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.
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.
Kim
Sun-Yee
SY
Hormone Research Center, School of Biological Sciences and Technology, Chonnam National University, Yongbong-dong, Buk-ku, Gwangju 500-757, Republic of Korea.
Kim
Mi-Yeon
MY
Mo
Jung-Soon
JS
Park
Jeen-Woo
JW
Park
Hee-Sae
HS
D015655:1-Methyl-4-phenylpyridinium / Q000633:toxicity*; D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects / Q000235:genetics; D004789:Enzyme Activation / Q000187:drug effects / Q000235:genetics; D005786:Gene Expression Regulation / Q000235:genetics; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism*; D048728:MAP Kinase Kinase Kinase 1 / Q000378:metabolism; D051379:Mice; D041681:NIH 3T3 Cells; D009447:Neuroblastoma; D009474:Neurons / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D009498:Neurotoxins / Q000633:toxicity; D018384:Oxidative Stress / Q000187:drug effects / Q000235:genetics*; D010300:Parkinson Disease / Q000235:genetics / Q000503:physiopathology / Q000628:therapy; D016601:RNA-Binding Proteins / Q000235:genetics*; D017382:Reactive Oxygen Species / Q000378:metabolism*; D044767:Ubiquitin-Protein Ligases
D000975:Antioxidants; D009498:Neurotoxins; D016601:RNA-Binding Proteins; D017382:Reactive Oxygen Species; C118307:RNF7 protein, human; D044767:Ubiquitin-Protein Ligases; D048031:JNK Mitogen-Activated Protein Kinases; D048728:MAP Kinase Kinase Kinase 1; C482576:MAP3K1 protein, human; D015655:1-Methyl-4-phenylpyridinium