ProSAAS Processing in Mouse Brain and Pituitary

Nino Mzhavia, Yemiliya Berman, Fa Yun Che, Lloyd D. Fricker, Lakshmi A. Devi

Research output: Contribution to journalArticle

41 Citations (Scopus)

Abstract

ProSAAS is a newly discovered protein with a neuroendocrine distribution generally similar to that of prohormone convertase 1 (PC1), a peptide-processing endopeptidase. Several proSAAS-derived peptides were previously identified in the brain and pituitary of the Cpe fat/Cpefat mouse based on the accumulation of C-terminally extended peptides due to the absence of enzymatically active carboxypeptidase E, a peptide-processing exopeptidase. In the present study, antisera against different regions of proSAAS were used to develop radioimmunoassays and examine the processing profile of proSAAS in wild type and Cpefat/Cpefat mouse tissues following gel filtration and reverse phase high performance liquid chromatography. In wild type mouse brain and pituitary, the majority of proSAAS is processed into smaller peptides. These proSAAS-derived peptides elute from the reverse-phase column in the same positions as synthetic peptides that correspond to little SAAS, PEN, and big LEN. Mass spectrometry revealed the presence of peptides with the expected molecular masses of little SAAS and big LEN in the fractions containing immunoreactive peptides. The processing of proSAAS is slightly impaired in Cpefat/Cpefat mice, relative to wild-type mice, leading to the accumulation of partially processed peptides. One of these peptides, the C-terminally extended form of PEN, is known to inhibit PC1 activity and this could account for the reduction in enzymatically active PC1 seen in Cpe fat/Cpefat mice. The observation that little SAAS and big LEN are the major forms of these peptides produced in mouse brain and pituitary raises the possibility that these peptides function as neurotransmitters or hormones.

Original languageEnglish (US)
Pages (from-to)6207-6213
Number of pages7
JournalJournal of Biological Chemistry
Volume276
Issue number9
DOIs
StatePublished - Mar 2 2001

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Brain
Peptides
Processing
Proprotein Convertase 1
Carboxypeptidase H
Fats
Exopeptidases
Endopeptidases
High performance liquid chromatography
Molecular mass
Reverse-Phase Chromatography
Radioimmunoassay
Gel Chromatography
Mass spectrometry
Neurotransmitter Agents
Immune Sera
Mass Spectrometry
Gels
High Pressure Liquid Chromatography
Hormones

ASJC Scopus subject areas

  • Biochemistry

Cite this

ProSAAS Processing in Mouse Brain and Pituitary. / Mzhavia, Nino; Berman, Yemiliya; Che, Fa Yun; Fricker, Lloyd D.; Devi, Lakshmi A.

In: Journal of Biological Chemistry, Vol. 276, No. 9, 02.03.2001, p. 6207-6213.

Research output: Contribution to journalArticle

Mzhavia, N, Berman, Y, Che, FY, Fricker, LD & Devi, LA 2001, 'ProSAAS Processing in Mouse Brain and Pituitary', Journal of Biological Chemistry, vol. 276, no. 9, pp. 6207-6213. https://doi.org/10.1074/jbc.M009067200
Mzhavia, Nino ; Berman, Yemiliya ; Che, Fa Yun ; Fricker, Lloyd D. ; Devi, Lakshmi A. / ProSAAS Processing in Mouse Brain and Pituitary. In: Journal of Biological Chemistry. 2001 ; Vol. 276, No. 9. pp. 6207-6213.
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