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Theodore Cooper Surgical Research Institute, Department of Surgery, Saint Louis University Medical Center, St. Louis, Missouri 63104
Prostaglandins have been shown to protect the
gastrointestinal (GI) epithelium from injury induced by various luminal
insults independent of their known acid-inhibitory effects, a process termed "cytoprotection." The mechanism of this protective action remains unknown. The present investigation determined the role of
microtubules (a major cytoskeletal component) in GI injury induced by
ethanol (EtOH) and its prevention by 16,16-dimethylprostaglandin E2
(dmPGE2) using cells from a
human colonic cell line known as Caco-2 cells. These cells were
preincubated in Eagle's minimum essential medium with and without
dmPGE2 (2.6 µM) for 15 min and subsequently incubated in media containing 1, 2.5, 5, 7.5, and 10%
EtOH. The effects on cell viability and tubulin (the major protein
backbone of microtubules) were then determined. EtOH concentrations 
2.5% extensively disrupted the microtubules as demonstrated by fragmentation, kinking, and perturbation of the microtubule organizer center. EtOH treatment also led to a significant decrease in the S2 (polymerized) fraction and an
increase in the S1 (monomeric) pool of
tubulin. Concomitant with these effects were marked decreases in
cellular viability. DmPGE2
pretreatment abolished the disruption of microtubules, significantly
increased the S2 fraction of tubulin, and increased cellular viability in cultures exposed to EtOH. Furthermore, pretreatment with colchicine, an inhibitor of microtubule assembly, prevented the cytoprotective action of
dmPGE2. Taxol, a microtubule
stabilizing agent, mimicked the effects of
dmPGE2 by also enhancing
microtubule integrity and increasing cellular viability in cells
exposed to EtOH. Our data indicate that organization and stabilization
of microtubules may play an essential role in the mechanism of
prostaglandin-induced protection.
16,16-dimethylprostaglandin E2; cytoskeleton; Taxol; colchicine; Caco-2 cells; tubulin; quantitative Western immunoblot
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