Bcl-2 or bcl-XL gene therapy increases neural plasticity proteins nestin and c-fos expression in PC12 cells.
The anti-apoptotic gene replacements could be an option in preventing hypoxia-induced neuronal loss. In this paper we tested the effect of anti-apoptosis (bcl-2 and bcl-XL) gene transfer on cell plasticity. Nestin, synapsin-1 and c-fos genes and proteins expression were measured in PC12 cells in normal condition, and after hypoxia/re-oxygenation. Gene delivery results a significant increase in both bcl-2 and bcl-XL gene expression. Hypoxia (1h)/re-oxygenation (24h) have a detrimental effect upon cultured cells by increasing the pro-apoptotic, bax gene and protein expression. Bcl-2 or bcl-XL gene delivery resulted in a significant increase in and the cellular levels of the corresponding mRNAs and proteins. Bcl-2 gene augmented the nestin gene and protein expression which has been compromised previously by the hypoxic event. Similarly c-fos mRNA and protein expression decreased significantly after hypoxia, while the anti-apoptotic gene treatment normalized c-fos expression. Synapsin-1 gene or protein expression remained about on the same level under normoxic conditions or following hypoxia after gene treatment. We can conclude that anti-apoptotic gene transfers activate neuronal plasticity proteins nestin and c-fos. This link on anti-apoptotic proteins and cell plasticity is a new finding.
Cardiovascular Center, Department Section of Vascularneurology, Semmelweis University, H-1122, Varosmajor str. 68, Budapest, Hungary.
Aniko
A
Gal
Klara
K
Pentelenyi
Viktoria
V
Remenyi
Edina A
EA
Wappler
Geza
G
Safrany
Judit
J
Skopal
Zoltan
Z
Nagy
D000818:Animals; D017209:Apoptosis / Q000235:genetics; D016762:Genes, fos; D015316:Genetic Therapy; D007381:Intermediate Filament Proteins / Q000235:genetics*; D009419:Nerve Tissue Proteins / Q000235:genetics*; D064231:Nestin; D009473:Neuronal Plasticity; D016716:PC12 Cells; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014161:Transduction, Genetic; D051020:bcl-X Protein / Q000235:genetics*
D007381:Intermediate Filament Proteins; D009419:Nerve Tissue Proteins; C577486:Nes protein, rat; D064231:Nestin; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; D051020:bcl-X Protein