|
|
|
|||||||
|
|||||||||
(Received for publication, March 29, 1996, and in revised form, May 1, 1996)
From the Departments of Heparin suppresses mitogenic responses in
renal mesangial cells, and when quiescent mesangial cells are
stimulated with serum, heparin blocks the induction of
c-fos seen at 15 min. Because heparin is taken up by cells
over a much longer time course, we addressed mechanisms whereby
extracellular heparin might suppress c-fos induction at
such early times. Quiescent cells were treated with serum,
12-O-tetradecanoylphorbol-13-acetate, or low concentrations
of Ca2+ ionophores that produced increases in intracellular
Ca2+ concentration ([Ca2+]i) in the
physiological range. Each treatment caused an increase in
c-fos mRNA, but they did so by different mechanisms.
Serum activated mitogen-activated protein kinase (MAPK) and increased
[Ca2+]i without affecting protein kinase C. Activation of protein kinase C with phorbol ester activated MAPK
without much effect on [Ca2+]i. Ionophores
increased [Ca2+]i without affecting basal levels
of protein kinase C or MAPK. Heparin (1 µg/ml) suppressed the
induction of c-fos initiated by all three treatments. It
did not affect the activity of protein kinase C, but inhibited
activation of MAPK by either serum or phorbol ester, suggesting a
common site of action at or below the probable convergence of the
induced signals at Ras/Raf-1 activation. Heparin also inhibited the
serum-stimulated entry of extracellular Ca2+ to the same
extent as verapamil, consistent with the ability of verapamil to block
L-type Ca2+ channels and the known presence of these
channels in mesangial cells. However, this effect does not appear to be
related to heparin's ability to inhibit induction of
c-fos. First, verapamil had no effect on induction of
c-fos by serum. Second, heparin had no effect on changes in
[Ca2+]i achieved by ionophores. We conclude that
heparin suppresses induction of c-fos in mesangial cells by
blocking at least two different points in signal transduction cascades,
one upstream of MAPK and the other independent of MAPK, but dependent
on intracellular Ca2+.
Volume 271, Number 29,
Issue of July 19, 1996
pp. 17100-17106
©1996 by The American Society for Biochemistry and Molecular Biology, Inc.
,
,§
and¶
Clinical Biochemistry and
§ Medicine, University of Toronto and the
¶ Department of Biochemistry, Hospital for Sick Children,
Toronto, Canada
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati What's this?
This article has been cited by other articles:
|
|
 |
|
  K. UEDA, S. INOUE, Y. ZHANG, T. KUTSUNA, S. INOUE, K. NOTO, N. ARAI, and M. NOGUCHI Heparin Induces Apoptosis through Suppression of AKt in Oral Squamous Cell Carcinoma Cells Anticancer Res, April 1, 2009; 29(4): 1079 - 1088. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Fasciano, R. C. Patel, I. Handy, and C. V. Patel Regulation of Vascular Smooth Muscle Proliferation by Heparin: INHIBITION OF CYCLIN-DEPENDENT KINASE 2 ACTIVITY BY p27kip1 J. Biol. Chem., April 22, 2005; 280(16): 15682 - 15689. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Zayzafoon, K. Fulzele, and J. M. McDonald Calmodulin and Calmodulin-dependent Kinase II{alpha} Regulate Osteoblast Differentiation by Controlling c-fos Expression J. Biol. Chem., February 25, 2005; 280(8): 7049 - 7059. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W. Xiao, Y. Liu, and D. M. Templeton Ca2+/calmodulin-dependent protein kinase II inhibition by heparin in mesangial cells Am J Physiol Renal Physiol, January 1, 2005; 288(1): F142 - F149. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. R. Newman, C.-M. Li, R. Simmons, J. Khosla, and P. L. Sannes Heparin affects signaling pathways stimulated by fibroblast growth factor-1 and -2 in type II cells Am J Physiol Lung Cell Mol Physiol, July 1, 2004; 287(1): L191 - L200. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Miralem and H. K. Avraham Extracellular Matrix Enhances Heregulin-Dependent BRCA1 Phosphorylation and Suppresses BRCA1 Expression through Its C Terminus Mol. Cell. Biol., January 15, 2003; 23(2): 579 - 593. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Mishra-Gorur, H. A. Singer, and J. J. Castellot Jr Heparin Inhibits Phosphorylation and Autonomous Activity of Ca2+/Calmodulin-Dependent Protein Kinase II in Vascular Smooth Muscle Cells Am. J. Pathol., November 1, 2002; 161(5): 1893 - 1901. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Zeng, Y. Liu, and D. M. Templeton Ca2+/calmodulin-dependent and cAMP-dependent kinases in induction of c-fos in human mesangial cells Am J Physiol Renal Physiol, November 1, 2002; 283(5): F888 - F894. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. M. Smorenburg and C. J. F. Van Noorden The Complex Effects of Heparins on Cancer Progression and Metastasis in Experimental Studies Pharmacol. Rev., March 1, 2001; 53(1): 93 - 106. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. M Templeton, Y. Zhao, and M. Y. Fan Heterogeneity in the response of vascular smooth muscle to heparin: altered signaling in heparin-resistant cells Cardiovasc Res, January 14, 2000; 45(2): 503 - 512. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Miralem and D. M. Templeton Inactivation of kinase cascades in mesangial cells grown on collagen type I Am J Physiol Renal Physiol, October 1, 1998; 275(4): F585 - F594. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Z. Wang and D. M. Templeton Induction of c-fos Proto-oncogene in Mesangial Cells by Cadmium J. Biol. Chem., January 2, 1998; 273(1): 73 - 79. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. A. McGowan, M. Madesh, Y. Zhu, L. Wang, M. Russo, L. Deelman, R. Henning, S. Joseph, G. Hajnoczky, and K. Sharma TGF-beta -induced Ca2+ influx involves the type III IP3 receptor and regulates actin cytoskeleton Am J Physiol Renal Physiol, May 1, 2002; 282(5): F910 - F920. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| All ASBMB Journals | Molecular and Cellular Proteomics |
| Journal of Lipid Research | ASBMB Today |