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PAN-811 provides neuroprotection against glutamate toxicity by suppressing activation of JNK and p38 MAPK
- Source :
-
Neuroscience Letters . Jul2007, Vol. 422 Issue 1, p64-67. 4p. - Publication Year :
- 2007
-
Abstract
- Abstract: In an earlier study, we demonstrated that PAN-811 (3-aminopyridine-2-carboxaldehyde thiosemicarbazone), a novel neuroprotectant, provides protection against glutamate, staurosporine, veratridine, or hypoxia/hypoglycemia toxicities in primary cortical neuronal cultures by upregulating Bcl-2 expression [R.-W. Chen, C. Yao, X.C. Lu, Z.-G. Jiang, R. Whipple, Z. Liao, H.A. Ghanbari, B. Almassian, F.C. Tortella, J.R. Dave. PAN-811 (3-aminopyridine-2-carboxaldehyde thiosemicarbazone), a novel neuroprotectant, elicits its function in primary neuronal cultures by upregulating Bcl-2 expression. Neuroscience 135 (2005) 191–201]. Both JNK (c-Jun N-terminal kinase) and p38 MAP (mitogen-activated protein) kinase activation have a direct inhibitory action on Bcl-2 by phosphorylation. In the present study, we continued to explore the mechanism of PAN-811 neuroprotection. Our results indicate that treatment of cultured cortical neurons with glutamate (100μM) induces phosphorylation of both JNK and p38 MAPK. Specifically, pretreatment of neurons with 10μM PAN-811 (an optimal neuroprotective concentration) for 1h, 4h, or 24h significantly suppresses glutamate-mediated activation of both JNK and p38 MAPK. Furthermore, the p38 MAPK-specific inhibitor SB203580 and the JNK-specific inhibitor SP600125 prevented glutamate-induced neuronal death in these primary cultures. Our results demonstrate that glutamate-induced phosphorylation of JNK and p38 MAPK is suppressed by PAN-811, which might contribute to Bcl-2 upregulation and PAN-811 neuroprotection. [Copyright &y& Elsevier]
- Subjects :
- *GLUTAMIC acid
*NERVOUS system
*PROTEIN kinases
*HYPOGLYCEMIC agents
Subjects
Details
- Language :
- English
- ISSN :
- 03043940
- Volume :
- 422
- Issue :
- 1
- Database :
- Academic Search Index
- Journal :
- Neuroscience Letters
- Publication Type :
- Academic Journal
- Accession number :
- 25833218
- Full Text :
- https://doi.org/10.1016/j.neulet.2007.06.004