| Full text | |
| Author(s): |
Barauna, Valerio Garrone
[1]
;
Gastalho Campos, Luciene Cristina
[1]
;
Miyakawa, Ayumi Aurea
[1]
;
Krieger, Jose Eduardo
[1]
Total Authors: 4
|
| Affiliation: | [1] Univ Sao Paulo, Sch Med, Heart Inst InCor, Lab Genet & Mol Cardiol, Sao Paulo - Brazil
Total Affiliations: 1
|
| Document type: | Journal article |
| Source: | PLoS One; v. 6, n. 8 AUG 25 2011. |
| Web of Science Citations: | 16 |
| Abstract | |
Objectives: We tested whether angiotensin converting enzyme (ACE) and phosphorylation of Ser(1270) are involved in shear-stress (SS)-induced downregulation of the enzyme. Methods and Results: Western blotting analysis showed that SS (18 h, 15 dyn/cm(2)) decreases ACE expression and phosphorylation as well as p-JNK inhibition in human primary endothelial cells (EC). CHO cells expressing wild-type ACE (wt-ACE) also displayed SS-induced decrease in ACE and p-JNK. Moreover, SS decreased ACE promoter activity in wt-ACE, but had no effect in wild type CHO or CHO expressing ACE without either the extra-or the intracellular domains, and decreased less in CHO expressing a mutated ACE at Ser(1270) compared to wt-ACE (13 vs. 40%, respectively). The JNK inhibitor (SP600125, 18 h), in absence of SS, also decreased ACE promoter activity in wt-ACE. Finally, SS-induced inhibition of ACE expression and phosphorylation in EC was counteracted by simultaneous exposure to an ACE inhibitor. Conclusions: ACE displays a key role on its own downregulation in response to SS. This response requires both the extra- and the intracellular domains and ACE Ser(1270), consistent with the idea that the extracellular domain behaves as a mechanosensor while the cytoplasmic domain elicits the downstream intracellular signaling by phosphorylation on Ser(1270). (AU) | |
| FAPESP's process: | 01/00009-0 - An integrated approach for the dissection of primary hypertension: molecular and functional characterization of the cardiovascular system |
| Grantee: | Eduardo Moacyr Krieger |
| Support Opportunities: | Research Projects - Thematic Grants |