Document Detail

Interrupting activator protein-1 signaling in conscious rats can modify neuropeptide Y gene expression and feeding behavior of phenylpropanolamine.
MedLine Citation:
PMID:  17868324     Owner:  NLM     Status:  MEDLINE    
The mechanism for phenylpropanolamine (PPA)-induced anorexia has been attributed to its inhibitory action on hypothalamic neuropeptide Y (NPY), an orexigenic agent abundant in the brain. However, molecular mechanisms behind this effect are not well known. In this study, we investigated whether activator protein-1 (AP-1) signaling was involved. Rats were daily treated with PPA for 4 days. Changes in hypothalamic NPY, c-fos, c-jun, superoxide dismutase (SOD)-1, and SOD-2 mRNA contents were measured and compared. Results showed that c-fos and c-jun mRNA levels were increased following PPA treatment, which were relevant to a reduction in NPY mRNA level. To further determine if c-fos/c-jun genes were involved in PPA anorexia, infusions of antisense oligonucleotide into cerebroventricle were performed before daily PPA treatment in freely moving rats. Results showed that either c-fos or c-jun knock down could block PPA anorexia and restore NPY mRNA content to normal level. It is suggested that AP-1 signaling may participate in the central regulation of PPA-mediated appetite suppression via the modulation of NPY gene expression. Moreover, this modulation might be partly because of the neuroprotective effect of AP-1 since SOD gene was activated during PPA treatment.
Yih-Shou Hsieh; Shun-Fa Yang; Shu-Chen Chu; Dong-Yih Kuo
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.     Date:  2007-09-11
Journal Detail:
Title:  Journal of neurochemistry     Volume:  104     ISSN:  1471-4159     ISO Abbreviation:  J. Neurochem.     Publication Date:  2008 Jan 
Date Detail:
Created Date:  2008-01-04     Completed Date:  2008-02-18     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  2985190R     Medline TA:  J Neurochem     Country:  England    
Other Details:
Languages:  eng     Pagination:  50-61     Citation Subset:  IM    
Institute of Biochemistry, Chung Shan Medical University, Taichung City, Taiwan.
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MeSH Terms
Analysis of Variance
Appetite Depressants / administration & dosage*
Behavior, Animal / drug effects
Body Weight / drug effects
Dose-Response Relationship, Drug
Drug Administration Schedule
Eating / drug effects
Feeding Behavior / drug effects*
Gene Expression Regulation / drug effects*
Hypothalamus / drug effects
Nerve Tissue Proteins / metabolism
Neuropeptide Y / genetics,  metabolism*
Phenylpropanolamine / administration & dosage*
RNA, Messenger / metabolism
Rats, Wistar
Reverse Transcriptase Polymerase Chain Reaction / methods
Signal Transduction / physiology
Time Factors
Transcription Factor AP-1 / metabolism*
Reg. No./Substance:
0/Appetite Depressants; 0/Nerve Tissue Proteins; 0/Neuropeptide Y; 0/RNA, Messenger; 0/Transcription Factor AP-1; 14838-15-4/Phenylpropanolamine

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