TY - JOUR
T1 - Effects of pancreatic spasmolytic polypeptide (PSP) on epithelial cell function
AU - Otto, William R.
AU - Rao, Jagdish
AU - Cox, Helen M.
AU - Kotzian, Ewald
AU - Lee, Chung Y.
AU - Goodlad, Robert A.
AU - Lane, Andrew
AU - Gorman, Michael
AU - Freemont, Paul A.
AU - Hansen, Hans F.
AU - Pappin, Darryl
AU - Wright, Nicholas A.
PY - 1996
Y1 - 1996
N2 - Trefoil peptides are expressed near endodermal ulcerations and may modulate epithelial repair. The trefoil pancreatic spasmolytic polypeptide (PSP) was tested for growth activity in vitro on epithelial cells and in vivo following intragastric or intravenous infusion in parenterally fed intact rats. Ion transport was assessed as changes in short-circuit current in rat intestine and adenocarcinoma cells in Ussing chambers. PSP stimulated growth of MCF-7 and Colo-357 cells, but only in the presence of extracellular glutathione (GSH). The effect was attenuated by GSH depletion with buthionine sulphoximine, even in GSH-containing media. When GSH-reduced PSP was carboxymethylated with iodoacetic acid, it still depended on extracellular GSH for its growth effect. Intestinal epithelial proliferation in rats was not affected by either intravenous or intraluminal infusion. PSP had no effect on basal or stimulated ion flux in rat jejunum or epithelial monolayers. The peptide did not compete with 125I-labeled epidermal growth factor for its receptor. [14C]Iodoacetamide treatment of PSP, followed by prolonged tryptic digestion yielded predominantly a 14C-labeled tetrapeptide fragment containing Cys104, with a lesser quantity of a 14C-labeled 15-amino-acid peptide containing Cys95 (molar ratio 15:l). GSH may predominantly reduce the Cys6-Cys104 terminal disulphide bond in PSP. We conclude that some epithelia may exhibit a growth response to PSP if extracellular GSH is present. Reduction of PSP by GSH is not necessary for this response, suggesting that the trefoil receptor or its signal transduction is GSH sensitive. PSP could assist wound healing by interactions with epithelial cells exposed concurrently to a local high GSH concentration.
AB - Trefoil peptides are expressed near endodermal ulcerations and may modulate epithelial repair. The trefoil pancreatic spasmolytic polypeptide (PSP) was tested for growth activity in vitro on epithelial cells and in vivo following intragastric or intravenous infusion in parenterally fed intact rats. Ion transport was assessed as changes in short-circuit current in rat intestine and adenocarcinoma cells in Ussing chambers. PSP stimulated growth of MCF-7 and Colo-357 cells, but only in the presence of extracellular glutathione (GSH). The effect was attenuated by GSH depletion with buthionine sulphoximine, even in GSH-containing media. When GSH-reduced PSP was carboxymethylated with iodoacetic acid, it still depended on extracellular GSH for its growth effect. Intestinal epithelial proliferation in rats was not affected by either intravenous or intraluminal infusion. PSP had no effect on basal or stimulated ion flux in rat jejunum or epithelial monolayers. The peptide did not compete with 125I-labeled epidermal growth factor for its receptor. [14C]Iodoacetamide treatment of PSP, followed by prolonged tryptic digestion yielded predominantly a 14C-labeled tetrapeptide fragment containing Cys104, with a lesser quantity of a 14C-labeled 15-amino-acid peptide containing Cys95 (molar ratio 15:l). GSH may predominantly reduce the Cys6-Cys104 terminal disulphide bond in PSP. We conclude that some epithelia may exhibit a growth response to PSP if extracellular GSH is present. Reduction of PSP by GSH is not necessary for this response, suggesting that the trefoil receptor or its signal transduction is GSH sensitive. PSP could assist wound healing by interactions with epithelial cells exposed concurrently to a local high GSH concentration.
KW - glutathione
KW - pancreatic spasmolytic polypeptide
KW - proliferation
KW - short-circuit current
KW - total parenteral nutrition
KW - trefoil peptide
UR - http://www.scopus.com/inward/record.url?scp=9044227256&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=9044227256&partnerID=8YFLogxK
U2 - 10.1111/j.1432-1033.1996.00064.x
DO - 10.1111/j.1432-1033.1996.00064.x
M3 - Article
C2 - 8631368
AN - SCOPUS:9044227256
SN - 0014-2956
VL - 235
SP - 64
EP - 72
JO - European Journal of Biochemistry
JF - European Journal of Biochemistry
IS - 1-2
ER -