scholarly journals Programmed cell death in the developing inner ear is balanced by nerve growth factor and insulin-like growth factor I

2002 ◽  
Vol 116 (3) ◽  
pp. 475-486 ◽  
Author(s):  
L. M. Frago
Keyword(s):  
Cell Death ◽  
Nerve Growth Factor ◽  
Growth Factor ◽  
Programmed Cell Death ◽  
Inner Ear ◽  
Insulin Like Growth Factor ◽  
Nerve Growth ◽  
Factor I ◽  
Growth Factor I

scholarly journals Nerve growth factor withdrawal-induced cell death in neuronal PC12 cells resembles that in sympathetic neurons.

1992 ◽  
Vol 119 (6) ◽  
pp. 1669-1680 ◽  
Author(s):  
P W Mesner ◽  
T R Winters ◽  
S H Green
Keyword(s):  
Cell Death ◽  
Protein Synthesis ◽  
Nerve Growth Factor ◽  
Growth Factor ◽  
Programmed Cell Death ◽  
Pc12 Cells ◽  
Sympathetic Neurons ◽  
Nerve Growth ◽  
Neuronal Pc12 Cells ◽  
New Protein

Previous studies have shown that in neuronal cells the developmental phenomenon of programmed cell death is an active process, requiring synthesis of both RNA and protein. This presumably reflects a requirement for novel gene products to effect cell death. It is shown here that the death of nerve growth factor-deprived neuronal PC12 cells occurs at the same rate as that of rat sympathetic neurons and, like rat sympathetic neurons, involves new transcription and translation. In nerve growth factor-deprived neuronal PC12 cells, a decline in metabolic activity, assessed by uptake of [3H]2-deoxyglucose, precedes the decline in cell number, assessed by counts of trypan blue-excluding cells. Both declines are prevented by actinomycin D and anisomycin. In contrast, the death of nonneuronal (chromaffin-like) PC12 cells is not inhibited by transcription or translation inhibitors and thus does not require new protein synthesis. DNA fragmentation by internucleosomal cleavage does not appear to be a consistent or significant aspect of cell death in sympathetic neurons, neuronal PC12 cells, or nonneuronal PC12 cells, notwithstanding that the putative nuclease inhibitor aurintricarboxylic acid protects sympathetic neurons, as well as neuronal and nonneuronal PC12 cells, from death induced by trophic factor removal. Both phenotypic classes of PC12 cells respond to aurintricarboxylic acid with similar dose-response characteristics. Our results indicate that programmed cell death in neuronal PC12 cells, but not in nonneuronal PC12 cells, resembles programmed cell death in sympathetic neurons in significant mechanistic aspects: time course, role of new protein synthesis, and lack of a significant degree of DNA fragmentation.

Pattern of expression of the jun family of transcription factors during the early development of the inner ear: implications in apoptosis

1999 ◽  
Vol 112 (22) ◽  
pp. 3967-3974
Author(s):  
C. Sanz ◽  
Y. Leon ◽  
S. Canon ◽  
L. Alvarez ◽  
F. Giraldez ◽  
...  
Keyword(s):  
Cell Death ◽  
Transcription Factors ◽  
Nerve Growth Factor ◽  
Growth Factor ◽  
Inner Ear ◽  
Otic Vesicle ◽  
Mobility Shift ◽  
Nerve Growth ◽  
Vestibular Ganglion ◽  
Amino Terminal

Jun transcription factors have been implicated in the regulation of cell proliferation, differentiation and apoptosis. We have investigated the relationship between Jun expression and cell death in the developing chicken inner ear. c-jun and junD transcripts were expressed in the epithelium of the otic placode and otic vesicle. c-jun expression was restricted to the dorsal area of the otic pit (stages 14–17), dorsal otic vesicle and cochleo-vestibular ganglion (stages 18–20). junD expression was transient and occurred in the dorsal and upper medial aspects of the otic pit and otic cup, but it was down-regulated in the otic vesicle. A parallel TUNEL analysis revealed that expression of c-jun co-located within areas of intense apoptosis. Furthermore, phosphorylation of c-Jun at serine-63 by Jun amino-terminal-kinases was detected in the dorsal otic pit, otic vesicle and cochleo-vestibular ganglion. c-Jun protein exhibited DNA binding activity, as assessed by gel mobility shift assays. The association between c-Jun and apoptosis was further demonstrated by studying nerve growth factor-induced apoptosis in cultured otic vesicles. Nerve growth factor-induced cell death and c-Jun phosphorylation that were suppressed by insulin-like growth factor-I and by viral-mediated overexpression of Raf, which had survival effects. In conclusion, the precise regulation of the expression and activity of Jun proteins in the otic primordium suggests that it may operate as a fundamental mechanism during organogenesis.

Sign in / Sign up

Export Citation Format

Share Document