Effects of cellular aging on the induction of c-fos by antioxidant treatments.
The proto-oncogene c-fos (the cellular homolog of v-fos, Finkel-Biskis-Jenkins (FBJ) murine osteogenic sarcoma virus) encodes a major component of the activator protein-1 (AP-1) transcription factor. Serum stimulation as well as oxidizing treatments induce transitory increases in c-fos mRNA abundance. The induction of c-fos by serum stimulation is also known to decline during proliferative senesence. In this study, we examined the effects of two classes of antioxidants on the induction of c-fos in early and late passage human fetal lung fibroblasts (WI-38). N-acetyl cysteine (NAC) induces c-fos transcription in both early and late passage cells, while nordihydroguaiaretic acid (NGA) induced c-fos transcription in early passage cells but fails to stimulate it in late passage cells. Since we had previously observed an age-related decline in protein kinase C (PKC) translocation from the cytosol to the membrane, following its activation, and because PKC activation appears to be involved in the NGA induction of c-fos we examined the relative protein abundances of several PKC isoforms in early and late passage cells. Additionally, we examined the protein abundance of several members of the MAP kinase pathway which could play a role in c-fos induction by the PKC-dependent pathway. We were unable to detect PKC-beta or theta in early or late passage cells. Late passage cells contained a slightly greater abundance of PKC alpha, gamma and epsilon than cells at an early passage. No other differences in PKC isoforms or in members of the MAP kinase family were observed in early or late passage cells. These results clearly demonstrate that at least some pathways leading to c-fos induction remain intact in late passage cells. While we were unable to detect any decreases in PKC isoforms or MAP kinase proteins we cannot exclude the possibility that functional decrements accumulate in these proteins during senesence.
Keogh
B P
BP
Center for Gerontological Research, Medical College of Pennsylvania, Philadelphia 19129, USA.
Tresini
M
M
Cristofalo
V J
VJ
Allen
R G
RG
D000375:Aging / Q000378:metabolism*; D000975:Antioxidants / Q000494:pharmacology*; D015152:Blotting, Northern; D002478:Cells, Cultured; D003545:Cysteine / Q000494:pharmacology; D006801:Humans; D000090063:Proto-Oncogene Mas; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism*
D000975:Antioxidants; C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D016760:Proto-Oncogene Proteins c-fos; D003545:Cysteine