J Korean Neurol Assoc.  2009 Aug;27(3):243-250.

Prostaglandin E2 Attenuates 7-Ketocholesterol Toxicity by Suppressing Changes in Mitochondria-Associated Cell Death Process

• Ahn KM
• Lee SY
• Han JH
• Kim DE
• Lee CS

Abstract

BACKGROUND: It has been shown that defects in mitochondrial function are involved in the induction of neuronal cell injury. Prostanoids such as prostaglandin E2 (PGE2) are thought to play an important role in inflammation and neurologic disorders. However, the effect of PGE2 on cholesterol-oxidation-product-induced neuronal cell injury remains uncertain.
METHODS
The effect of PGE2 on toxicity of 7-ketocholesterol (7-KCS) was assessed in PC12 cells that were differentiated following treatment with nerve growth factor. The mitochondria-mediated apoptotic process was evaluated by examining the inhibitory effect of PGE2 on 7-KCS-induced toxicity.
RESULTS
7-KCS induced BID cleavage, increased the production of proapoptotic Bax protein, decreased antiapoptotic Bcl-2, increased p53, and promoted cytochrome c release in the cytosolic fraction, which subsequently elicited the activation of caspase-3, DNA fragmentation, and cell death. Treatment with PGE2 inhibited this 7-KCS-induced apoptotic process and cell death.
CONCLUSIONS
The results show that PGE2 inhibits 7-KCS-induced toxicity in differentiated PC12 cells by suppressing the mitochondria-mediated apoptotic process. PGE2 may protect against cholesterol-oxidation-product-induced neuronal cell injury.

Keyword

Prostaglandin E2; 7-Ketocholesterol; PC12 cells; Mitochondria; Cell death; Protection

MeSH Terms

Animals
bcl-2-Associated X Protein
Caspase 3
Cell Death
Cytochromes c
Cytosol
Dinoprostone
DNA Fragmentation
Inflammation
Ketocholesterols
Mitochondria
Nerve Growth Factor
Nervous System Diseases
Neurons
PC12 Cells
Prostaglandins
Caspase 3
Cytochromes c
Dinoprostone
Ketocholesterols
Nerve Growth Factor
Prostaglandins
bcl-2-Associated X Protein