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
相关论文
共 42 条
[11]   Angiotensin II-mediated expression of p27Kip1 induction of cellular hypertrophy in renal tubular cells depend on the generation of oxygen radicals [J].
Hannken, T ;
Schroeder, R ;
Stahl, RAK ;
Wolf, G .
KIDNEY INTERNATIONAL, 1998, 54 (06) :1923-1933
[12]   ATRIAL-NATRIURETIC-PEPTIDE INHIBITS ANGIOTENSIN-STIMULATED PROXIMAL TUBULAR SODIUM AND WATER REABSORPTION [J].
HARRIS, PJ ;
THOMAS, D ;
MORGAN, TO .
NATURE, 1987, 326 (6114) :697-698
[13]  
HARRIS PJ, 1990, KIDNEY INT, V38, pS87
[14]   REGULATION OF S6 KINASE-ACTIVITY IN RENAL PROXIMAL TUBULE [J].
HARRIS, RC .
AMERICAN JOURNAL OF PHYSIOLOGY, 1992, 263 (01) :F127-F134
[15]   Downregulation of angiotensin II type 1 receptor gene transcription by nitric oxide [J].
Ichiki, T ;
Usui, M ;
Kato, M ;
Funakoshi, Y ;
Ito, K ;
Egashira, K ;
Takeshita, A .
HYPERTENSION, 1998, 31 (01) :342-348
[16]   ATRIAL NATRIURETIC POLYPEPTIDE INHIBITS HYPERTROPHY OF VASCULAR SMOOTH-MUSCLE CELLS [J].
ITOH, H ;
PRATT, RE ;
DZAU, VJ .
JOURNAL OF CLINICAL INVESTIGATION, 1990, 86 (05) :1690-1697
[17]   INTERACTION OF ATRIAL NATRIURETIC POLYPEPTIDE AND ANGIOTENSIN-II ON PROTOONCOGENE EXPRESSION AND VASCULAR CELL-GROWTH [J].
ITOH, H ;
PRATT, RE ;
DZAU, VJ .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 1991, 176 (03) :1601-1609
[18]   A NOVEL BIOLOGICAL EFFECT OF ATRIAL NATRIURETIC HORMONE - INHIBITION OF MESANGIAL CELL MITOGENESIS [J].
JOHNSON, A ;
LERMIOGLU, F ;
GARG, UC ;
MORGANBOYD, R ;
HASSID, A .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 1988, 152 (02) :893-897
[19]  
KATFUCHI T, 1992, J BIOL CHEM, V267, P7624
[20]  
Levin ER, 1998, NEW ENGL J MED, V339, P321