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Updated: Jul 31, 2026
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Live Imaging Assay for Assessing the Roles of Ca2+ and Sphingomyelinase in the Repair of Pore-forming Toxin Wounds
Published on: August 25, 2013
Ceramide induces aSMase expression: implications for oxLDL-induced apoptosis.
H P Deigner1, R Claus, G A Bonaterra
1Institute of Pharmaceutical Chemistry and Clinics of Anaesthesiology and Intensive Care Medicine, Jena, Germany. hans-peter.deigner@med.uni-jena.de
Summary
Oxidized LDL triggers apoptosis by increasing acid sphingomyelinase (aSMase) and ceramide. Inhibiting aSMase or using aSMase-deficient cells blocks this cell death, revealing a key pathway.
Area of Science:
- Cell Biology
- Biochemistry
- Molecular Medicine
Background:
- Sphingomyelinase (SMase) activation and ceramide production are implicated in stress-induced apoptosis.
- Oxidized low-density lipoproteins (LDL), particularly minimally modified LDL (mmLDL), are linked to cellular stress responses.
Purpose of the Study:
- To investigate the role of acid sphingomyelinase (aSMase) in apoptosis induced by minimally modified LDL (mmLDL) in human macrophages and fibroblasts.
- To elucidate the signaling pathway involving ceramide generation and aSMase expression in mmLDL-initiated apoptosis.
Main Methods:
- Assessed changes in acid sphingomyelinase (aSMase) expression and ceramide concentration in response to mmLDL.
- Utilized a specific inhibitor of aSMase expression (NB6) to block mmLDL and C6-ceramide effects.
- Examined apoptosis in hereditary aSMase-deficient fibroblasts treated with mmLDL and C6-ceramide.
Main Results:
- mmLDL treatment increased aSMase expression and ceramide levels in human macrophages and fibroblasts, correlating with apoptosis.
- The aSMase inhibitor NB6 significantly reduced mmLDL and C6-ceramide-induced apoptosis by inhibiting transcription factors Sp1 and AP-2.
- Apoptosis was completely abolished in aSMase-deficient fibroblasts, confirming the enzyme's critical role.
Conclusions:
- Enhanced ceramide generation via aSMase is essential for mmLDL-initiated apoptosis.
- A positive feedback loop exists where increased intracellular ceramide enhances aSMase expression.
- This pathway highlights a novel mechanism in the pathogenesis of cardiovascular diseases linked to oxidized LDL.
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