SAG protects human neuroblastoma SH-SY5Y cells against 1-methyl-4-phenylpyridinium ion (MPP+)-induced cytotoxicity via the downregulation of ROS generation and JNK signaling.

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
• Journal: Neuroscience letters (Neurosci Lett) Vol. 413 Issue 2 Pg. 132-6 (Feb 14 2007) ISSN: 0304-3940 [Print] Ireland
• PMID: 17240529 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antioxidants
• Neurotoxins
• RNA-Binding Proteins
• Reactive Oxygen Species
• RNF7 protein, human
• Ubiquitin-Protein Ligases
• JNK Mitogen-Activated Protein Kinases
• MAP Kinase Kinase Kinase 1
• MAP3K1 protein, human
• 1-Methyl-4-phenylpyridinium

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