Thyroid hormone-induced stimulation of the sarcoplasmic reticulum Ca2+ ATPase gene is inhibited by LIF and IL-6

被引:8
作者
Gloss, B [1 ]
Villegas, S [1 ]
Villarreal, FJ [1 ]
Moriscot, A [1 ]
Dillmann, WH [1 ]
机构
[1] Univ Calif San Diego, Dept Med, La Jolla, CA 92093 USA
来源
AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM | 2000年 / 278卷 / 04期
关键词
cardiac hypertrophy; heart failure; contraction; relaxation; cytokines;
D O I
10.1152/ajpendo.2000.278.4.E738
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
We investigated the effects of the leukemia inhibitory factor (LIF) and interleukin-6 (IL-6) on 3,3', 5-triiodo-L-thyronine, or thyroid hormone (T-3)-stimulated sarcoplasmic reticulum Ca2+ ATPase (SERCA2) gene expression on cultured neonatal rat cardiac myocytes. A reduction of Ta induced increases in SERCA2 mRNA levels after co-treatment with LIF or IL-6. To investigate for the molecular mechanism(s) responsible for the blunted gene expression, a 3.2-kb SERCA2 promoter construct containing a reporter gene was transfected into cardiac myocytes. T-3 treatment stimulated transcriptional activity twofold, whereas co-treatment with T-3 and either of the cytokines caused an inhibition of T-3-induced SERCA2 transcriptional activity. A T-3-responsive 0.6-kb SERCA2 construct also showed a similar inhibition by cytokines. Cytokine inhibition of SERCA2 transcriptional activity was also evident when a 0.6-kb SERCA2 mutant, T-3-unresponsive promoter construct was used. Treatment with T-3 and cytokines showed a significant decrease in transcription when a reporter construct was used that was comprised of direct repeats of SERCA2 thyroid response element I. These data provide evidence for cytokine-mediated inhibitory effects on the SERCA2 promoter that may be mediated by interfering with T-3 action.
引用
收藏
页码:E738 / E743
页数:6
相关论文
共 24 条
[21]  
ROHRER DK, 1991, J BIOL CHEM, V266, P8638
[22]   RABBIT MYOCARDIAL MEMBRANE CA-2+-ADENOSINE TRIPHOSPHATASE-ACTIVITY - STIMULATION INVITRO BY THYROID-HORMONE [J].
RUDINGER, A ;
MYLOTTE, KM ;
DAVIS, PJ ;
DAVIS, FB ;
BLAS, SD .
ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS, 1984, 229 (01) :379-385
[23]   gp130 and the interleukin-6 family of cytokines [J].
Taga, T ;
Kishimoto, T .
ANNUAL REVIEW OF IMMUNOLOGY, 1997, 15 :797-819
[24]   alpha(1)-adrenergic stimulation inhibits 3,5,3'-triiodothyronine-induced expression of the rat heart sarcoplasmic reticulum Ca2+ adenosine triphosphatase gene [J].
Wu, PSC ;
Moriscot, AS ;
Knowlton, KU ;
HilalDandan, R ;
He, HP ;
Dillmann, WH .
ENDOCRINOLOGY, 1997, 138 (01) :114-120