Nerve growth factor and epidermal growth factor rescue PC12 cells from programmed cell death induced by etoposide: distinct modes of protection against cell death by growth factors and a protein-synthesis inhibitor.
A rat pheochromocytoma cell line (PC12 cells) died within 24 h in the presence of etoposide (1-40 micrograms/ml), an inhibitor of topoisomerase II. This cytotoxic effect was prevented by either nerve growth (NGF) or epidermal growth factor (EGF). Cycloheximide and actinomycin D also suppressed the cell death as well. Furthermore, a difference among protective modes against etoposide-induced death by growth factors and a protein-synthesis inhibitor was observed: the protective effect of either NGF or EGF remained rather constant as a function of incubation time with etoposide whereas that of cycloheximide declined. These results indicate that etoposide induces programmed death in PC12 cells and that prevention of the programmed cell death by both NGF and EGF is mainly due to inactivation of molecules involved in the death processes rather than suppression of specific protein and/or mRNA synthesis.
Biochemical Research Laboratory, Morinaga Milk Industry Co. Ltd., Kanagawa, Japan.
M
M
Nakajima
K
K
Kashiwagi
J
J
Ohta
S
S
Furukawa
K
K
Hayashi
T
T
Kawashima
Y
Y
Hayashi
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D003470:Culture Media; D004247:DNA / Q000737:chemistry / Q000302:isolation & purification; D004815:Epidermal Growth Factor / Q000494:pharmacology*; D005047:Etoposide / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D009414:Nerve Growth Factors / Q000494:pharmacology*; D016716:PC12 Cells; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology*; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D059005:Topoisomerase II Inhibitors
D003470:Culture Media; D009414:Nerve Growth Factors; D011500:Protein Synthesis Inhibitors; D012333:RNA, Messenger; D059005:Topoisomerase II Inhibitors; D004815:Epidermal Growth Factor; D005047:Etoposide; D004247:DNA; D007770:L-Lactate Dehydrogenase