NF-kappaB regulates the response of embryonic cells to heat shock.
NF-kappaB was shown previously to regulate apoptotic cell death processes in various experimental systems. However, its role in controlling teratogen-induced cell death has not been established yet. Therefore, the objective of the present study was to explore the involvement of the p65 subunit of NF-kappaB in the response of mouse embryonic fibroblasts (MEFs) to heat shock, using p65 knockout (p65-/-) cells. Indeed, we found p65-/- MEFs to be more susceptible to the exposure to heat shock, as compared with wild-type (WT) MEFs, as they demonstrated a more prominent decrease in cell survival and proliferation as well as the appearance of cells undergoing apoptotic cell death. These heat-shock-induced effects were preceded by a decrease in p65 expression in WT cells, which was accompanied by a decrease in IkappaBalpha expression in WT MEFs, while disappearing completely in p65-/- MEFs and accordingly, by an increase in p-IkappaBalpha expression in both cell lines, which was found to be more prominent in p65-/- MEFs. Interestingly, the heat shock-induced decrease in p65 expression was accompanied by an increase in HSP70 expression in both cell lines. However, it was again found to be more prominent in p65-/- MEFs. Taken together, our results suggest a protective role for the p65 subunit of NF-kappaB in mechanisms underlying the response of embryonic cells to heat shock.
Savion
S
S
Department of Cell and Developmental Biology, Sackler School of Medicine, Tel Aviv University, Ramat Aviv, Israel. shoshans@post.tau.ac.il
Sofer
M
M
Brengauz-Breitmann
M
M
Fein
A
A
Torchinsky
A
A
Toder
V
V
D000818:Animals; D017209:Apoptosis / Q000502:physiology; D002453:Cell Cycle / Q000502:physiology; D002460:Cell Line; D049109:Cell Proliferation; D002470:Cell Survival / Q000502:physiology; D004195:Disease Models, Animal; D005334:Fever / Q000503:physiopathology*; D005347:Fibroblasts / Q000502:physiology*; D005786:Gene Expression Regulation / Q000502:physiology; D018840:HSP70 Heat-Shock Proteins / Q000235:genetics / Q000502:physiology; D018869:Heat-Shock Response / Q000502:physiology*; D020672:I-kappa B Proteins / Q000235:genetics / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000235:genetics / Q000502:physiology*; D051996:Transcription Factor RelA / Q000235:genetics / Q000502:physiology*
D018840:HSP70 Heat-Shock Proteins; D020672:I-kappa B Proteins; D016328:NF-kappa B; C000606205:Nfkbia protein, mouse; D051996:Transcription Factor RelA; D000072000:NF-KappaB Inhibitor alpha