1 330

Cited 5 times in

Adherens junction-dependent PI3K/Akt activation induces resistance to genotoxin-induced cell death in differentiated intestinal epithelial cells.

Authors
 Boah Chae  ;  Kyoung Min Yang  ;  Tae Il Kim  ;  Won Ho Kim 
Citation
 BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, Vol.378(4) : 738-743, 2009 
Journal Title
 BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS 
ISSN
 0006-291X 
Issue Date
2009
MeSH
Adherens Junctions/enzymology* ; Apoptosis* ; Caco-2 Cells ; Cadherins/metabolism ; Calcium/metabolism ; Cell Adhesion/drug effects ; Cell Differentiation ; Chromones/pharmacology ; Cyclin-Dependent Kinase Inhibitor p21/biosynthesis ; Drug Resistance* ; Humans ; Intestinal Mucosa/cytology ; Intestinal Mucosa/drug effects* ; Intestinal Mucosa/enzymology ; Methyl Methanesulfonate/pharmacology ; Morpholines/pharmacology ; Mutagens/pharmacology* ; NF-kappa B/metabolism ; Phosphatidylinositol 3-Kinases/antagonists & inhibitors ; Phosphatidylinositol 3-Kinases/metabolism* ; Protein Kinase Inhibitors/pharmacology ; Proto-Oncogene Proteins c-akt/agonists ; Proto-Oncogene Proteins c-akt/metabolism* ; beta Catenin/metabolism
Keywords
Differentiation ; Cell death ; MMS ; E-cadherin ; Akt
Abstract
The crypt-villi axis of intestinal mucosa maintains homeostasis by renewal of epithelia, and also exhibits different properties from undifferentiated to terminally differentiated cells. We investigated differential susceptibility to genotoxin-induced cell death, based on the degree of differentiation of epithelial cells, and its mechanism. Differentiation was induced by post-confluence culture in Caco-2 cells. Methyl methanesulfonate (MMS), a direct-acting DNA alkylating agent, was used for genotoxin-induced cell death. Compared to subconfluent Caco-2 cells, 7 days post-confluent cells showed resistance to MMS-induced cell death. With increasing expression of adherens junction components of E-cadherin and beta-catenin, E-cadherin and p-Akt expression increased in 7 days post-confluent Caco-2 cells, and in human intestinal tissue, expression of E-cadherin and p-Akt also increased in the upper portion of villi, compared to the crypt. Inhibition of cell-cell adhesion using EGTA decreased Akt phosphorylation, which was reversed by calcium restoration. Akt phosphorylation by calcium-mediated cell-cell adhesion was more prominent in differentiated cells. In addition, treatment of a PI3K inhibitor, LY294002, inhibited Akt phosphorylation by calcium-mediated cell-cell adhesion. Finally, the differential sensitivity to MMS-induced cell death between subconfluent and 7 days post-confluent Caco-2 cells was eliminated by inhibiting cell-cell adhesion or PI3K. Our data demonstrated that cell adhesion-mediated PI3K/Akt activation could be one of the important mechanisms of resistance to genotoxin-induced cell death in differentiated epithelial cells.
Full Text
http://www.sciencedirect.com/science/article/pii/S0006291X08023073
DOI
10.1016/j.bbrc.2008.11.120
Appears in Collections:
1. College of Medicine (의과대학) > Medical Research Center (임상의학연구센터) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
Yonsei Authors
Kim, Won Ho(김원호) ORCID logo https://orcid.org/0000-0002-5682-9972
Kim, Tae Il(김태일) ORCID logo https://orcid.org/0000-0003-4807-890X
Yang, Kyoung Min(양경민)
Chae, Bo Ah(채보아)
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/103351
사서에게 알리기
  feedback

qrcode

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.

Browse

Links