Role of non-muscle myosin ii in polyamine-dependent intestinal
epithelial cell migration.
Wang, Jian-Ying, Shirley A. McCormack, and Leonard R. Johnson.
Department of Surgery, University of Maryland Medical School and
Baltimore VA Medical Center, Baltimore, MD 21201. Department of
physiology and Biophysics, University of Tennessee College of
Medicine, Memphis, TN 38163
APStracts 2:0151G, 1995.
The current study determines whether non-muscle myosin II is involved
in the process requiring polyamines for the stimulation of cell
migration in an in vitro model which mimics the early stages of
epithelial restitution. Treatment with -difluoromethylornithine
(DFMO), a specific inhibitor of ornithine decarboxylase (ODC), for 4
days totally inhibited ODC activity and depleted intracellular
polyamines in the IEC-6 cells. Non-muscle myosin II concentrations in
DFMO-treated cells were decreased by 75% and stress fibers were
sparse or lacking. The most striking feature of DFMO-treated cells
was the appearance of many small punctate foci of myosin II in the
cell interior. Cell migration of DFMO-treated cells was reduced by
80%. In the presence of DFMO, exogenous putrescine not only returned
non-muscle myosin II levels and distribution toward normal but also
restored cell migration to control levels. The administration of
wortmanin, an inhibitor of myosin light chain kinase, significantly
inhibited cell migration over denuded area in control cells and in
those treated with DFMO plus polyamines. These results indicate that
1) polyamine depletion by DFMO is associated with both decreased
concentration and reorganization of non-muscle myosin II in IEC-6
cells, and 2) exogenous spermidine reverses the inhibitory effects of
DFMO.
Received 25 April 1995; accepted in final form 21 July 1995.
APS Manuscript Number G171-5.
Article publication pending Am. J. Physiol. (Gastrointest. Liver
Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 10 August 1995.