Abstract
The peptide hormone apelin is translated as a 77-residue preproprotein, truncated to the 55-residue proapelin and, subsequently, to 13-36-residue bioactive isoforms named apelin-13 to -36. Proapelin is hypothesized to be cleaved to apelin-36 and then to the shorter isoforms. However, neither the mechanism of proapelin processing nor the endoproteases involved have been determined. We show direct cleavage of proapelin to apelin-13 by proprotein convertase subtilisin/kexin 3 (PCSK3, or furin) in vitro, with no production of longer isoforms. Conversely, neither PCSK1 nor PCSK7 has appreciable proapelin cleavage activity. Furthermore, we show that both proapelin and PCSK3 transcript expression levels are increased in adipose tissue with obesity and during adipogenesis, suggesting that PCSK3 is responsible for proapelin processing in adipose tissue.
| Original language | English |
|---|---|
| Pages (from-to) | 328-333 |
| Number of pages | 6 |
| Journal | FEBS Open Bio |
| Volume | 3 |
| DOIs | |
| Publication status | Published - 2013 |
Bibliographical note
Funding Information:This work was supported by a Canadian Institutes of Health Research (CIHR) Operating Grant (MOP-111138 to JKR); a Nova Scotia Health Research Foundation (NSHRF) Scotia Support Grant (to J . K.R.); a Natural Sciences and Engineering Research Council (NSERC) Discovery Grant (to X.Q.L.); and, the IWK Research Foundation (to Y.A.). Key equipment was provided by an NSERC Research Tools & Instruments Grant (J.K.R.), by Canadian Foundation for Innovation Leaders Opportunity Fund grants (to J.K.R. and Y.A.) and by a Dalhousie Medical Research Foundation grant (to J.K.R., X.Q.L. and Y.A.). J.K.R. is supported by a CIHR New Investigator Award and K.S. by an NSERC Canada Graduate Scholarship. We thank Bruce Stewart for technical support and Drs. David Langelaan and Jeffrey Gagnon for initial preproapelin vector design and helpful discussions.
ASJC Scopus Subject Areas
- General Biochemistry,Genetics and Molecular Biology
