Neuropeptide processing profile in mice lacking prohormone convertase-1

Hui Pan, Daniela Nanno, Fa Yun Che, Xiaorong Zhu, Stephen R. Salton, Donald F. Steiner, Lloyd D. Fricker, Lakshmi A. Devi

Research output: Contribution to journalArticle

62 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)4939-4948
Number of pages10
JournalBiochemistry
Volume44
Issue number12
DOIs
StatePublished - Mar 29 2005

Fingerprint

Proprotein Convertase 1
Neuropeptides
Knockout Mice
Peptides
Chromogranin B
Processing
Chromogranin A
Brain
Pro-Opiomelanocortin
Secretogranin II
Methionine Enkephalin
Oxytocin
Radioimmunoassay
Mass Spectrometry
Molecular Weight
Mass spectrometry
Molecular weight

ASJC Scopus subject areas

  • Biochemistry

Cite this

Pan, H., Nanno, D., Che, F. Y., Zhu, X., Salton, S. R., Steiner, D. F., ... Devi, L. A. (2005). Neuropeptide processing profile in mice lacking prohormone convertase-1. Biochemistry, 44(12), 4939-4948. https://doi.org/10.1021/bi047852m

Neuropeptide processing profile in mice lacking prohormone convertase-1. / Pan, Hui; Nanno, Daniela; Che, Fa Yun; Zhu, Xiaorong; Salton, Stephen R.; Steiner, Donald F.; Fricker, Lloyd D.; Devi, Lakshmi A.

In: Biochemistry, Vol. 44, No. 12, 29.03.2005, p. 4939-4948.

Research output: Contribution to journalArticle

Pan, H, Nanno, D, Che, FY, Zhu, X, Salton, SR, Steiner, DF, Fricker, LD & Devi, LA 2005, 'Neuropeptide processing profile in mice lacking prohormone convertase-1', Biochemistry, vol. 44, no. 12, pp. 4939-4948. https://doi.org/10.1021/bi047852m
Pan H, Nanno D, Che FY, Zhu X, Salton SR, Steiner DF et al. Neuropeptide processing profile in mice lacking prohormone convertase-1. Biochemistry. 2005 Mar 29;44(12):4939-4948. https://doi.org/10.1021/bi047852m
Pan, Hui ; Nanno, Daniela ; Che, Fa Yun ; Zhu, Xiaorong ; Salton, Stephen R. ; Steiner, Donald F. ; Fricker, Lloyd D. ; Devi, Lakshmi A. / Neuropeptide processing profile in mice lacking prohormone convertase-1. In: Biochemistry. 2005 ; Vol. 44, No. 12. pp. 4939-4948.
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