scholarly journals Vibrio vulnificus VvhA induces NF-κB-dependent mitochondrial cell death via lipid raft-mediated ROS production in intestinal epithelial cells

2015 ◽  
Vol 6 (2) ◽  
pp. e1655-e1655 ◽  
Author(s):  
S-J Lee ◽  
Y H Jung ◽  
S Y Oh ◽  
E J Song ◽  
S H Choi ◽  
...  
Keyword(s):  
Cell Death ◽  
Epithelial Cells ◽  
Lipid Raft ◽  
Vibrio Vulnificus ◽  
Intestinal Epithelial Cells ◽  
Ros Production ◽  
Intestinal Epithelial

scholarly journals Lipid rafts mediate internalization of β1-integrin in migrating intestinal epithelial cells

2008 ◽  
Vol 295 (5) ◽  
pp. G965-G976 ◽  
Author(s):  
Elena V. Vassilieva ◽  
Kirsten Gerner-Smidt ◽  
Andrei I. Ivanov ◽  
Asma Nusrat
Keyword(s):  
Epithelial Cells ◽  
Lipid Rafts ◽  
Lipid Raft ◽  
Intestinal Epithelial Cells ◽  
Focal Adhesions ◽  
Endocytic Pathway ◽  
Dependent Manner ◽  
Intestinal Epithelial ◽  
Caveolin 1 ◽  
Cell Matrix

Intestinal mucosal inflammation is associated with epithelial wounds that rapidly reseal by migration of intestinal epithelial cells (IECs). Cell migration involves cycles of cell-matrix adhesion/deadhesion that is mediated by dynamic turnover (assembly and disassembly) of integrin-based focal adhesions. Integrin endocytosis appears to be critical for deadhesion of motile cells. However, mechanisms of integrin internalization during remodeling of focal adhesions of migrating IECs are not understood. This study was designed to define the endocytic pathway that mediates internalization of β1-integrin in migrating model IECs. We observed that, in SK-CO15 and T84 colonic epithelial cells, β1-integrin is internalized in a dynamin-dependent manner. Pharmacological inhibition of clathrin-mediated endocytosis or macropinocytosis and small-interfering RNA (siRNA)-mediated knock down of clathrin did not prevent β1-integrin internalization. However, β1-integrin internalization was inhibited following cholesterol extraction and after overexpression of lipid raft protein, caveolin-1. Furthermore, internalized β1-integrin colocalized with the lipid rafts marker cholera toxin, and siRNA-mediated knockdown of caveolin-1 and flotillin-1/2 increased β1-integrin endocytosis. Our data suggest that, in migrating IEC, β1-integrin is internalized via a dynamin-dependent lipid raft-mediated pathway. Such endocytosis is likely to be important for disassembly of integrin-based cell-matrix adhesions and therefore in regulating IEC migration and wound closure.

Helicobacter hepaticusCytolethal Distending Toxin Causes Cell Death in Intestinal Epithelial Cells via Mitochondrial Apoptotic Pathway

Helicobacter ◽  
2010 ◽  
Vol 15 (2) ◽  
pp. 98-107 ◽  
Author(s):  
Namal P. M. Liyanage ◽  
Karoline C. Manthey ◽  
Rohana P. Dassanayake ◽  
Charles A. Kuszynski ◽  
Gregory G. Oakley ◽  
...  
Keyword(s):  
Cell Death ◽  
Epithelial Cells ◽  
Intestinal Epithelial Cells ◽  
Intestinal Epithelial ◽  
Apoptotic Pathway ◽  
Mitochondrial Apoptotic Pathway

Mucin 3 is involved in intestinal epithelial cell apoptosis viaN-(3-oxododecanoyl)-l-homoserine lactone-induced suppression of Akt phosphorylation

