AJP - Renal Ad Instruments
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

Am J Physiol Renal Physiol 278: F1022-F1029, 2000;
0363-6127/00 $5.00
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Web of Science (9)
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Sharma, K.
Right arrow Articles by Hajnóczky, G.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Sharma, K.
Right arrow Articles by Hajnóczky, G.
Vol. 278, Issue 6, F1022-F1029, June 2000

Inhibition of type I and III IP3Rs by TGF-beta is associated with impaired calcium release in mesangial cells

Kumar Sharma1, Tracy A. Mc Gowan1, Lewei Wang1, Muniswamy Madesh2, Vince Kaspar1, Gabor Szalai2, Andrew P. Thomas2, and György Hajnóczky2

1 Department of Medicine and 2 Department of Anatomy, Cell Biology, and Pathology, Thomas Jefferson University, Philadelphia, Pennsylvania 19107

Inositol 1,4,5-trisphosphate receptors (IP3Rs) mediate cytosolic free calcium concentration ([Ca2+]c) signals in response to a variety of agonists that stimulate mesangial cell contraction and proliferation. In the present study, we demonstrate that mesangial cells express both type I and III IP3Rs and that these receptors occupy different cellular locations. Chronic treatment with transforming growth factor-beta 1 (TGF-beta 1; 10 ng/ml, 24 h) leads to downregulation of both type I and III IP3Rs as measured by immunoblot and confocal analysis. TGF-beta 1 treatment does not affect IP3 levels, and downregulation of type I IP3R is not due to enhanced degradation of the protein, as the half-life of type I IP3R is unchanged in the presence or absence of TGF-beta 1. Functional effects of TGF-beta 1-induced downregulation of the IP3Rs were evaluated by measuring [Ca2+]c changes in response to epidermal growth factor (EGF) in intact cells and sensitivity of [Ca2+]c release to IP3 in permeabilized cells. TGF-beta 1 pretreatment led to a significant decrease of [Ca2+]c release induced by EGF in intact cells and by submaximal IP3 (400 nm) in permeabilized cells. Total IP3-sensitive [Ca2+]c stores were not changed, as assessed by stimulation with maximal doses of IP3 (10.5 µm) and thapsigargin-mediated calcium release in permeabilized cells. We conclude that prolonged exposure to TGF-beta 1 leads to downregulation of both type I and III IP3Rs in mesangial cells and this is associated with impaired sensitivity to IP3.

transforming growth factor-beta 1; inositol 1,4,5-trisphosphate receptors; calcium mobilization; mesangial cells


This article has been cited by other articles:


Home page
 Am. J. Physiol. Renal Physiol.Home page
S. P. R. Rao, R. Wassell, M. A. Shaw, and K. Sharma
Profiling of human mesangial cell subproteomes reveals a role for calmodulin in glucose uptake
Am J Physiol Renal Physiol, April 1, 2007; 292(4): F1182 - F1189.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Renal Physiol.Home page
K. Sharma, L. Deelman, M. Madesh, B. Kurz, E. Ciccone, S. Siva, T. Hu, Y. Zhu, L. Wang, R. Henning, et al.
Involvement of transforming growth factor-{beta} in regulation of calcium transients in diabetic vascular smooth muscle cells
Am J Physiol Renal Physiol, December 1, 2003; 285(6): F1258 - F1270.
[Abstract] [Full Text]

Home page
 Am. J. Physiol. Renal Physiol.Home page
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
Visit Other APS Journals Online