In:
American Journal of Physiology-Heart and Circulatory Physiology, American Physiological Society, Vol. 279, No. 4 ( 2000-10-01), p. H1635-H1644
Abstract:
We compared the role of the Raf-1/mitogen-activated protein kinase/extracellular signal-regulated protein kinase (MEK)/extracellular signal-regulated protein kinase (ERK)/p90 RSK cascade in gp130-mediated cardiac hypertrophy with the contribution of the Janus kinase (JAK)/signal transduction and activation of transcription (STAT) and phosphatidylinositide 3-kinase (PI3-K) pathways. Primary cultured neonatal rat cardiomyocytes were stimulated with leukemia inhibitory factor (LIF). LIF sequentially activated Raf-1, MEK1/2, ERK1/2, and p90 RSK . We used PD-98059 (a specific MEK inhibitor), AG-490 (a JAK2 inhibitor), and wortmannin (a PI3-K inhibitor) to confirm that this cascade was independent of the JAK/STAT and PI3-K/p70 S6 kinase (S6K) pathways. PD-98059, AG-490, and wortmannin suppressed the LIF-induced increase in [ 3 H]phenylalanine uptake by 54.7, 21.5, and 25.6%, respectively, and inhibited the increase in cell area by 61.2, 42.8, and 39.2%, respectively. Reorganization of myofilaments was predominantly suppressed by AG-490. LIF-induced expression of c- fos, brain natriuretic peptide, and skeletal α-actin mRNA was markedly suppressed by PD-98059 and moderately suppressed by wortmannin and AG-490. Atrial natriuretic peptide was significantly suppressed by AG-490. These findings indicate that this pathway is critically involved in protein synthesis, induction of c- fos, brain natriuretic peptide, and skeletal α-actin expression and is partially involved in myofilament reorganization and atrial natriuretic peptide induction in gp130-mediated cardiac hypertrophy.
Type of Medium:
Online Resource
ISSN:
0363-6135
,
1522-1539
DOI:
10.1152/ajpheart.2000.279.4.H1635
Language:
English
Publisher:
American Physiological Society
Publication Date:
2000
detail.hit.zdb_id:
1477308-9
SSG:
12
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