2014 ◽  
Vol 307 (2) ◽  
pp. C162-C168 ◽  
Author(s):  
Ryoko Taguchi ◽  
Shinya Tanaka ◽  
Ga-Hyun Joe ◽  
Hideaki Maseda ◽  
Nobuhiko Nomura ◽  
...  
Keyword(s):  
Cell Death ◽  
Epithelial Cells ◽  
Intestinal Epithelial Cells ◽  
Virulence Gene ◽  
Homoserine Lactone ◽  
Intestinal Epithelial ◽  
Cellular Functions ◽  
Virulence Gene Expression ◽  
Akt Phosphorylation ◽  
Epithelial Cell Apoptosis

N-acyl-homoserine lactones (AHL) are quorum-sensing molecules in bacteria that play important roles in regulating virulence gene expression in pathogens such as Pseudomonas aeruginosa. The present study compared responses between undifferentiated and differentiated Caco-2 cells to N-(3-oxododecanoyl)-l-homoserine lactone (3-oxo-C12-HSL). A low concentration of 3-oxo-C12-HSL (30 μM) is sufficient to reduce viability accompanied by apoptosis via the suppression of phosphorylation by Akt in undifferentiated Caco-2 cells. The suppression of Akt phosphorylation appears specific in 3-oxo-C12-HSL, because other AHLs did not influence the phosphorylation status of Akt. The reduced viability induced by 3-oxo-C12-HSL was partially recovered by constitutively active Akt overexpression in undifferentiated Caco-2 cells. Since mucin is considered a vital component of the gut barrier, we investigated whether mucin protects cellular functions induced by 3-oxo-C12-HSL in undifferentiated Caco-2 cells. The results showed that mucin protected undifferentiated Caco-2 cells from apoptosis induced by 3-oxo-C12-HSL. 3-Oxo-C12-HSL did not induce cell death in differentiated Caco-2 cells that expressed higher levels of mucin 3 (MUC3) than undifferentiated Caco-2 cells. In addition, 3-oxo-C12-HSL promoted cell death in undifferentiated Caco-2 cells transfected with MUC3 siRNA and reduced MUC3 expression in undifferentiated Caco-2 cells. Therefore, MUC3 might be responsible for the survival of undifferentiated intestinal epithelial cells in the presence of 3-oxo-C12-HSL through regulating Akt phosphorylation. In conclusion, 3-oxo-C12-HSL might influence the survival of undifferentiated intestinal epithelial cells as well as interactions between these cells and pathogens.

Morphogenic protein epimorphin protects intestinal epithelial cells from oxidative stress by the activation of EGF receptor and MEK/ERK, PI3 kinase/Akt signals

2007 ◽  
Vol 292 (1) ◽  
pp. G39-G52 ◽  
Author(s):  
Masahiro Iizuka ◽  
Kenji Sasaki ◽  
Yohei Hirai ◽  
Kenichi Shindo ◽  
Shiho Konno ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Hydrogen Peroxide ◽  
Cell Death ◽  
Epithelial Cells ◽  
Egf Receptor ◽  
Intestinal Epithelial Cells ◽  
Pi3 Kinase ◽  
Intestinal Epithelial ◽  
Extracellular Signal Regulated Kinase ◽  
Extracellular Signal

