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RESP18 is Involved in the Cytotoxicity of Dopaminergic Neurotoxins in MN9D Cells.
MedLine Citation:
PMID:  23319378     Owner:  NLM     Status:  Publisher    
RESP18 (Regulated endocrine-specific protein, 18 kDa) was first identified as a dopaminergic drugs-regulated intermediate pituitary transcript. RESP18 protein is a unique endoplasmic reticulum (ER) resident protein. Its functions in the brain especially in the nervous system disorders remain unknown. ER stress (ERS) has been proved to be one of the important pathogenesis of neurodegenerative diseases, including Parkinson's disease (PD). Here, we explored the association of RESP18 and ERS in cell models of PD. Dopaminergic neurotoxin 1-methyl-4-phenyl-pyridinium ion (MPP(+)), 6-hydroxydopamine (6-OHDA), and rotenone evoked dramatic MN9D cell death. The transcriptional expressions of RESP18 and two ERS markers-binding immunoglobulin protein/glucose-regulated protein 78 (BiP/GRP78) and CCAAT/enhancer-binding protein homologous protein (CHOP) manifested differential changes in MN9D cells treated with MPP(+), 6-OHDA, and rotenone. The RESP18 protein levels increased in MPP(+) and 6-OHDA-treated cells, but did not change in the cells treated with rotenone, while the protein levels of ER molecular chaperone heat shock protein 90 kDa beta member 1/glucose-regulated protein 94 (HSP90B1/GRP94) and BiP in the cells were up-regulated by MPP(+) and 6-OHDA, respectively. Salubrinal, an ERS inhibitor, significantly reduced MPP(+) and 6-OHDA-induced cell death. Moreover, ERS inducer-thapsigargin and tunicamycin, decreased the expression of RESP18, which is different from the changes of BiP, GRP94, and CHOP. Silencing RESP18 expression with Lenti-shRNA alleviated MPP(+)-induced cell death, while over-expression of RESP18 resulted in aggravated cell death induced by MPP(+) and 6-OHDA. Taken together, our results suggest that RESP18 is involved in the cytotoxicity of dopaminergic neurotoxins.
Yufang Huang; Jing Xu; Min Liang; Xiaoqi Hong; Haiyun Suo; Jie Liu; Mei Yu; Fang Huang
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2013-1-15
Journal Detail:
Title:  Neurotoxicity research     Volume:  -     ISSN:  1476-3524     ISO Abbreviation:  Neurotox Res     Publication Date:  2013 Jan 
Date Detail:
Created Date:  2013-1-15     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  100929017     Medline TA:  Neurotox Res     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
State Key Laboratory of Medical Neurobiology, Shanghai Medical College and Institutes of Brain Science, Fudan University, 138 Yixueyuan Road, Shanghai, 200032, China.
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