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ARNT2, a transcription factor for brain neuron survival?
Author(s) -
Drutel Guillaume,
Héron Anne,
Kathmann Markus,
Gros Claude,
Macé Séverine,
Plotkine Michel,
Schwartz JeanCharles,
Arrang JeanMichel
Publication year - 1999
Publication title -
european journal of neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.346
H-Index - 206
eISSN - 1460-9568
pISSN - 0953-816X
DOI - 10.1046/j.1460-9568.1999.00562.x
Subject(s) - aryl hydrocarbon receptor nuclear translocator , transcription factor , downregulation and upregulation , biology , microbiology and biotechnology , programmed cell death , neuron , apoptosis , cell cycle , transcription (linguistics) , cell , aryl hydrocarbon receptor , neuroscience , gene , biochemistry , linguistics , philosophy
The processes responsible for the limited ability to divide and long survival of neurons are not well understood but may involve aryl hydrocarbon receptor nuclear translocator 2 (ARNT2), a recently identified protein, apparently belonging to the basic helix–loop–helix superfamily of transcription factors, which is expressed almost exclusively in brain during the whole lifetime. In agreement, we show, in the rat, that ARNT2 immunoreactivity could be observed only within nuclei of brain neurons and of dividing and neuronal PC12 cells, a localization consistent with a role in transcription regulation. Cell death elicited either by focal ischaemia in brain or oxidative stress in PC12 cells was largely preceded by an almost complete suppression of ARNT2 expression. In contrast, when PC12 cell cycle progression was impaired, ARNT2 expression was enhanced. Finally, the downregulation of ARNT2 levels induced by antisense oligonucleotides prevented PC12 cell proliferation and induced apoptosis. These observations support the hypothesis that ARNT2 is a neuronal transcription factor, regulating cell cycle progression and preventing cell death, whose sustained expression might ensure brain neuron survival.