Processing of Pro–B-Type Natriuretic Peptide: Furin and Corin as Candidate Convertases

摘要: Background: B-type natriuretic peptide (BNP) and its N-terminal fragment (NT-proBNP) are the products of enzyme-mediated cleavage their precursor molecule, proBNP. The clinical significance proBNP-derived peptides as biomarkers heart failure has been explored thoroughly, whereas little is known about mechanisms proBNP processing. We investigated role 2 candidate convertases, furin corin, in human processing. Methods: measured expression HEK 293 furin-deficient LoVo cells. used a inhibitor furin-specific small interfering RNA (siRNA) to explore implication Recombinant proBNPs were incubated with cells transfected corin-expressing plasmid. applied mass spectrometry analyze furin- corin-mediated cleavage. Results: Reduction activity significantly impaired processing Furin-deficient unable process proBNP, coexpression resulted effective Mass spectrometric analysis revealed that furin-mediated BNP 1–32, led production 4–32. Some portion plasma patients was not glycosylated site region susceptible cleavage. Conclusions: Both corin involved pathway, giving rise distinct forms. presence unprocessed circulation could be cleaved by endogenous convertases should further for better understanding physiology.