title: Human pro-B-type natriuretic peptide is processed in the circulation in a rat model.
abstract: BACKGROUND
  The appearance of B-type natriuretic peptide (BNP) in the blood is ultimately caused by proteolytic processing of its precursor, proBNP. The mechanisms leading to the high plasma concentration of unprocessed proBNP are still poorly understood. The goals of the present study were to examine whether processing of proBNP takes place in the circulation and to evaluate the clearance rate of proBNP and proBNP-derived peptides.
  
  
  METHODS
  We studied the processing of human proBNP in the circulation and the clearance rate of proBNP and proBNP-derived peptides (BNP and N-terminal fragment of proBNP, NT-proBNP) in rats by injecting the corresponding peptides and analyzing immunoreactivity at specific time points. Glycosylated and nonglycosylated proBNP and NT-proBNP were used in the experiments. We applied immunoassays, gel filtration, and mass spectrometry (MS) techniques to analyze the circulation-mediated processing of proBNP.
  
  
  RESULTS
  ProBNP was effectively processed in the circulation into BNP (1-32) and various truncated BNP forms as confirmed by gel filtration and MS analysis. Glycosylation of proBNP close to the cleavage-site region suppressed its processing in the circulation. The terminal half-life for human glycosylated proBNP was 9.0 (0.5) min compared with 6.4 (0.5) min for BNP. For NT-proBNP, the terminal half-lives were 15.7 (1.4) min and 15.5 (1.3) min for glycosylated and nonglycosylated forms, respectively.
  
  
  CONCLUSIONS
  In rats, processing of human proBNP to active BNP occurs in the circulation. The clearance rate of proBNP is quite similar to that of BNP. These observations suggest that peripheral proBNP processing may be an important regulatory step rather than mere degradation.
authors.affiliation: HyTest Ltd., Turku, Finland. alexander.semenov@hytest.fi
authors.forename: Alexander G
authors.initials: AG
authors.lastname: Semenov
authors.forename: Karina R
authors.initials: KR
authors.lastname: Seferian
authors.forename: Natalia N
authors.initials: NN
authors.lastname: Tamm
authors.forename: Marina M
authors.initials: MM
authors.lastname: Artem'eva
authors.forename: Alexander B
authors.initials: AB
authors.lastname: Postnikov
authors.forename: Anastasiya V
authors.initials: AV
authors.lastname: Bereznikova
authors.forename: Andrey N
authors.initials: AN
authors.lastname: Kara
authors.forename: Natalia A
authors.initials: NA
authors.lastname: Medvedeva
authors.forename: Alexey G
authors.initials: AG
authors.lastname: Katrukha
mesh_terms: D000818:Animals; D001775:Blood Circulation; D006031:Glycosylation; D006207:Half-Life; D006801:Humans; D008297:Male; D020097:Natriuretic Peptide, Brain / Q000097:blood*; D010446:Peptide Fragments / Q000097:blood*; D011498:Protein Precursors / Q000097:blood*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D010446:Peptide Fragments; D011498:Protein Precursors; C109794:pro-brain natriuretic peptide (1-76); D020097:Natriuretic Peptide, Brain