Angiotensin II induces p27(Kip1) expression in renal tubules in vivo: roleof reactive oxygen species

Citation
G. Wolf et al., Angiotensin II induces p27(Kip1) expression in renal tubules in vivo: roleof reactive oxygen species, J MOL MED-J, 79(7), 2001, pp. 382-389
Citations number
28
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Research/Laboratory Medicine & Medical Tecnology","Medical Research General Topics
Journal title
JOURNAL OF MOLECULAR MEDICINE-JMM
ISSN journal
0946-2716 → ACNP
Volume
79
Issue
7
Year of publication
2001
Pages
382 - 389
Database
ISI
SICI code
0946-2716(200107)79:7<382:AIIPEI>2.0.ZU;2-A
Abstract
Previous studies have demonstrated that angiotensin II (ANG II) mediates ce ll cycle arrest of cultured renal tubular cells by induction of p27(Kip1). an inhibitor of cyclin-dependent kinases. However, it is not known whether ANG II exerts similar effects in vivo. Infusion of ANG II into naive rats f or 7 days increased formation of reactive oxygen species in tubular cells o f the kidney. Furthermore, ANG II infusion stimulated protein expression of p27(Kip1) as detected by western blotting of tubular lysates and immunohis tochemistry. Infusion of ANG II reduced tubular proliferation as detected b y proliferating-cell nuclear antigen (PCNA) immunohistochemistry. The incre ase in p27(Kip1) expression was not due to an increase in mRNA. Immunopreci pitation experiments revealed that the increased p27(Kip1) protein associat es with cyclin-dependent kinase 2. Coadministration of the radical scavenge r dimethylthiourea abolished this ANG II mediated p27(Kip1) expression with out reducing systemic blood pressure. Furthermore, dimethylthiourea infusio n attenuates the ANG II mediated G(1)-phase arrest of tubular cells. Howeve r, infusion of norepinephrine did not induce reactive oxygen species or p27 (Kip1) expression, despite a significant increase in blood pressure. Thus A NG II induces p27(Kip1) expression in renal tubular cells in vivo. This eff ect is mediated by reactive oxygen species. Since tubular hypertrophy depen ds on G(1)-phase arrest and may promote subsequent development of interstit ial fibrosis, administering oxygen radical scavenger may be a therapeutic t ool to counteract ANG II dependent remodeling of renal tubular cells.