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



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



Journal of Biological Chemistry 272(33): 20545-20554



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, gamma-BNP, possesses a furin-cleavable Arg-X-X-Arg motif, which is cleaved when gamma-BNP is processed to form BNP45. The Arg-X-X-Arg motif is found in many precursors of growth factors and growth-related proteins. To determine if ALPHA-n converts gamma-BNP 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) (decArg-Val-Lys-Arg-CMK and dec-Phe-Ala-Lys-Arg-CMK; where dec is decanoyl) and vaccinia vector-integrated native and variant alpha-1-antitrypsins. The furin-specific inhibitors, dec-Arg-Val-Lys-Arg-CMK and variant alpha-1-antitrypsin with the inhibitory determinant Arg-X-X-Arg, suppressed the stretch-induced hypertrophic growth of cardiocytes as well as the processing of gamma-BNP to BNP-45. The other serine protease inhibitors and variant alpha-1-antitrypsin against elastase, or thrombin, however, neither suppressed the hypertrophic growth nor prevented the processing of gamma-BNP to BNP-45. Thus, we suggest that furin catalyzes the conversion of gamma-BNP to BNP-45 as well as growth-promoting proproteins to their active form, which might induce hypertrophic growth in cardiocytes.

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Accession: 009462785

Download citation: RISBibTeXText

PMID: 9252368

DOI: 10.1074/jbc.272.33.20545


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