Cyclic GMP Mediates Apoptosis Induced by Sulindac Derivatives via Activation of c-Jun NH2-Terminal Kinase 1
作者： Yuehua Mao , Han Li , I. Bernard Weinstein , Jae-Won Soh , W. Joseph Thompson
DOI:
关键词:
摘要: Sulindac sulfone (Exisulind) induces apoptosis and exhibits cancer chemopreventive activity, but in contrast to sulindac, it does not inhibit cyclooxygenases 1 or 2. We found that sulindac two potent derivatives, CP248 CP461, inhibited the cyclic GMP (cGMP) phosphodiesterases (PDE) 2 5 human colon cells, these compounds caused rapid sustained activation of c-Jun NH2-terminal kinase (JNK1). Rapid stress-activated protein/ERK (SEK1) mitogen-activated protein (MEKK1), which are upstream JNK1, was also observed. Other increase cellular levels cGMP activated an inhibitor G (PKG), Rp-8-pCPT-cGMPS, JNK1 by derivatives. Expression a dominant-negative CP248-induced cleavage poly(ADP-ribose) polymerase, marker apoptosis. Thus, appears related induce apoptosis, at least part, through PKG, then activates MEKK1-SEK1-JNK1 cascade. These studies indicate role for PKG JNK pathway.
aacrjournals.org参考文章(34)
Thomas K Schlesinger, Gary R Fanger, Toshi Yujiri, Gary L Johnson, The TAO of MEKK Frontiers in Bioscience. ,vol. 3, pp. d1181- 1186 ,(1998) , 10.2741/A354
Strada Sj, Epstein Pm, Thompson Wj, Terasaki Wl, Assay of cyclic nucleotide phosphodiesterase and resolution of multiple molecular forms of the enzyme. Advances in cyclic nucleotide research. ,vol. 10, pp. 69- 92 ,(1979)
Tanima Gudi, Ivana Huvar, Matthias Meinecke, Suzanne M. Lohmann, Gerry R. Boss, Renate B. Pilz, Regulation of Gene Expression by cGMP-dependent Protein Kinase TRANSACTIVATION OF THE c-fos PROMOTER Journal of Biological Chemistry. ,vol. 271, pp. 4597- 4600 ,(1996) , 10.1074/JBC.271.9.4597
Marco Conti, S.-L. Catherine Jin, The molecular biology of cyclic nucleotide phosphodiesterases. Progress in Nucleic Acid Research and Molecular Biology. ,vol. 63, pp. 1- 38 ,(1999) , 10.1016/S0079-6603(08)60718-7
Min Liang Kuo, Shine Gwo Shiah, Shing Chuan Shen, Shuang En Chuang, Yat Pang Chau, Activation of c-Jun NH2-terminal Kinase and Subsequent CPP32/Yama during Topoisomerase Inhibitor β-Lapachone-induced Apoptosis through an Oxidation-dependent Pathway Cancer Research. ,vol. 59, pp. 391- 398 ,(1999)
Ronald E. Weishaar, Stephen D. Burrows, Dianne C. Kobylarz, Mary M. Quade, Dale B. Evans, Multiple molecular forms of cyclic nucleotide phosphodiesterase in cardiac and smooth muscle and in platelets: Isolation, characterization, and effects of various reference phosphodiesterase inhibitors and cardiotonic agents Biochemical Pharmacology. ,vol. 35, pp. 787- 800 ,(1986) , 10.1016/0006-2952(86)90247-9
Tushar Patel, Gregory J. Gores, Scott H. Kaufmann, The role of proteases during apoptosis. The FASEB Journal. ,vol. 10, pp. 587- 597 ,(1996) , 10.1096/FASEBJ.10.5.8621058
Nancy S. Paranka, Rajendra G. Mehta, Dennis J. Ahnen, Junxuan Lu, Henry J. Thompson, Cheng Jiang, Gary A. Piazza, Rifat Pamukcu, Sulfone Metabolite of Sulindac Inhibits Mammary Carcinogenesis Cancer Research. ,vol. 57, pp. 267- 271 ,(1997)
Kazuhito Yamamoto, Hidenori Ichijo, Stanley J. Korsmeyer, BCL-2 Is Phosphorylated and Inactivated by an ASK1/Jun N-Terminal Protein Kinase Pathway Normally Activated at G2/M Molecular and Cellular Biology. ,vol. 19, pp. 8469- 8478 ,(1999) , 10.1128/MCB.19.12.8469
Han Li, Alanna K. Rahm, Dennis J. Ahnen, Alan L. Stoumen, Tyler S. Finn, Benjamin H. Fryer, Gary A. Piazza, Rifat Pamukcu, Apoptosis Primarily Accounts for the Growth-inhibitory Properties of Sulindac Metabolites and Involves a Mechanism That Is Independent of Cyclooxygenase Inhibition, Cell Cycle Arrest, and p53 Induction Cancer Research. ,vol. 57, pp. 2452- 2459 ,(1997)