Insights into the molecular mechanism of apoptosis induced by TNF-α in mouse epidermal JB6-derived RT-101 cells

• Published in: Biochemical and biophysical research communications 2002-07, Vol.295 (1), p.24-30
• Main Authors: Singh, Neeta, Khanna, Neeru, Sharma, Himani, Kundu, Siddhartha, Azmi, Sameena
• Format: Article
• Language: English
• Subjects: Animals; Apoptosis; Caspase 3; Caspases - metabolism; Cell Line, Transformed; Cytochrome c Group - metabolism; Epidermal Cells; Epidermis - drug effects; Epidermis - metabolism; Flow Cytometry; Gene Expression Regulation; JB-6 cells; JNK Mitogen-Activated Protein Kinases; MAPK; Mice; Mitochondria - drug effects; Mitochondria - metabolism; Mitogen-Activated Protein Kinases - metabolism; NF-kappa B - metabolism; Signal Transduction; Superoxides - metabolism; Survival genes; Telomerase - metabolism; TNF-α; Transcription Factor AP-1 - metabolism; Transcription factors; Transcription, Genetic; Tumor Necrosis Factor-alpha - pharmacology
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/S0006-291X(02)00627-7

The mammalian response to stress is complex, often involving multiple signaling pathways that act in concert to influence cell fate. To examine potential interaction between the signaling cascade, we have focused on the effects of a model apoptotic system in a single cell type sensitive to TNF-α induced apoptosis through an examination of the relative influences of MAPKs as well as transcription factors AP-1, NF-κB, and various survival genes in determining apoptosis. Our results show that ERKs decreased transiently or remain unchanged, JNK decreased robustly, whereas c-Jun increased transiently, thereby indicating that members of MAPK family are differentially regulated in response to TNF-α induced apoptosis, whereas NF-κB protein expression decreased transiently and activity decreased at 24 h post-treatment. The survival genes Bcl-2, Bcl-XL, and survivin act independently and downstream of ERK and JNK to decrease the survival of TNF-α treated RT-101 cells. The results also suggest the involvement of the mitochondria and cytochrome c. Caspase-3 appears to be a part of a downstream event.