| Full text | |
| Author(s): Show less - |
Guerreiro, Juliano R.
[1]
;
Lameu, Claudiana
[1]
;
Oliveira, Eduardo F.
[2]
;
Klitzke, Clecio F.
;
Melo, Robson L.
;
Linares, Edlaine
[1]
;
Augusto, Ohara
[1]
;
Fox, Jay W.
[3]
;
Lebrun, Ivo
[4]
;
Serrano, Solange M. T.
[5]
;
Camargo, Antonio C. M.
Total Authors: 11
|
| Affiliation: | [1] Univ Sao Paulo, Inst Quim, Dept Bioquim, BR-05513970 Sao Paulo - Brazil
[2] Univ Fed Sao Paulo, Dept Biol Mol, BR-04044020 Sao Paulo - Brazil
[3] Univ Virginia, Dept Microbiol, Charlottesville, VA 22908 - USA
[4] Inst Butantan, Lab Bioquim & Biofis, BR-05503900 Sao Paulo - Brazil
[5] Inst Butantan, Lab Especial Toxicol Aplicada, CAT CEPID, BR-05503900 Sao Paulo - Brazil
Total Affiliations: 5
|
| Document type: | Journal article |
| Source: | Journal of Biological Chemistry; v. 284, n. 30, p. 20022-20033, JUL 24 2009. |
| Web of Science Citations: | 39 |
| Abstract | |
Bj-BPP-10c is a bioactive proline-rich decapeptide, part of the C-type natriuretic peptide precursor, expressed in the brain and in the venom gland of Bothrops jararaca. We recently showed that Bj-BPP-10c displays a strong, sustained anti-hypertensive effect in spontaneous hypertensive rats (SHR), without causing any effect in normotensive rats, by a pharmacological effect independent of angiotensin-converting enzyme inhibition. Therefore, we hypothesized that another mechanism should be involved in the peptide activity. Here we used affinity chromatography to search for kidney cytosolic proteins with affinity for Bj-BPP-10c and demonstrate that argininosuccinate synthetase (AsS) is the major protein binding to the peptide. More importantly, this interaction activates the catalytic activity of AsS in a dose-dependent manner. AsS is recognized as an important player of the citrulline-NO cycle that represents a potential limiting step in NO synthesis. Accordingly, the functional interaction of Bj-BPP-10c and AsS was evidenced by the following effects promoted by the peptide: (i) increase of NO metabolite production in human umbilical vein endothelial cell culture and of arginine in human embryonic kidney cells and (ii) increase of arginine plasma concentration in SHR. Moreover, alpha-methyl-DL-aspartic acid, a specific AsS inhibitor, significantly reduced the anti-hypertensive activity of Bj-BPP-10c in SHR. Taken together, these results suggest that AsS plays a role in the anti-hypertensive action of Bj-BPP-10c. Therefore, we propose the activation of AsS as a new mechanism for the anti-hypertensive effect of Bj-BPP-10c in SHR and AsS as a novel target for the therapy of hypertension-related diseases. (AU) | |
| FAPESP's process: | 98/14307-9 - Center for Applied Toxinology |
| Grantee: | Hugo Aguirre Armelin |
| Support Opportunities: | Research Grants - Research, Innovation and Dissemination Centers - RIDC |