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Distribution of neuroendocrine regulatory peptide-1 and -2, and proteolytic processing of their precursor VGF protein in the rat.
Distribution of neuroendocrine regulatory peptide-1 and -2, and proteolytic processing of their precursor VGF protein in the rat.
- Source :
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Journal of neurochemistry [J Neurochem] 2010 Aug; Vol. 114 (4), pp. 1097-106. Date of Electronic Publication: 2010 May 26. - Publication Year :
- 2010
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Abstract
- Neuroendocrine regulatory peptide (NERP)-1 and NERP-2 are biologically active peptides recently discovered by peptidomic analysis. NERPs are processed out from the 594-residue VGF protein which contains many prohormone convertase cleavage motifs. VGF-deficient mice exhibit a hypermetabolic and infertile phenotype, for which VGF protein-derived peptides including NERPs are presumably responsible. To provide a solid basis for elucidating physiological roles of NERPs, we investigated rat VGF protein processing by chromatographic and mass spectrometric analysis, and immunoblotting, using antibodies against NERPs and the VGF protein C-terminus (VGF-C). Cellular and tissue distribution of immunoreactive (ir) NERPs were also analyzed in the rat. Both ir-NERP-1 and ir-NERP-2, which occur abundantly in the CNS and pituitary, moderately in the gastrointestinal (GI) tract, were mainly localized in neuronal structures. Major endogenous forms of ir-NERPs in the brain and GI tract were identified as NERP-1, NERP-2, and big NERP-2 (NERP-1 + NERP-2), with NERP-1 and big NERP-2 being predominant. Regarding ir-VGF-C peptides, VGF[588-617], VGF[556-617], and VGF[509-617] were found to be major forms. Immunoblotting with the NERP-2 and VGF-C antibodies revealed processing intermediates of 10-37 kDa. Taken together, we deduce that VGF protein is primarily cleaved at 10 sites through the processing pathway common to the brain and GI tract.
- Subjects :
- Animals
Gastrointestinal Tract cytology
Nerve Tissue Proteins chemistry
Neuropeptides chemistry
Peptides chemistry
Peptides metabolism
Pituitary Gland chemistry
Pituitary Gland cytology
Pituitary Gland metabolism
Protein Precursors chemistry
Rats
Rats, Sprague-Dawley
Rats, Wistar
Tissue Distribution physiology
Brain Chemistry physiology
Gastrointestinal Tract metabolism
Nerve Tissue Proteins metabolism
Neuropeptides metabolism
Protein Precursors metabolism
Protein Processing, Post-Translational
Subjects
Details
- Language :
- English
- ISSN :
- 1471-4159
- Volume :
- 114
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- Journal of neurochemistry
- Publication Type :
- Academic Journal
- Accession number :
- 20524965
- Full Text :
- https://doi.org/10.1111/j.1471-4159.2010.06827.x