HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

J. Biol. Chem., Vol. 283, Issue 3, 1350-1361, January 18, 2008

This Article Full Text Full Text (PDF) All Versions of this Article: 283/3/1350    most recent M702344200v1 Submit a Letter to Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Kim, S.-Y. Articles by Juhnn, Y.-S. Search for Related Content PubMed PubMed Citation Articles by Kim, S.-Y. Articles by Juhnn, Y.-S. Social Bookmarking                      What's this?

Stimulatory Heterotrimeric GTP-binding Protein Inhibits Hydrogen Peroxide-induced Apoptosis by Repressing BAK Induction in SH-SY5Y Human Neuroblastoma Cells^*

So-Young Kim, MiRan Seo, Yeni Kim, Yun-Il Lee, Jung-Min Oh, Eun-Ah Cho, Jae-Seung Kang, and Yong-Sung Juhnn¹

From the Department of Biochemistry and Molecular Biology, Cancer Research Institute, Seoul National University College of Medicine, Seoul 110-799 and the Department of Microbiology, College of Medicine, Inha University, Incheon 402-751, Korea

Heterotrimeric stimulatory GTP-binding protein (G_s) stimulates adenylate cyclases to activate the cAMP signaling pathway. Although the cAMP pathway has been reported to be involved in apoptosis, the role of the G_s-cAMP signaling pathway during reactive oxygen species (ROS)-mediated apoptosis, which is involved in the resistance of cancer cells to chemotherapy and radiation, is not clearly understood. Thus, in this study we aimed to investigate the role of the subunit of G_s (G_s) in the ROS-induced apoptosis of cancer cells. The stable expression of constitutively active G_s (G_sQL) inhibited the hydrogen peroxide-induced apoptosis of SH-SY5Y human neuroblastoma cells and reduced the hydrogen peroxide-induced increase in Bak and the decrease in Bcl-x_L protein expression. Exogenous Bak expression abolished these inhibitory effects of G_sQL, but Bak small interfering RNA decreased hydrogen peroxide-induced apoptosis. G_s repressed hydrogen peroxide-induced Bak expression by inhibiting the transcription of Bak mRNA, which resulted from the inhibition of the hydrogen peroxide-induced activation of transcription factors such as AP1, NF-B, and NFAT. Moreover, G_s also inhibited the hydrogen peroxide-induced binding of AP1, NF-B, and NFAT to the Bak promoter. Furthermore, hydrogen peroxide-induced apoptosis was reduced by treating cells with prostaglandin E₂, which activates G_s, but this was augmented by CCPA, which activates G_i causing a decrease in cAMP levels. From the results, we conclude that G_s protects neuroblastoma cells from hydrogen peroxide-induced apoptosis by repressing Bak induction, which is mediated by the inhibition of the hydrogen peroxide-induced activations of AP1, NF-B, and NFAT through cAMP-PKA-CREB signaling system.

Received for publication, March 19, 2007 , and in revised form, October 30, 2007.

^* This work was supported by Grants M2-0408-00-0027 and M2-0513-00-0099 from the Nuclear R&D Program of the Ministry of Science & Technology and the 2007 BK21 Project for Medicine. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ To whom correspondence should be addressed: Dept. of Biochemistry and Molecular Biology, Seoul National University College of Medicine, 28 Yongon-dong, Jongno-gu, Seoul 110-799, Republic of Korea. Tel.: 82-2-740-8247; Fax: 82-2-744-4534; E-mail: juhnn{at}snu.ac.kr.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				J.-M. Oh, S.-H. Kim, Y.-I. Lee, M. Seo, S.-Y. Kim, Y.-S. Song, W.-H. Kim, and Y.-S. Juhnn Human papillomavirus E5 protein induces expression of the EP4 subtype of prostaglandin E2 receptor in cyclic AMP response element-dependent pathways in cervical cancer cells Carcinogenesis, January 1, 2009; 30(1): 141 - 149. [Abstract] [Full Text] [PDF]