase, E.C, 3.1.4.12) expression and ceramide concentration. Application of a novel, potent, and specific inhibitor of aSMase expression (NB6) diminished the effects of mmLDL and C-6-ceramide treatment by inhibiting transcription via Sp1 and AP-2. Moreover, apoptosis was abolished after mmLDL and C-6-ceramide treatment of hereditary aSMase-deficient fibroblasts (from Niemann-Pick patients), We suggest that in mmLDL-initiated apoptosis 1) enhanced ceramide generation via aSMase appears to be required as well as 2) a positive feedback control of aSMase expression by the increase in intracellular ceramide concentration.
引用
收藏
页码:807 / 814
页数:8
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