期刊
AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM
卷 304, 期 6, 页码 E640-E650出版社
AMER PHYSIOLOGICAL SOC
DOI: 10.1152/ajpendo.00448.2012
关键词
alpha-melanocyte-stimulating hormone; early growth response protein-1; neuropeptide Y; proopiomelanocortin; thyrotropin-releasing hormone
资金
- National Institute of Diabetes and Digestive and Kidney Diseases/National Institutes of Health Grant [R01 DK-085916-01]
- Initiative for Maximizing Student Diversity (IMSD), NIH
Cyr NE, Toorie AM, Steger JS, Sochat MM, Hyner S, Perello M, Stuart R, Nillni EA. Mechanisms by which the orexigen NPY regulates anorexigenic alpha-MSH and TRH. Am J Physiol Endocrinol Metab 67: E640-E650, 2013. First published January 15, 2013; doi:10.1152/ajpendo.00448.2012.-Protein posttranslational processing is a cellular mechanism fundamental to the generation of bioactive peptides, including the anorectic alpha-melanocyte-stimulating hormone (alpha-MSH) and thyrotropin-releasing hormone (TRH) peptides produced in the hypothalamic arcuate (ARC) and paraventricular (PVN) nuclei, respectively. Neuropeptide Y (NPY) promotes positive energy balance in part by suppressing alpha-MSH and TRH. The mechanism by which NPY regulates alpha-MSH output, however, is not well understood. Our results reveal that NPY inhibited the posttranslational processing of alpha-MSH's inactive precursor proopiomelanocortin (POMC) by decreasing the prohormone convertase-2 (PC2). We also found that early growth response protein-1 (Egr-1) and NPY-Y1 receptors mediated the NPY-induced decrease in PC2. NPY given intra-PVN also decreased PC2 in PVN samples, suggesting a reduction in PC2-mediated pro-TRH processing. In addition, NPY attenuated the alpha-MSH-induced increase in TRH production by two mechanisms. First, NPY decreased alpha-MSH-induced CREB phosphorylation, which normally enhances TRH transcription. Second, NPY decreased the amount of alpha-MSH in the PVN. Collectively, these results underscore the significance of the interaction between NPY and alpha-MSH in the central regulation of energy balance and indicate that posttranslational processing is a mechanism that plays a specific role in this interaction.
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