| Abstract | Sensitive to apoptosis gene (SAG), a novel zinc RING finger protein, exhibits anti-apoptotic and antioxidant activity against a variety of redox reagents. In the present study, we have determined that SAG suppresses 1-methyl-4-phenylpyridinium ion (MPP(+))-induced neurotoxicity via the downregulation of ROS generation and c-Jun N-terminal kinase 1 (JNK1) activity. Both transient and constitutively overexpressed SAG were found to inhibit the MPP(+)-induced neurotoxicity of SH-SY5Y neuroblastoma cells. In the SAG-expressing cells, MPP(+) induced ROS generation was suppressed to a significant degree as compared to the cells treated only with MPP(+). MPP(+)-induced JNK1 activation was also determined to be suppressed markedly by SAG. Furthermore, SAG inhibits MEKK1 dependent c-Jun transcription activity in SH-SY5Y cells. Thus, we concluded that SAG is a cellular protective molecule, which appears to function as an antioxidant, suppressing MPP(+)-induced neurotoxicity. |
| Authors | Sun-Yee Kim, Mi-Yeon Kim, Jung-Soon Mo, Jeen-Woo Park, Hee-Sae Park
(Affiliation: Hormone Research Center, School of Biological Sciences and Technology, Chonnam National University, Yongbong-dong, Buk-ku, Gwangju 500-757, Republic of Korea.)
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| Journal | Neuroscience letters
(Neurosci Lett)
Vol. 413
Issue 2
Pg. 132-6
(Feb 14 2007)
ISSN: 0304-3940 Ireland |
| PMID | 17240529
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
|
| Chemical References |
- Antioxidants
- Neurotoxins
- RNA-Binding Proteins
- RNF7 protein, human
- Reactive Oxygen Species
- 1-Methyl-4-phenylpyridinium
- JNK Mitogen-Activated Protein Kinases
- MAP Kinase Kinase Kinase 1
- MAP3K1 protein, human
- Ubiquitin-Protein Ligases
|
| Topics |
- 1-Methyl-4-phenylpyridinium
(toxicity)
- Animals
- Antioxidants
(metabolism)
- Cell Line, Tumor
- Cell Survival
(drug effects, genetics)
- Enzyme Activation
(drug effects, genetics)
- Gene Expression Regulation
(genetics)
- Humans
- JNK Mitogen-Activated Protein Kinases
(metabolism)
- MAP Kinase Kinase Kinase 1
(metabolism)
- Mice
- NIH 3T3 Cells
- Neuroblastoma
- Neurons
(drug effects, metabolism, pathology)
- Neurotoxins
(toxicity)
- Oxidative Stress
(drug effects, genetics)
- Parkinson Disease
(genetics, physiopathology, therapy)
- RNA-Binding Proteins
(genetics)
- Reactive Oxygen Species
(metabolism)
- Ubiquitin-Protein Ligases
|
