Stretch-induced hypertrophic growth of cardiocytes and processing of brain-type natriuretic peptide are controlled by proprotein-processing endoprotease furin.

Abstract

When hypertrophic growth is induced in neonatal rat cardiocytes by stretching, the cardiocytes express high levels of brain-type natriuretic peptide (BNP) and the proprotein-processing enzyme furin. A BNP precursor, gammaBNP, possesses a furin-cleavable Arg-X-X-Arg motif, which is cleaved when gammaBNP is processed to form BNP-45. The Arg-X-X-Arg motif is found in many precursors of growth factors and growth-related proteins. To determine if furin converts gammaBNP to BNP-45 as well as other unidentified growth-promoting protein precursors to their active form that may induce hypertrophic growth in cardiocytes, we used two protease inhibitor systems, synthetic peptidyl chloromethyl ketones (CMK) (dec-Arg-Val-Lys-Arg-CMK and dec-Phe-Ala-Lys-Arg-CMK; where dec is decanoyl) and vaccinia vector-integrated native and variant alpha1-antitrypsins. The furin-specific inhibitors, dec-Arg-Val-Lys-Arg-CMK and variant alpha1-antitrypsin with the inhibitory determinant Arg-X-X-Arg, suppressed the stretch-induced hypertrophic growth of cardiocytes as well as the processing of gammaBNP to BNP-45. The other serine protease inhibitors and variant alpha1-antitrypsin against elastase, or thrombin, however, neither suppressed the hypertrophic growth nor prevented the processing of gammaBNP to BNP-45. Thus, we suggest that furin catalyzes the conversion of gammaBNP to BNP-45 as well as growth-promoting proproteins to their active form, which might induce hypertrophic growth in cardiocytes.

• Authors: Y Sawada, M Suda, H Yokoyama, T Kanda, T Sakamaki, S Tanaka, R Nagai, S Abe, T Takeuchi
• Journal: The Journal of biological chemistry (J Biol Chem) Vol. 272 Issue 33 Pg. 20545-54 (Aug 15 1997) ISSN: 0021-9258 [Print] United States
• PMID: 9252368 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Nerve Tissue Proteins
• Protein Precursors
• Natriuretic Peptide, Brain
• Subtilisins
• Furin

Topics

• Animals
• Cardiomegaly (etiology)
• Cells, Cultured
• Furin
• Natriuretic Peptide, Brain
• Nerve Tissue Proteins (metabolism)
• Protein Precursors (metabolism)
• Rats
• Rats, Wistar
• Subtilisins (physiology)