当前位置： SCI文献检索 > GASTROENTEROLOGY期刊下所有文献 > Hydrocortisone modulates cholera toxin endocytosis by regulating immature enterocyte plasma membrane phospholipids.

Hydrocortisone modulates cholera toxin endocytosis by regulating immature enterocyte plasma membrane phospholipids.

Abstract：

BACKGROUND & AIMS:Diarrheal disease is a major cause of morbidity and mortality in infants and children worldwide. Evidence has indicated immature human enterocytes and their interaction with bacteria and enterotoxins may account for the noted increased susceptibility of neonates to diarrhea. Our aim was to characterize the developmental difference in cholera toxin (CT)-GM1-mediated endocytosis. METHODS:We used H4 cells (a fetal human small intestinal epithelial cell line), T84 cells, primary cultured mature human small intestinal epithelial cells, and human fetal small intestine xenografts. In addition, hydrocortisone was used as a potent intestinal trophic factor to induce maturation of the human enterocytes. RESULTS:Here we show an increase in CT-caveolae and a decrease in CT-clathrin colocalization in H4/hydrocortisone compared with H4 cells by electron microscopy. In T84 and freshly isolated human small intestinal epithelial cells, a significant amount of GM1 was partitioned into the lipid rafts. In contrast, there was little CT-GM1/lipid raft association in H4 cells. However, hydrocortisone significantly increased GM1/lipid raft association in H4 cells. Furthermore, we noted an increase in the level of phosphatidylcholine, sphingomyelin, and the ratio of phosphatidylcholine/phosphatidylinositol in mature compared with immature enterocytes and that hydrocortisone can accelerate this maturational process. Disruption of phosphatidylinositol transfer protein alpha using small interference RNA showed an increase in GM1/lipid raft association in H4 cells and resulted in a decreased CT response. CONCLUSIONS:Our studies suggest that the developmental change in CT endocytosis is partially caused by an increased GM1-lipid raft association through a maturational change of phospholipid composition on the cell surface of immature enterocytes.

journal_name

Gastroenterology

journal_title

Gastroenterology

authors

Lu L,Bao Y,Khan A,Goldstein AM,Newburg DS,Quaroni A,Brown D,Walker WA

doi

10.1053/j.gastro.2008.03.038

subject

Has Abstract

pub_date

2008-07-01 00:00:00

pages

185-193.e1

issue

eissn

0016-5085

issn

1528-0012

pii

S0016-5085(08)00474-5

journal_volume

135

pub_type

杂志文章

在线工具

Hydrocortisone modulates cholera toxin endocytosis by regulating immature enterocyte plasma membrane phospholipids.