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Smooth muscle cell response to mechanical injury involves intracellular calcium release and ERK1/ERK2 phosphorylation

Moses, Sara LU ; Dreja, Karl LU ; Lindqvist, Anders LU ; Lövdahl, Cecilia; Hellstrand, Per LU and Hultgårdh, Anna LU (2001) In Experimental Cell Research 269(1). p.88-96
Abstract
We have investigated possible signaling pathways coupled to injury-induced ERK1/2 activation and the subsequent initiation of vascular rat smooth muscle cell migration and proliferation. Aortic smooth muscle cells were cultured to confluency and subjected to in vitro injury under serum-free conditions. In fluo-4-loaded cells, injury induced a rapid wave of intracellular Ca(2+) release that propagated about 200 microm in radius from the injured zone, reached a peak in about 20 s, and subsided to the baseline within 2 min. The wave was abolished by prior treatment with the sarcoplasmic reticulum ATPase inhibitor thapsigargin, but not by omission of extracellular Ca(2+). ERK1/2 activation reached a peak at 10 min after injury and was... (More)
We have investigated possible signaling pathways coupled to injury-induced ERK1/2 activation and the subsequent initiation of vascular rat smooth muscle cell migration and proliferation. Aortic smooth muscle cells were cultured to confluency and subjected to in vitro injury under serum-free conditions. In fluo-4-loaded cells, injury induced a rapid wave of intracellular Ca(2+) release that propagated about 200 microm in radius from the injured zone, reached a peak in about 20 s, and subsided to the baseline within 2 min. The wave was abolished by prior treatment with the sarcoplasmic reticulum ATPase inhibitor thapsigargin, but not by omission of extracellular Ca(2+). ERK1/2 activation reached a peak at 10 min after injury and was inhibited by the MEK1 inhibitor PD98059, as well as by thapsigargin, fluphenazine, genistein, and the Src inhibitor PP2. These inhibitors also reduced [(3)H]thymidine incorporation and migration of cells into the injured area determined at 48 h after injury. These results show that mechanical injury to vascular smooth muscle cells induces a Ca(2+) wave which is dependent on intracellular Ca(2+) release. Furthermore, the injury activates ERK1/2 phosphorylation as well as cell migration and replication. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
smooth muscle cells, Ca2+, ERK1/2, injury, migration, proliferation
in
Experimental Cell Research
volume
269
issue
1
pages
88 - 96
publisher
Academic Press
external identifiers
  • pmid:11525642
  • scopus:0035840152
ISSN
1090-2422
DOI
10.1006/excr.2001.5308
language
English
LU publication?
yes
id
59e22287-25bf-430d-9512-72791d0a26e2 (old id 1120806)
date added to LUP
2008-07-08 09:37:55
date last changed
2018-08-05 03:30:48
@article{59e22287-25bf-430d-9512-72791d0a26e2,
  abstract     = {We have investigated possible signaling pathways coupled to injury-induced ERK1/2 activation and the subsequent initiation of vascular rat smooth muscle cell migration and proliferation. Aortic smooth muscle cells were cultured to confluency and subjected to in vitro injury under serum-free conditions. In fluo-4-loaded cells, injury induced a rapid wave of intracellular Ca(2+) release that propagated about 200 microm in radius from the injured zone, reached a peak in about 20 s, and subsided to the baseline within 2 min. The wave was abolished by prior treatment with the sarcoplasmic reticulum ATPase inhibitor thapsigargin, but not by omission of extracellular Ca(2+). ERK1/2 activation reached a peak at 10 min after injury and was inhibited by the MEK1 inhibitor PD98059, as well as by thapsigargin, fluphenazine, genistein, and the Src inhibitor PP2. These inhibitors also reduced [(3)H]thymidine incorporation and migration of cells into the injured area determined at 48 h after injury. These results show that mechanical injury to vascular smooth muscle cells induces a Ca(2+) wave which is dependent on intracellular Ca(2+) release. Furthermore, the injury activates ERK1/2 phosphorylation as well as cell migration and replication.},
  author       = {Moses, Sara and Dreja, Karl and Lindqvist, Anders and Lövdahl, Cecilia and Hellstrand, Per and Hultgårdh, Anna},
  issn         = {1090-2422},
  keyword      = {smooth muscle cells,Ca2+,ERK1/2,injury,migration,proliferation},
  language     = {eng},
  number       = {1},
  pages        = {88--96},
  publisher    = {Academic Press},
  series       = {Experimental Cell Research},
  title        = {Smooth muscle cell response to mechanical injury involves intracellular calcium release and ERK1/ERK2 phosphorylation},
  url          = {http://dx.doi.org/10.1006/excr.2001.5308},
  volume       = {269},
  year         = {2001},
}