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PAN-811 (3-aminopyridine-2-carboxaldehyde thiosemicarbazone), a novel neuroprotectant, elicits its function in primary neuronal cultures by up-regulating Bcl-2 expression.
- Source :
-
Neuroscience [Neuroscience] 2005; Vol. 135 (1), pp. 191-201. - Publication Year :
- 2005
-
Abstract
- Neurotoxicity in primary neurons was induced using hypoxia/hypoglycemia (H/H), veratridine (10microM), staurosporine (1microM) or glutamate (100microM), which resulted in 72%, 67%, 75% and 66% neuronal injury, respectively. 3-Aminopyridine-2-carboxaldehyde thiosemicarbazone (PAN-811; 10microM; Panacea Pharmaceuticals, Gaithersburg, MD) pretreatment for 24 h provided maximal neuroprotection of 89%, 42%, 47% and 89% against these toxicities, respectively. Glutamate or H/H treatment of cells increased cytosolic cytochrome c levels, which was blocked by pretreatment of cells with PAN-811. Pretreatment of neurons with PAN-811 produced a time-dependent increase in the protein level of Bcl-2, which was evident even after glutamate or H/H treatments. An up-regulation in the expression of the p53 and Bax genes was also observed following exposure to these neurotoxic insults; however, this increase was not suppressed by PAN-811 pretreatment. Functional inhibition of Bcl-2 by HA14-1 reduced the neuroprotective efficacy of PAN-811. PAN-811 treatment also abolished glutamate or H/H-mediated internucleosomal DNA fragmentation.
- Subjects :
- Animals
Apoptosis drug effects
Blotting, Western
Cell Survival drug effects
Cells, Cultured
Cytochromes c metabolism
DNA Fragmentation drug effects
Excitatory Amino Acid Antagonists toxicity
Hypoglycemia pathology
Hypoxia pathology
Rats
Rats, Sprague-Dawley
Staurosporine antagonists & inhibitors
Staurosporine toxicity
Veratridine antagonists & inhibitors
Veratridine toxicity
Genes, bcl-2 genetics
Neurons drug effects
Neuroprotective Agents pharmacology
Pyridines pharmacology
Thiosemicarbazones pharmacology
Up-Regulation drug effects
Subjects
Details
- Language :
- English
- ISSN :
- 0306-4522
- Volume :
- 135
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Neuroscience
- Publication Type :
- Academic Journal
- Accession number :
- 16084648
- Full Text :
- https://doi.org/10.1016/j.neuroscience.2005.02.002