NAC1, a POZ/BTB protein present in the adult mammalian brain, triggers apoptosis after adenovirus-mediated overexpression in PC-12 cells.
POZ/BTB proteins influence cellular development and in some examples act as oncoproteins. However, several POZ/BTB transcription factors have been found in terminally differentiated neurons, where their functions remain unknown. One example is NAC1, a constitutively-expressed protein that can regulate behaviors associated with cocaine use. The present study represents an initial attempt to understand the actions of NAC1 within neurons by using adenoviral-mediated gene transfer into differentiated PC-12 cells. Cell survival in PC-12 cells overexpressing NAC1 was greatly reduced compared with cells infected by a control Ad-GFP. The morphological appearance of the dying cells was consistent with programmed cell death. Fragmentation of genomic DNA occurred in PC-12 cells infected with adenoviruses encoding NAC1 but not control viruses. NAC1 over expression was followed by the down regulation of the anti-apoptotic proteins Bcl-2 and Bcl-2-xl. Concurrently, levels of the pro-apoptotic proteins Bax and p53 increased following NAC1 overexpression. These observations suggest that NAC1expression in PC-12 cells induces apoptosis by altering the expression of these upstream mediators of the execution phase of programmed cell death. These findings raise the possibility that aberrantly regulated NAC1 expression in the mammalian brain may contribute to programmed cell death.
Department of Psychiatry, University of Pennsylvania School of Medicine, Philadelphia, PA, USA.
Laxminarayana
L
Korutla
Jason H
JH
Neustadter
Keith M
KM
Fournier
Scott A
SA
Mackler
D000257:Adenoviridae Infections; D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D015153:Blotting, Western; D001921:Brain / Q000502:physiology; D018014:Gene Transfer Techniques; D009419:Nerve Tissue Proteins / Q000096:biosynthesis*; D009474:Neurons / Q000473:pathology* / Q000502:physiology*; D016716:PC12 Cells; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis; D019253:Proto-Oncogene Proteins c-bcl-2; D051381:Rats; D012097:Repressor Proteins / Q000096:biosynthesis; D014157:Transcription Factors; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis; D051028:bcl-2-Associated X Protein
C402243:ABTB1 protein, human; C494828:Bax protein, rat; C108190:Nacc1 protein, rat; D009419:Nerve Tissue Proteins; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D012097:Repressor Proteins; D014157:Transcription Factors; D016159:Tumor Suppressor Protein p53; D051028:bcl-2-Associated X Protein