Calcium-mediated oxidative stress: a common mechanism in tight junction disruption by different types of cellular stress

Abstract

The role of reactive oxygen species (ROS) in osmotic stress, dextran sulfate sodium (DSS) and cyclic stretch-induced tight junction disruption was investigated in Caco-2 cell monolayers in vitro, and restraint stress-induced barrier dysfunction in mouse colon in vivo. Live cell imaging showed that osmotic stress, cyclic stretch and DSS triggered rapid production of ROS in Caco-2 cell monolayers, which was blocked by depletion of intracellular Ca2+ by BAPTA. Knockdown of CaV1.3 or TRPV6 channels blocked osmotic stress and DSS-induced ROS production and attenuated tight junction disruption and barrier dysfunction. N-acetyl L-cysteine (NAC) and L-nitroarginine methyl ester (L-NAME) blocked stress-induced tight junction disruption and barrier dysfunction. NAC and L-NAME also blocked stress-induced activation of JNK and c-Src. ROS was co-localized with the mitochondrial marker in stressed cells. Cyclosporin A blocked osmotic stress and DSS-induced ROS production, barrier dysfunction, tight junction disruption and JNK activation. Mitochondria-targeted Mito-TEMPO blocked osmotic stress and DSS-induced barrier dysfunction and tight junction disruption. Chronic restraint stress in mice resulted in the elevation of intracellular Ca2+, activation of JNK and c-Src, and disruption of tight junction in the colonic epithelium. Furthermore, corticosterone administration induced JNK and c-Src activation, tight junction disruption and protein thiol oxidation in colonic mucosa. This study demonstrates that oxidative stress is a common signal in the mechanism of tight junction disruption in the intestinal epithelium by different types of cellular stress in vitro and bio behavioral stress in vivo.

Icariin and its phosphorylated derivatives alleviate intestinal epithelial barrier disruption caused by enterotoxigenic Escherichia coli through modulate p38 MAPK in vivo and in vitro

“…40,41 In the present study, our data showed that ETEC K88 challenge significantly increased the gene abundance and concentrations of IL-1β, IL-6, IL-8, and TNF-α in jejunum of piglets and IPEC-J2 cells. 45,46 Our data clearly showed that ETEC K88 challenge expression of p38 in IPEC-J2 cells. Oxidative stress is a very important mechanism in many potential mechanisms by which toxic substances affect mammalian cells.…”

“…44 Besides, evidences suggested that oxidative stress is closely related to intestinal barrier dysfunction, mainly due to the ability of oxidative stress to disrupt TJ proteins. 45,46 Our data clearly showed that ETEC K88 challenge expression of p38 in IPEC-J2 cells. Data are represented as means ± SEM, n = 6, *P < .05 vs CON group; # P < .05 vs ETEC K88 group.…”

Effects of dietary lysozyme levels on growth performance, intestinal morphology, immunity response and microbiota community of growing pigs

“…18,39,40 Under oxidative stress conditions, reactive oxygen species synthesis can trigger greater prevalence of pathogenic microorganisms as a result of compromised immune cell functions, which could subsequently lead to defects in gastrointestinal barrier function. 41,42 The present study showed that there were no differences in activity of antioxidant enzyme and protein expression of occludin, claudin1 and claudin3 among pigs consuming colistin sulfate or lysozyme diets. These observations indicate lysozyme did not affect the antioxidant capacity and tight junction of growing pigs compared with colistin sulfate.…”

“…In addition to morphology measurements, jejunal antioxidant capacity and tight junction were also analysed to explore intestinal health of growing pigs . Under oxidative stress conditions, reactive oxygen species synthesis can trigger greater prevalence of pathogenic microorganisms as a result of compromised immune cell functions, which could subsequently lead to defects in gastrointestinal barrier function . The present study showed that there were no differences in activity of antioxidant enzyme and protein expression of occludin, claudin1 and claudin3 among pigs consuming colistin sulfate or lysozyme diets.…”

β1 Integrin regulates adult lung alveolar epithelial cell inflammation

“…In addition, claudin-18-null mice develop AEC hyperplasia and macrophage accumulation over time (89)(90)(91). Although a causal relationship between β 1 integrin and claudins has not been described, previous in vitro studies demonstrated that ROS can disrupt tight junctions (92)(93)(94), suggesting that β 1 integrin-mediated ROS could regulate tight junctions via effects on claudin expression. Another phenotype identified in β1 rtTA mice is AEC proliferation.…”