Human Pro-B-Type Natriuretic Peptide Is Processed in the Circulation in a Rat Modelстатья
Статья опубликована в высокорейтинговом журнале
Информация о цитировании статьи получена из
Web of Science,
Scopus
Статья опубликована в журнале из списка Web of Science и/или Scopus
Дата последнего поиска статьи во внешних источниках: 18 июля 2013 г.
Аннотация: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 proBNPderived
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.