Interrupting activator protein-1 signaling in conscious rats can modify neuropeptide Y gene expression and feeding behavior of phenylpropanolamine.
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.
Hsieh
Yih-Shou
YS
Institute of Biochemistry, Chung Shan Medical University, Taichung City, Taiwan.
Yang
Shun-Fa
SF
Chu
Shu-Chen
SC
Kuo
Dong-Yih
DY
D000704:Analysis of Variance; D000818:Animals; D001067:Appetite Depressants / Q000008:administration & dosage*; D001522:Behavior, Animal / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004435:Eating / Q000187:drug effects; D005247:Feeding Behavior / Q000187:drug effects*; D005786:Gene Expression Regulation / Q000187:drug effects*; D007031:Hypothalamus / Q000187:drug effects; D008297:Male; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009478:Neuropeptide Y / Q000235:genetics / Q000378:metabolism*; D010665:Phenylpropanolamine / Q000008:administration & dosage*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D015398:Signal Transduction / Q000502:physiology; D013997:Time Factors; D018808:Transcription Factor AP-1 / Q000378:metabolism*
D001067:Appetite Depressants; D009419:Nerve Tissue Proteins; D009478:Neuropeptide Y; D012333:RNA, Messenger; D018808:Transcription Factor AP-1; D010665:Phenylpropanolamine