Atrial natriuretic peptide attenuates ANG II-induced hypertrophy of renal tubular cells

被引:28
作者
Hannken, T [1 ]
Schroeder, R [1 ]
Stahl, RAK [1 ]
Wolf, G [1 ]
机构
[1] Univ Hamburg, Hosp Eppendorf, Dept Med, Div Nephrol & Osteol, D-20246 Hamburg, Germany
关键词
tubular hypertrophy; cell cycle arrest; signal transduction; LLC-PK(1) cells; mitogen-activated protein kinases;
D O I
10.1152/ajprenal.2001.281.1.F81
中图分类号
Q4 [生理学];
学科分类号
071003 ;
摘要
ANG II arrests LLC-PK(1) cells in the G(1) phase of the cell cycle and induces hypertrophy, an effect mediated by induction of p27(Kip1). We studied whether atrial natriuretic peptide (ANP) may modulate ANG II-induced hypertrophy and p27(Kip1) expression in tubular LLC-PK(1) cells. ANP, through its fragments 3-28 and 4-27, prevented ANG II-induced cell cycle arrest. ANP inhibited >80% of ANG II-induced p27(Kip1) protein expression (Western blots). ANP stimulated expression of MKP-1, a phosphatase involved in dephosphorylation of p44/42 mitogen-activated protein (MAP) kinase, up to 12 h. ANP prevented the ANG II-mediated phosphorylation peak of MAP kinase after 12 h of stimulation. 8-Bromo-cGMP mimicked all the effects of ANP. Transfection with MKP-1 antisense, but not sense, oligonucleotides abolished the modifying role of ANP on ANG II-mediated cell cycle arrest. The effect of ANP on ANG II-mediated hypertrophy of LLC-PK(1) cells is regulated on the level of MAP kinase phosphorylation, a key step in the induction of p27(Kip1). Although ANP and ANG II both stimulate generation of reactive oxygen species, ANP additionally induces expression of MKP-1, leading to interference with ANG II-mediated MAP kinase phosphorylation.
引用
收藏
页码:F81 / F90
页数:10
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