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AJP - Gastrointestinal and Liver Physiology, Vol 264, Issue 2 367-G374, Copyright © 1993 by American Physiological Society
ARTICLES |
S. A. McCormack, M. J. Viar and L. R. Johnson
Department of Physiology and Biophysics, University of Tennessee, College of Medicine, Memphis 38163.
Studies from our laboratory have shown that polyamines are essential for the normal repair of duodenal erosions induced in vivo in a rat stress-ulcer model. In that model, the inhibition of ornithine decarboxylase, a rate-limiting enzyme of polyamine biosynthesis, with alpha-difluoromethylornithine (DFMO) almost entirely prevented healing. Healing could be restored by oral polyamines. In this paper, we have investigated whether the polyamines are required for the early stages of epithelial restitution using an IEC-6 cell culture model of cell migration. Treatment of the cells with DFMO for 4 days reduced cell migration 80%. Migration could be restored to normal by concomitant treatment with putrescine (PUT), spermidine (SPD), or spermine (SPM), but not by their addition during the migration period (6 h) only. If DFMO treatment was not begun until the migration period, it still reduced cell migration 20%, and this deficit could not be restored by concomitant addition of the polyamines. Intracellular polyamine levels at these times, i.e., 6 h or 4 days, were an important factor in these results. Only PUT was undetectable after 6 h of DFMO. SPD and SPM were still at normal levels at 6 h. SPD was undetectable at 4 days, but SPM was still at 40% of normal. These data give added importance to PUT because its absence reduced cell migration after only 6 h, while SPD and SPM were still present in normal amounts. Perhaps exogenous SPD and SPM restored cell migration when present with DFMO for 4 days treatment primarily because they contributed to intracellular PUT through the acetyltransferases.(ABSTRACT TRUNCATED AT 250 WORDS)
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Q. Yuan, R. M. Ray, M. J. Viar, and L. R. Johnson Polyamine regulation of ornithine decarboxylase and its antizyme in intestinal epithelial cells Am J Physiol Gastrointest Liver Physiol, January 1, 2001; 280(1): G130 - G138. [Abstract] [Full Text] [PDF]
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R. M. Ray, B. J. Zimmerman, S. A. McCormack, T. B. Patel, and L. R. Johnson Polyamine depletion arrests cell cycle and induces inhibitors p21Waf1/Cip1, p27Kip1, and p53 in IEC-6 cells Am J Physiol Cell Physiol, March 1, 1999; 276(3): C684 - C691. [Abstract] [Full Text] [PDF]
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S. A. McCormack, R. M. Ray, P. M. Blanner, and L. R. Johnson Polyamine depletion alters the relationship of F-actin, G-actin, and thymosin beta 4 in migrating IEC-6 cells Am J Physiol Cell Physiol, February 1, 1999; 276(2): C459 - C468. [Abstract] [Full Text] [PDF]
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