NDLI: Inhibition of NF-κB Activity and Enhancement of Apoptosis by the Neuropeptide Calcitonin Gene-related Peptide

Content Provider	Journal of Biological Chemistry (JBC)
Author	Millet, Isabelle Phillips, Roderick J. Sherwin, Robert S. Ghosh, Sankar Voll, Reinhard E. Flavell, Richard A. Vignery, Agnès Rincón, Mercedes
Abstract	Calcitonin gene-related peptide (CGRP) is a neuropeptide produced by the central and peripheral nervous systems and by endocrine cells. CGRP exerts diverse biological effects on the cardiovascular, gastrointestinal, respiratory, central nervous and immune systems. Little is known, however, about the molecular mechanisms that mediate CGRP effects. Using the NFκB-luciferase reporter transgenic mice, here we show that CGRP selectively inhibits NF-κB-mediated transcription in thymocytes in vitro andin vivo. In contrast, CGRP does not affect transcription mediated by the AP-1 and NFAT transcription factors. CGRP inhibits the accumulation of NF-κB complexes in the nucleus by preventing phosphorylation and degradation of the NF-κB inhibitor IκB. Inhibition of NF-κB activity is associated with the induction of apoptosis by CGRP in thymocytes. Together these results demonstrate for the first time the selective implication of the NF-κB signaling pathway in the regulatory function of the neuropeptide CGRP. Our study suggests a potential molecular mechanism by which CGRP can induce cell death in thymocytes.
Related Links	http://www.jbc.org/content/275/20/15114.abstract
Ending Page	15121
Starting Page	15114
Page Count	8
File Format	HTM / HTML PDF
ISSN	00219258
Journal	Journal of Biological Chemistry (JBC)
Issue Number	20
Volume Number	275
DOI	10.1074/jbc.275.20.15114
e-ISSN	1083351X
Language	English
Publisher	American Society for Biochemistry and Molecular Biology
Publisher Date	2000-05-19
Access Restriction	Open
Subject Keyword	Calcitonin gene-related peptide (CGRP) Monoclonal antibody (mAb) Phorbol 12-myristate 13-acetate (PMA) Phosphate-buffered saline (PBS) Double stranded (ds) CAMP response element-binding protein (CREB) Electrophoretic mobility shift assay (EMSA) Tumor necrosis factor α (TNFα) Double positive (DP) Protein kinase A (PKA) MECHANISMS OF SIGNAL TRANSDUCTION
Content Type	Text
Resource Type	Article
Subject	Cell Biology Biochemistry Molecular Biology

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