Overexpression of MnSOD Protects Murine Fibrosarcoma Cells (FSa-II) from Apoptosis and Promotes a Differentiation Program upon Treatment with 5-Azacytidine: Involvement of MAPK and NFκB Pathways
- 1 June 2001
- journal article
- research article
- Published by Mary Ann Liebert Inc in Antioxidants and Redox Signaling
- Vol. 3 (3) , 375-386
- https://doi.org/10.1089/15230860152409022
Abstract
Stable transfection of neomycin and human manganese superoxide dismutase (MnSOD2) expression plasmids into a murine fibrosarcoma cell line (FSa-II) was previously done in our laboratory. Treatment with 10 μM 5-azacytidine induced apoptosis in the control cell line (NEO), whereas the MnSOD-overexpressing cell line (SOD-H) demonstrated differentiated-appearing morphology. The levels of the myogenic transcription factor, MyoD, and the muscle-specific marker, α-actin, were increased over time with 5-azacytidine treatment in the SOD-H cell line. Nuclear transcription factor NFκB was activated in the SOD-H cell line, whereas inhibition of NFκB activation reduced the levels of MyoD and α-actin. Members of mitogen-activated protein kinase pathway and the Raf1/MEK/ERK cascade were shown to play a positive role in this event. Overexpression of MnSOD not only can protect cells from the toxic effects of 5-azacytidine, but can also promote the fibrosarcoma cells to enter a differentiation program.Keywords
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