Bcl-2 or Bcl-XL gene therapy reduces apoptosis and increases plasticity protein GAP-43 in PC12 cells.
The anti-apoptotic gene replacement could be an option in preventing hypoxia induced neuronal loss-necrosis and/or apoptosis. This intervention is however still controversial. In this paper, we tested the bcl-2 or bcl-XL anti-apoptotic gene transfers using an adenovirus vector in PC12 cells after hypoxia and re-oxygenation. Gene delivery results in a significant increase in both Bcl-2 and Bcl-XL proteins expression. Hypoxia (1h)/re-oxygenation (4-48 h) have a detrimental effect upon cultured cells by inducing increased apoptosis by 30% compared to the controls. After hypoxia the compromised mitochondrial membrane function was detected by decreased tetramethyl-rhodamine-ethylester (TMRE) staining. Anti-apoptotic genes transferred 1h after hypoxia, prevent the cell damage; the number of apoptotic cells has been reduced significantly and the gene transfers prevent mitochondrial membrane damage. Under normoxic conditions or following hypoxia the expression of plasticity protein, growth associated protein 43 (GAP-43) increased significantly by the gene treatment. We can conclude that anti-apoptotic gene transfers are not only cytoprotective as it is already documented before but these genes activate GAP-43 as well. This link on apoptotic signals and cell plasticity is a new finding.
Gal
Aniko
A
National Institute of Psychiatry and Neurology, National Stroke Center, Department Section of Vascular Neurology, Semmelweis University, Budapest, Hungary.
Szilagyi
Geza
G
Wappler
Edina
E
Safrany
Geza
G
Nagy
Zoltan
Z
D000818:Animals; D017209:Apoptosis / Q000235:genetics*; D019610:Cytoprotection / Q000235:genetics; D019922:GAP-43 Protein / Q000378:metabolism*; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors; D002534:Hypoxia, Brain / Q000235:genetics / Q000378:metabolism / Q000628:therapy; D009410:Nerve Degeneration / Q000235:genetics / Q000378:metabolism / Q000628:therapy; D009473:Neuronal Plasticity / Q000235:genetics*; D009474:Neurons / Q000378:metabolism; D009942:Organometallic Compounds; D016716:PC12 Cells; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics*; D051381:Rats; D015427:Reperfusion Injury / Q000235:genetics / Q000378:metabolism / Q000628:therapy; D051020:bcl-X Protein / Q000235:genetics*
C494813:Bcl2l1 protein, rat; D019922:GAP-43 Protein; D009942:Organometallic Compounds; D019253:Proto-Oncogene Proteins c-bcl-2; D051020:bcl-X Protein; C110932:tetramethyl rhodamine ethyl ester