Epimorphin is a mesenchymal protein that regulates morphogenesis of epithelial cells. Our preliminary study suggested a novel function of epimorphin in enhancing survival of intestinal epithelial cells (IEC). Oxidative stress leads to cell injury and death and is suggested to be a key contributor to pathogenesis of inflammatory bowel disease. This study was conducted to determine whether epimorphin protects IEC from oxidative stress. Rat intestinal epithelial cell line IEC-6 was cultured with epimorphin (10 and 20 μg/ml), and the life span of IEC was assessed. The mean life span of IEC-6 cells was prolonged 1.9-fold ( P < 0.0006) by treatment with epimorphin. We then examined the epimorphin signaling pathways. Epimorphin phosphorylated epidermal growth factor (EGF) receptor, activated the MEK/extracellular signal-regulated kinase 1/2 mitogen-activated protein kinase and phosphatidylinositol 3 (PI3) kinase/Akt pathways, phosphorylated Bad, and induced Bcl-XL and survivin. Hydrogen peroxide (1 mM) induced cell death in 92% of IEC-6 cells, but epimorphin dramatically diminished (88.7%) cell death induced by hydrogen peroxide ( P < 0.0001). This protective effect of epimorphin was significantly attenuated by inhibitors of MEK and PI3 kinase ( P < 0.0001) or EGF receptor-neutralizing antibody ( P = 0.0007). In wound assays, the number of migrated cells in the wound area decreased (72.5%) by treatment with 30 μM hydrogen peroxide, but epimorphin increased the number of migrated cells 3.18-fold ( P < 0.0001). These results support a novel function of epimorphin in protecting IEC from oxidative stress. This anti-oxidative function of epimorphin is dramatic and is likely mediated by the activation of EGF receptors and the MEK/extracellular signal-regulated kinase and PI3 kinase/Akt signaling pathways and through the induction of anti-apoptotic factors.

scholarly journals Caspase-mediated cleavage of murine norovirus NS1/2 potentiates apoptosis and is required for persistent infection of intestinal epithelial cells

2018 ◽  
Author(s):  
Bridget A. Robinson ◽  
Jacob A. Van Winkle ◽  
Broc T McCune ◽  
A. Mack Peters ◽  
Timothy J. Nice
Keyword(s):  
Cell Death ◽  
Epithelial Cells ◽  
Persistent Infection ◽  
Acute Gastroenteritis ◽  
Intestinal Epithelial Cells ◽  
Intestinal Epithelial ◽  
Murine Norovirus ◽  
Structural Protein ◽  
Human Norovirus ◽  
Caspase Cleavage

AbstractHuman norovirus (HNoV) is the leading cause of acute gastroenteritis and is spread by fecal shedding that can often persist for weeks to months after the resolution of symptoms. Elimination of persistent viral reservoirs has the potential to prevent outbreaks. Similar to HNoV, murine norovirus (MNV) is spread by persistent shedding in the feces and provides a tractable model to study molecular mechanisms of enteric persistence. Previous studies have identified non-structural protein 1 (NS1) from the persistent MNV strain CR6 as critical for persistent infection in intestinal epithelial cells (IECs), but its mechanism of action remains unclear. We now find that the function of CR6 NS1 is regulated by apoptotic caspase cleavage. Following induction of apoptosis in infected cells, caspases cleave the precursor NS1/2 protein, and this cleavage is prevented by mutation of caspase target motifs. These mutations profoundly compromise CR6 infection of IECs and persistence in the intestine. Conversely, NS1/2 cleavage is not required for acute replication in extra-intestinal tissues or in cultured myeloid cells, indicating an IEC-specific role. Intriguingly, we find that caspase cleavage of NS1/2 reciprocally promotes caspase activity, potentiates cell death, and amplifies spread among cultured IEC monolayers. Together, these data indicate that the function of CR6 NS1 is regulated by apoptotic caspases, and suggest that apoptotic cell death enables epithelial spread and persistent shedding.Author SummaryHuman Norovirus infection is highly contagious and the most common cause of acute gastroenteritis. Norovirus can be persistently shed after resolution of symptoms, perpetuating or initiating new outbreaks. Murine norovirus (MNV) is also persistently shed, enabling study of host and viral determinants of norovirus pathogenesis. We previously identified a critical role for MNV non-structural protein 1 (NS1), in persistence. Herein we find that regulation of NS1 by host apoptotic caspases is required for infection of intestinal epithelial cells, but not for extra-intestinal spread. Additionally, we demonstrate that NS1 reciprocally promotes cell death and spread among epithelial cells. These data identify regulation of NS1 by host proteases and suggest that apoptotic death is a determinant of epithelial spread and persistence.

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