|
|
||||||||
Department of Medicine, University of California San Diego, La Jolla, California 92093-0618
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 (T3)-stimulated sarcoplasmic reticulum Ca2+ ATPase (SERCA2) gene expression on cultured neonatal rat cardiac myocytes. A reduction of T3 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. T3 treatment stimulated transcriptional activity twofold, whereas co-treatment with T3 and either of the cytokines caused an inhibition of T3-induced SERCA2 transcriptional activity. A T3-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, T3-unresponsive promoter construct was used. Treatment with T3 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 T3 action.
cardiac hypertrophy; heart failure; contraction; relaxation; cytokines
This article has been cited by other articles:
![]() |
N. A. Abdel-Malak, C. B. Srikant, A. S. Kristof, S. A. Magder, J. A. Di Battista, and S. N. A. Hussain Angiopoietin-1 promotes endothelial cell proliferation and migration through AP-1-dependent autocrine production of interleukin-8 Blood, April 15, 2008; 111(8): 4145 - 4154. [Abstract] [Full Text] [PDF] |
||||
![]() |
K.-D. Wu, D. Bungard, and J. Lytton Regulation of SERCA Ca2+ pump expression by cytoplasmic [Ca2+] in vascular smooth muscle cells Am J Physiol Cell Physiol, April 1, 2001; 280(4): C843 - C851. [Abstract] [Full Text] [PDF] |
||||
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Visit Other APS Journals Online |