|
|
||||||||
1 Department of Medicine, McMaster University, Hamilton, Ontario L8N 1Y2; and 2 University of Toronto, Toronto, Ontario, Canada M55 1A8
Mesangial cells (MC), grown on
extracellular matrix (ECM) protein-coated plates and stretched,
proliferate and produce ECM, recapitulating in vivo responses to
increased glomerular capillary pressure (Pgc). Transduction of strain
involves mitogen-activated protein kinases (MAPK), and we have shown
that p38 MAPK is activated by strain in MC. Because in vivo studies
show that nitric oxide (NO) in the remnant kidney limits glomerular
injury without reducing Pgc, we studied whether NO attenuated
stretch-induced p38 activation in MC. Increasing p38 activation
occurred with increasing stretch, maximally at 10 min at
27-kPa
vacuum. Cyclic strain increased nuclear translocation of phosphorylated
p38 by immunofluorescent microscopy and nuclear protein binding to
nuclear factor-
B (NF-
B) consensus sequences by mobility shift
assay. Both events were largely abrogated by the p38 inhibitor
SB-203580. The NO donors 3-morpholinosydnonimine,
S-nitroso-N-acetylpenicillamine, and 8-bromoguanosine 3',5'-cyclic monophosphate, a stable cGMP analog, prevented p38 activation and nulcear translocation. Thus strain induces
p38 activity and translocation to the nucleus and p38-dependent increases in nuclear protein binding to NF-
B. This pathway is attenuated by the NO donors or a cGMP analog.
nuclear factor-
B; kidney glomerulus; physical forces; mitogen-activated protein kinases; signaling
This article has been cited by other articles:
![]() |
L. C. Martineau, L. I. McVeigh, B. J. Jasmin, and C. R. J. Kennedy p38 MAP kinase mediates mechanically induced COX-2 and PG EP4 receptor expression in podocytes: implications for the actin cytoskeleton Am J Physiol Renal Physiol, April 1, 2004; 286(4): F693 - F701. [Abstract] [Full Text] [PDF] |
||||
![]() |
L. R. James, D. Tang, A. Ingram, H. Ly, K. Thai, L. Cai, and J. W. Scholey Flux Through the Hexosamine Pathway Is a Determinant of Nuclear Factor {kappa}B- Dependent Promoter Activation Diabetes, April 1, 2002; 51(4): 1146 - 1156. [Abstract] [Full Text] [PDF] |
||||
![]() |
J. Krepinsky, A. J. Ingram, L. James, H. Ly, K. Thai, D. C. Cattran, J. A. Miller, and J. W. Scholey 17beta -Estradiol Modulates Mechanical Strain-induced MAPK Activation in Mesangial Cells J. Biol. Chem., March 8, 2002; 277(11): 9387 - 9394. [Abstract] [Full Text] [PDF] |
||||
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Visit Other APS Journals Online |