Interrupting activator protein-1 signaling in conscious rats can modify neuropeptide Y gene expression and feeding behavior of phenylpropanolamine

Authors: Hsieh, Yih-Shou¹; Yang, Shun-Fa²; Chu, Shu-Chen³; Kuo, Dong-Yih⁴

Source: Journal of Neurochemistry, Volume 104, Number 1, January 2008 , pp. 50-61(12)

Publisher: Wiley-Blackwell

Abstract:

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.

Keywords: feeding behavior; immediate early gene; neuropeptide Y; phenylpropanolamine; superoxide dismutase

Document Type: Research article

DOI: http://dx.doi.org/10.1111/j.1471-4159.2007.04919.x

Affiliations: 1: Institute of Biochemistry, Chung Shan Medical University, Taichung City, Taiwan 2: Institute of Medicine, Chung Shan Medical University, Taichung City, Taiwan 3: Department of Food Science, Central Taiwan University of Science and Technology, Taichung City, Taiwan 4: Department of Physiology, Chung Shan Medical University, Taichung City, Taiwan

Publication date: 2008-01-01

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