Bile acid modulates transepithelial permeability via the generation of reactive oxygen species in the Caco-2 cell line

被引:89
作者
Araki, Y
Katoh, T
Ogawa, A
Bamba, S
Andoh, A
Koyama, S
Fujiyama, Y
Bamba, T
机构
[1] Biwako Youikuin Hosp, Dept Internal Med, Shiga 5202144, Japan
[2] Shiga Univ Med Sci, Div Gastroenterol & Hematol, Shiga 5202192, Japan
关键词
bile acids; transepithelial permeability; intracellular signaling pathways; reactive oxygen species;
D O I
10.1016/j.freeradbiomed.2005.04.026
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The barrier functions in epithelial and endothelial cells seem to be very important for maintaining normal biological homeostasis. However, it is unclear whether or how bile acids affect the epithelial barrier. We examined the bile acid-induced disruption of the epithelial barrier. We measured the transepithelial electrical resistance (TEER) of Caco-2 cells as a marker of disruption of the epithelial barrier. Reactive oxygen species (ROS) generation was also measured. Cholic, acid (CA) decreased the TEER and increased intracellular ROS generation. PLA2 (phospholipase A2), COX (cyclooxygenase), PKC (protein kinase), ERK1/2 (extracellular signal-regulated kinase 1/2), PI3K (phosphatidylinositol 3-kinase), p38 MAPK (p38 mitogen-activated protein kinase), MLCK (myosin light-chain kinase), NADH dehydrogenase, and XO (xanthine oxidase) inhibitors or ROS scavengers prevented the CA-induced TEER decrease. PLA2, COX, PKC, NADH dehydrogenase, and XO inhibitors prevented the CA-induced ROS generation but not ERK1/2, PI3K, p38 MAPK, and MLCK inhibitors. If the cells were treated with ROS generators such as superoxide dismutase, the TEER decreased. ERK1/2, PI3K, p38 MAPK, and MLCK inhibitors prevent these ROS generators from inducing the TEER decrease. These results suggest that ROS play an important role. In addition, PLA2, COX, PKC, NADH dehydrogenase, and XO are located upstream of the ROS generation, but ERK1/2, PI3K, p38 MAPK, and MLCK are downstream during the signaling of CA-induced TEER alterations. (c) 2005 Elsevier Inc. All rights reserved.
引用
收藏
页码:769 / 780
页数:12
相关论文
共 41 条
[1]   Identification of the hydroxyl radical and other reactive oxygen species in human neutrophil granulocytes exposed to a fragment of the amyloid beta peptide [J].
Andersen, JM ;
Myhre, O ;
Aarnes, H ;
Vestad, TA ;
Fonnum, F .
FREE RADICAL RESEARCH, 2003, 37 (03) :269-279
[2]   Hydrophilic and hydrophobic bile acids exhibit different cytotoxicities through cytolysis, interleukin-8 synthesis and apoptosis in the intestinal epithelial cell lines. IEC-6 and Caco-2 cells [J].
Araki, Y ;
Fujiyama, Y ;
Andoh, A ;
Nakamura, F ;
Shimada, M ;
Takaya, H ;
Bamba, T .
SCANDINAVIAN JOURNAL OF GASTROENTEROLOGY, 2001, 36 (05) :533-539
[3]  
Balda MS, 1998, J CELL SCI, V111, P541
[4]   Key role of PKC and Ca2+ in EGF protection of microtubules and intestinal barrier against oxidants [J].
Banan, A ;
Fields, JZ ;
Zhang, Y ;
Keshavarzian, A .
AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY, 2001, 280 (05) :G828-G843
[5]   iNOS upregulation mediates oxidant-induced disruption of F-actin and barrier of intestinal monolayers [J].
Banan, A ;
Fields, JZ ;
Zhang, Y ;
Keshavarzian, A .
AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY, 2001, 280 (06) :G1234-G1246
[6]   EFFECT OF NONSTEROIDAL ANTIINFLAMMATORY DRUGS AND PROSTAGLANDINS ON THE PERMEABILITY OF THE HUMAN SMALL-INTESTINE [J].
BJARNASON, I ;
WILLIAMS, P ;
SMETHURST, P ;
PETERS, TJ ;
LEVI, AJ .
GUT, 1986, 27 (11) :1292-1297
[7]   ROLE OF REACTIVE OXYGEN IN BILE-SALT STIMULATION OF COLONIC EPITHELIAL PROLIFERATION [J].
CRAVEN, PA ;
PFANSTIEL, J ;
DERUBERTIS, FR .
JOURNAL OF CLINICAL INVESTIGATION, 1986, 77 (03) :850-859
[8]   ROLE OF ACTIVATION OF PROTEIN-KINASE-C IN THE STIMULATION OF COLONIC EPITHELIAL PROLIFERATION AND REACTIVE OXYGEN FORMATION BY BILE-ACIDS [J].
CRAVEN, PA ;
PFANSTIEL, J ;
DERUBERTIS, FR .
JOURNAL OF CLINICAL INVESTIGATION, 1987, 79 (02) :532-541
[9]   Contribution of macrophage migration inhibitory factor to extracellular signal-regulated kinase activation by oxidative stress in cardiomyocytes [J].
Fukuzawa, J ;
Nishihira, J ;
Hasebe, N ;
Haneda, T ;
Osaki, J ;
Saito, T ;
Nomura, T ;
Fujino, T ;
Wakamiya, N ;
Kikuchi, K .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2002, 277 (28) :24889-24895
[10]   OCCLUDIN - A NOVEL INTEGRAL MEMBRANE-PROTEIN LOCALIZING AT TIGHT JUNCTIONS [J].
FURUSE, M ;
HIRASE, T ;
ITOH, M ;
NAGAFUCHI, A ;
YONEMURA, S ;
TSUKITA, S ;
TSUKITA, S .
JOURNAL OF CELL BIOLOGY, 1993, 123 (06) :1777-1788