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Carcinogenesis Advance Access published online on February 6, 2008
Carcinogenesis, doi:10.1093/carcin/bgn036
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© The Author 2008. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

Interactions of acetylcholinesterase with caveolin-I and subsequently with cytochrome c are required for apoptosome formation

Sang Eun Park1,3, Seung Hun Jeong1, Soo-Bog Yee1, Tae Hyun Kim1, Young Hwa Soung1, Nam Chul Ha2, Nam Deuk Kim3, Jae-Yong Park4, Hae Rahn Bae5, Bong Soo Park6, Hye Jeong Lee7 and Young Hyun Yoo1

1 Department of Anatomy and Cell Biology, Dong-A University College of Medicine and Medical Science Research Center, Busan, South Korea
2 Department of Manufacturing Pharmacy (BK21 Program), The Graduate School, Pusan National University, Busan, South Korea
3 Department of Pharmacy (BK21 Program), The Graduate School, Pusan National University, Busan, South Korea
4 Department of Physiology, Institute of Health Science and Medical Research Center for Neural Dysfunction, Gyeongsang National University School of Medicine, Jinju, South Korea
5 Department of Physiology, Dong-A University College of Medicine and Medical Science Research Center, Busan, South Korea
6 Department of Oral Anatomy and Cell Biology, College of Dentistry, Pusan National University, Busan, South Korea
7 Department of Pharmacology, Dong-A University College of Medicine and Medical Science Research Center, Busan, South Korea

* To whom correspondence should be addressed: Department of Anatomy and Cell Biology, Dong-A University College of Medicine and Medical Science Research Center, 3-1 Dongdaesin-dong, Seo-gu, Busan 602-714, South Korea. Tel: 51-240-2926; Fax: 51-241-3767. E-mail address: yhyoo{at}dau.ac.kr.

Acetylcholinesterase is emerging as an important component in leading to apoptosis. Our previous study demonstrated that silencing of the acetylcholinesterase gene blocked the interaction between cytochrome c and apoptotic protease-activating factor-1 in etoposide-induced apoptosis of HT-29 cells. We undertook this study to further dissect the molecular role of acetylcholinesterase in apoptosome formation. The present study elicited that siRNA to cytochrome c gene blocked the interaction of acetylcholinesterase with apoptotic protease-activating factor-1 whereas siRNA to apoptotic protease-activating factor-1 gene did not block the interaction of acetylcholinesterase with cytochrome c, indicating that the interaction of acetylcholinesterase with cytochrome c is required for the interaction between cytochrome c and protease-activating factor-1. We further observed that acetylcholinesterase is localized to caveolae via interacting with caveolin-1 during apoptosis and that the disruption of caveolae prevented apoptosome formation. These data indicate that the interactions of acetylcholinesterase with caveolin-1 and subsequently with cytochrome c appear to be indispensable for apoptosome formation.

Key Words: Acetylcholineseterase • Apoptosome • Apaf-1 • cytochrome c • caveolin-1

Received November 30, 2007; revised January 17, 2008; accepted January 26, 2008.


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