Involvement of nuclear factor-κB and apoptosis signal-regulating kinase 1 in G-protein-coupled receptor agonist-induced cardiomyocyte hypertrophy

被引:319
作者
Hirotani, S
Otsu, K
Nishida, K
Higuchi, Y
Morita, T
Nakayama, H
Yamaguchi, O
Mano, T
Matsumura, Y
Ueno, H
Tada, M
Hori, M
机构
[1] Osaka Univ, Grad Sch Med, Dept Pathophysiol, Suita, Osaka 5650871, Japan
[2] Osaka Univ, Grad Sch Med, Dept Internal Med & Therapeut, Suita, Osaka, Japan
[3] Osaka Univ, Grad Sch Med, Dept Med Informat Sci, Suita, Osaka, Japan
[4] Univ Occupat & Environm Hlth, Sch Med, Dept Biochem & Mol Pathophysiol, Kitakyushu, Fukuoka, Japan
关键词
hypertrophy; myocytes; signal transduction; free radicals;
D O I
10.1161/hc0402.102863
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Background-Recently, reactive oxygen species (ROS) have emerged as important molecules in cardiac hypertrophy. However, the ROS-dependent signal transduction mechanism remains to be elucidated. In this study, we examined the role of an ROS-sensitive transcriptional factor, NF-kappaB, and a mitogen-activated protein kinase kinase kinase, apoptosis signal-regulating kinase I (ASK1), in G-protein-coupled receptor (GPCR) agonist (angiotensin 11, endothelin-1, phenylephrine)-induced cardiac hypertrophy in isolated rat neonatal cardiomyocytes. Methods and Results-Using an ROS-sensitive fluorescent dye, we observed an increase in fluorescence signal on addition of the GPCR agonists. The GPCR agonists induced NF-kappaB activation. Antioxidants such as N-acetyl cysteine, N-mercaptopropionyl glycine, and vitamin E attenuated the NF-kappaB activation. Infection of cardiomyocytes with an adenovirus expressing a degradation-resistant mutant Of IkappaBalpha led to suppression of the hypertrophic responses. The GPCR agonists rapidly and transiently activated ASK1 in a dose-dependent manner. Infection of an adenovirus expressing a dominant-negative ASK1 attenuated the GPCR agonist-induced NF-kappaB activation and cardiac hypertrophy. Overexpression of a constitutively active mutant of ASK1 led to NF-kappaB activation and cardiac hypertrophy. Activated ASK1-induced hypertrophy was abolished by inhibition of NF-kappaB activation. Conclusions-These data indicate that GPCR agonist-induced cardiac hypertrophy is mediated through NF-kappaB activation via the generation of ROS. ASK1 is involved in GPCR agonist-induced NF-kappaB activation and resulting hypertrophy.
引用
收藏
页码:509 / 515
页数:7
相关论文
共 19 条
[1]   Role of redox potential and reactive oxygen species in stress signaling [J].
Adler, V ;
Yin, ZM ;
Tew, KD ;
Ronai, Z .
ONCOGENE, 1999, 18 (45) :6104-6111
[2]   ANGIOTENSIN-II STIMULATES NADH AND NADPH OXIDASE ACTIVITY IN CULTURED VASCULAR SMOOTH-MUSCLE CELLS [J].
GRIENDLING, KK ;
MINIERI, CA ;
OLLERENSHAW, JD ;
ALEXANDER, RW .
CIRCULATION RESEARCH, 1994, 74 (06) :1141-1148
[3]   MEK kinase is involved in tumor necrosis factor alpha-induced NF-kappa B activation and degradation of I kappa B-alpha [J].
Hirano, M ;
Osada, S ;
Aoki, T ;
Hirai, S ;
Hosaka, M ;
Inoue, J ;
Ohno, S .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1996, 271 (22) :13234-13238
[4]   Induction of apoptosis by ASK1, a mammalian MAPKKK that activates SAPK/JNK and p38 signaling pathways [J].
Ichijo, H ;
Nishida, E ;
Irie, K ;
tenDijke, P ;
Saitoh, M ;
Moriguchi, T ;
Takagi, M ;
Matsumoto, K ;
Miyazono, K ;
Gotoh, Y .
SCIENCE, 1997, 275 (5296) :90-94
[5]   THYROID-HORMONE ENHANCES CA2+ PUMPING ACTIVITY OF THE CARDIAC SARCOPLASMIC-RETICULUM BY INCREASING CA2+ ATPASE AND DECREASING PHOSPHOLAMBAN EXPRESSION [J].
KIMURA, Y ;
OTSU, K ;
NISHIDA, K ;
KUZUYA, T ;
TADA, M .
JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY, 1994, 26 (09) :1145-1154
[6]   Mechanical strain activates BNP gene transcription through a p38/NF-κB-dependent mechanism [J].
Liang, FQ ;
Gardner, DG .
JOURNAL OF CLINICAL INVESTIGATION, 1999, 104 (11) :1603-1612
[7]   A calcineurin-dependent transcriptional pathway for cardiac hypertrophy [J].
Molkentin, JD ;
Lu, JR ;
Antos, CL ;
Markham, B ;
Richardson, J ;
Robbins, J ;
Grant, SR ;
Olson, EN .
CELL, 1998, 93 (02) :215-228
[8]   Inhibitory effects of antioxidants on neonatal rat cardiac myocyte hypertrophy induced by tumor necrosis factor-a and angiotensin II [J].
Nakamura, K ;
Fushimi, K ;
Kouchi, H ;
Mihara, K ;
Miyazaki, M ;
Ohe, T ;
Namba, M .
CIRCULATION, 1998, 98 (08) :794-799
[9]   Opposing effects of Jun kinase and p38 mitogen-activated protein kinases on cardiomyocyte hypertrophy [J].
Nemoto, S ;
Sheng, ZL ;
Lin, AN .
MOLECULAR AND CELLULAR BIOLOGY, 1998, 18 (06) :3518-3526
[10]   The kinase TAK1 can activate the NIK-IκB as well as the MAP kinase cascade in the IL-1 signalling pathway [J].
Ninomiya-Tsuji, J ;
Kishimoto, K ;
Hiyama, A ;
Inoue, J ;
Cao, ZD ;
Matsumoto, K .
NATURE, 1999, 398 (6724) :252-256