Insights into the molecular mechanism of apoptosis induced by TNF-alpha in mouse epidermal JB6-derived RT-101 cells.
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-alpha induced apoptosis through an examination of the relative influences of MAPKs as well as transcription factors AP-1, NF-kappaB, 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-alpha induced apoptosis, whereas NF-kappaB 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-alpha 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.
Singh
Neeta
N
Department of Biochemistry, All India Institute of Medical Sciences, New Delhi 110 029, India.
Khanna
Neeru
N
Sharma
Himani
H
Kundu
Siddhartha
S
Azmi
Sameena
S
D000818:Animals; D017209:Apoptosis; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D002461:Cell Line, Transformed; D003574:Cytochrome c Group / Q000378:metabolism; D000078404:Epidermal Cells; D004817:Epidermis / Q000187:drug effects / Q000378:metabolism; D005434:Flow Cytometry; D005786:Gene Expression Regulation; D048031:JNK Mitogen-Activated Protein Kinases; D051379:Mice; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D015398:Signal Transduction; D013481:Superoxides / Q000378:metabolism; D019098:Telomerase / Q000378:metabolism; D018808:Transcription Factor AP-1 / Q000378:metabolism; D014158:Transcription, Genetic; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D003574:Cytochrome c Group; D016328:NF-kappa B; D018808:Transcription Factor AP-1; D014409:Tumor Necrosis Factor-alpha; D013481:Superoxides; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases; D019098:Telomerase; C505409:Casp3 protein, mouse; D053148:Caspase 3; D020169:Caspases