Related Experiment Video

Updated: Jul 31, 2026

Live Imaging Assay for Assessing the Roles of Ca2+ and Sphingomyelinase in the Repair of Pore-forming Toxin Wounds
18:25

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

FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology
|March 22, 2001
PubMed

Insights

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.

More Related Videos

Saturated Fatty Acids Induce Ceramide-associated Macrophage Cell Death08:26

Saturated Fatty Acids Induce Ceramide-associated Macrophage Cell Death

Published on: October 31, 2017

Inducing and Characterizing Vesicular Steatosis in Differentiated HepaRG Cells09:15

Inducing and Characterizing Vesicular Steatosis in Differentiated HepaRG Cells

Published on: July 18, 2019

Related Concept Videos

Peroxisomes01:24

Peroxisomes

Peroxisomes are specialized organelles present in fungi, plant, and animal cells. It can vary in number, size, morphology, and activity depending on the type of tissue and the nutritional state of the cell. For example, cells with active lipid metabolism, such as adipocytes, neurons, and hepatocytes, have more peroxisomes than other cells in the body. Besides their primary role in breaking down complex organic molecules, peroxisomes can also synthesize specific macromolecules and participate in...
Assembly of the Lipid Bilayer in the ER01:28

Assembly of the Lipid Bilayer in the ER

Biological membranes are more than just a barrier separating cell cytoplasm from the outside environment. They are highly dynamic and help maintain the integrity and physiological stability of the cells as well as membrane-bound organelles. Membranes also play vital roles in cell-to-cell and intracellular communication.
A large chunk of any biological membrane is composed of phospholipids. These lipids have a heterogeneous distribution across different subcellular organelles and even between...
Apoptosis01:30

Apoptosis

Apoptosis is a combination of two Greek words, 'apo' and 'ptosis,' meaning separation and falling off, respectively. Hippocrates used this word to describe gangrene, which was caused due to bandaging of fractured bones. Apoptosis was distinguished from necrosis in 1970 when John Kerr reported observations of morphological changes occurring during apoptosis. During one experiment, he observed that the disruption of blood supply to the liver tissue resulted in a size reduction of the tissue.
Caspases01:24

Caspases

Caspase, a family of cysteine proteases, serve as effectors in apoptosis. The ced3 gene in C.elegans was first identified to be involved in apoptosis. This gene encodes the ced-3 caspase that is similar to the interleukin-1-beta converting enzyme or ICE in mammals. In addition to apoptosis, caspases also function in the inflammatory response. Inflammatory caspases are essential in activating pro-inflammatory cytokines that recruit immune cells and block the replication of pathogens inside cells.
The Intrinsic Apoptotic Pathway01:31

The Intrinsic Apoptotic Pathway

Internal cellular stress, such as cellular injury or hypoxia, triggers intrinsic apoptosis. The B-cell lymphoma 2 (Bcl-2) family of proteins are the primary regulators of the intrinsic apoptotic pathway. For example, during DNA damage, checkpoint proteins, such as Ataxia Telangiectasia Mutated (ATM protein) and Checkpoints Factor-2 (Chk2) proteins, are activated. These proteins phosphorylate p53 which further activates pro-apoptotic proteins, such as Bax, Bak, PUMA, and Noxa, and inhibits...
Necrosis01:16

Necrosis

Necrosis is considered as an “accidental” or unexpected form of cell death that ends in cell lysis. The first noticeable mention of “necrosis” was in 1859 when Rudolf Virchow used this term to describe advanced tissue breakdown in his compilation titled “Cell Pathology”.
Morphological Manifestations of Necrosis
Necrotic cells show different types of morphological appearance depending on the type of tissue and infection. In coagulative necrosis, cells become anucleated and die, but their...