Differential Regulation of the Antiapoptotic Action of B-Cell Lymphoma 2 (Bcl-2) and B-Cell Lymphoma Extra Long (Bcl-xL) by c-Jun N-Terminal Protein Kinase (JNK) 1-Involved Pathway in Neuroglioma Cells

• Published in: Biological & Pharmaceutical Bulletin 2008/09/01, Vol.31(9), pp.1686-1690
• Main Authors: Jeong, Hyo-Soon, Choi, Hye-Yeon, Choi, Tae-Won, Kim, Bong-Woo, Kim, Jung-Hyun, Lee, Eung-Ryoung, Cho, Ssang-Goo
• Format: Article
• Language: English
• Subjects: antiapoptotic action; Antineoplastic Agents, Phytogenic - pharmacology; apoptosis; Apoptosis Regulatory Proteins - physiology; B-cell lymphoma extra long expression; bcl-X Protein - biosynthesis; bcl-X Protein - genetics; Blotting, Western; Brain Neoplasms - metabolism; c-Jun N-terminal protein kinase signaling pathway; Cell Death - drug effects; Cell Line, Tumor; Cell Survival - drug effects; DNA Fragmentation - drug effects; Enzyme Activation - drug effects; etoposide; Etoposide - pharmacology; Glioma - metabolism; Humans; Mitogen-Activated Protein Kinase 8 - biosynthesis; Mitogen-Activated Protein Kinase 8 - genetics; Proto-Oncogene Proteins c-bcl-2 - biosynthesis; Proto-Oncogene Proteins c-bcl-2 - genetics; Reverse Transcriptase Polymerase Chain Reaction; Signal Transduction - drug effects; Transfection
• ISSN: 0918-6158; 1347-5215
• DOI: 10.1248/bpb.31.1686

Here, we confirmed that stable expression of B-cell lymphoma-xL (Bcl-xL) in N18TG neuroglioma cells could suppress c-Jun N-terminal protein kinase (JNK) activation, nuclear fragmentation, and cell death caused by etoposide treatment. Moreover, additional overexpression of JNK1 led to partially antagonize the antiapoptotic environment attained by Bcl-xL, implying that JNK1-involved pathway may play a role in down-regulation of the antiapoptotic effect of Bcl-xL. However, the antagonistic effect of JNK1 on the antiapoptotic action of Bcl-xL was significantly weaker than that on the action of Bcl-2. Interestingly, we found that overexpression of JNK1 led to increase of Bcl-xL expression. Thus, these results suggest that Bcl-xL and Bcl-2 may induce its antiapoptotic effect in a different mechanism, provoking the possibility of involvement of JNK1-involved pathway in Bcl-xL expression.