Activations of c-fos/c-jun signaling are involved in the modulation of hypothalamic superoxide dismutase (SOD) and neuropeptide Y (NPY) gene expression in amphetamine-mediated appetite suppression.
Amphetamine (AMPH) is known as an anorectic agent. The mechanism underlying the anorectic action of AMPH has been attributed to its inhibitory action on hypothalamic neuropeptide Y (NPY), an appetite stimulant in the brain. This study was aimed to examine the molecular mechanisms behind the anorectic effect of AMPH. Results showed that AMPH treatment decreased food intake, which was correlated with changes of NPY mRNA level, but increased c-fos, c-jun and superoxide dismutase (SOD) mRNA levels in hypothalamus. To determine if c-fos or c-jun was involved in the anorectic response of AMPH, infusions of antisense oligonucleotide into the brain were performed at 1 h before daily AMPH treatment in freely moving rats, and the results showed that c-fos or c-jun knockdown could block this anorectic response and restore NPY mRNA level. Moreover, c-fos or c-jun knockdown could partially block SOD mRNA level that might involve in the modulation of NPY gene expression. It was suggested that c-fos/c-jun signaling might involve in the central regulation of AMPH-mediated feeding suppression via the modulation of NPY gene expression.
Hsieh
Yih-Shou
YS
Institute of Biochemistry, Chung Shan Medical University, Taichung, Taiwan, R.O.C.
Yang
Shun-Fa
SF
Chiou
Hui-Ling
HL
Kuo
Dong-Yih
DY
D000661:Amphetamine / Q000494:pharmacology*; D000818:Animals; D001067:Appetite Depressants / Q000494:pharmacology*; D004591:Electrophoresis, Polyacrylamide Gel; D005786:Gene Expression Regulation / Q000187:drug effects; D016762:Genes, fos / Q000502:physiology*; D016758:Genes, jun / Q000502:physiology*; D007031:Hypothalamus / Q000201:enzymology / Q000378:metabolism*; D007276:Injections, Intraventricular; D008297:Male; D009478:Neuropeptide Y / Q000096:biosynthesis* / Q000235:genetics*; D020319:Oligodeoxyribonucleotides, Antisense / Q000008:administration & dosage / Q000494:pharmacology; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects; D013482:Superoxide Dismutase / Q000096:biosynthesis* / Q000235:genetics*; D000072105:Superoxide Dismutase-1
D001067:Appetite Depressants; D009478:Neuropeptide Y; D020319:Oligodeoxyribonucleotides, Antisense; D012333:RNA, Messenger; D000661:Amphetamine; C000606292:Sod1 protein, rat; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1