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

J Korean Neurol Assoc > Volume 27(3); 2009 > Article

Journal of the Korean Neurological Association 2009;27(3): 243-250.

사립체매개성세포사멸 억제를 통한 prostaglandin E2의 7-ketocholesterol 유발 세포독성 보호효과

안경모, 이승연 한정호 김두응 이정수

서울보훈병원 신경과, 중앙대학교 의과대학 약리학교실a

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

Kyong-Mo Ahn

Department of Neurology, Seoul Veterans Hospital, Seoul, Korea Department of Pharmacologya, College of Medicine, Chung-Ang University, Seoul , Korea

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. Key Words: Prostaglandin E2, 7-Ketocholesterol, PC12 cells, Mitochondria, Cell death, Protection