title: Neuropeptide processing profile in mice lacking prohormone convertase-1.
abstract: Prohormone convertase 1 (PC1; also known as PC3) is believed to be responsible for the processing of many neuropeptide precursors. To look at the role PC1 plays in neuropeptide processing in brain and pituitary, we used radioimmunoassays (RIA) as well as quantitative peptidomic methods and examined changes in the levels of multiple neuropeptide products in PC1 knockout (KO) mice. The processing of proenkephalin was impaired in PC1 KO mouse brains with a decrease in the level of Met-Enkephalin immunoreactivity (ir-Met-Enk) and an accumulation of higher molecular weight processing intermediates containing ir-Met-Enk. Processing of the neuropeptide precursor VGF was also affected in PC1 KO mouse brains with a decrease in the level of an endogenous 3 kDa C-terminal peptide. In contrast, the processing of proSAAS into PEN was not altered in PC1 KO mouse brains. Quantitative mass spectrometry was used to analyze a number of peptides derived from proopiomelanocortin (POMC), provasopressin, prooxytocin, chromogranin A, chromogranin B, and secretogranin II. Among them, the levels of oxytocin and peptides derived from chromogranin A and B dramatically decreased in the PC1 KO mouse pituitaries, while the levels of peptides derived from proopiomelanocortin and provasopressin did not show substantial changes. In conclusion, these results support the notion that PC1 plays a key role in the processing of multiple neuroendocrine peptide precursors and also reveal the presence of a redundant system in the processing of a number of physiologically important bioactive peptides.
authors.affiliation: Department of Pharmacology and Biological Chemistry, Mount Sinai School of Medicine, One Gustave L. Levy Place, New York 10029, USA.
authors.forename: Hui
authors.initials: H
authors.lastname: Pan
authors.forename: Daniela
authors.initials: D
authors.lastname: Nanno
authors.forename: Fa-Yun
authors.initials: FY
authors.lastname: Che
authors.forename: Xiaorong
authors.initials: X
authors.lastname: Zhu
authors.forename: Stephen R
authors.initials: SR
authors.lastname: Salton
authors.forename: Donald F
authors.initials: DF
authors.lastname: Steiner
authors.forename: Lloyd D
authors.initials: LD
authors.lastname: Fricker
authors.forename: Lakshmi A
authors.initials: LA
authors.lastname: Devi
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D004745:Enkephalins / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins / Q000737:chemistry / Q000378:metabolism; D009479:Neuropeptides / Q000737:chemistry* / Q000378:metabolism* / Q000502:physiology; D010902:Pituitary Gland / Q000737:chemistry / Q000378:metabolism; D045664:Proprotein Convertase 1 / Q000172:deficiency* / Q000235:genetics* / Q000502:physiology; D011498:Protein Precursors / Q000737:chemistry* / Q000378:metabolism*; D011499:Protein Processing, Post-Translational / Q000235:genetics*; D011506:Proteins / Q000737:chemistry / Q000378:metabolism; D040901:Proteomics / Q000379:methods; D011863:Radioimmunoassay / Q000379:methods
chemical_list: D004745:Enkephalins; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins; D009479:Neuropeptides; C112832:Pcsk1n protein, mouse; D011498:Protein Precursors; D011506:Proteins; C512697:Vgf protein, mouse; C029992:proenkephalin; D045664:Proprotein Convertase 1