Mechanism-based alternative monitoring of endoplasmic reticulum stress by 8-keto-trichothecene mycotoxins using human intestinal epithelial cell line

Yang, Hyun; Park, Seong Hwan; Choi, Hye Jin; Hun, Kee; Kim, Juil; An, Tae-Jin; Lee, Soo Hyung; Moon, Yuseok

doi:10.1016/j.toxlet.2010.07.008

Cited by 12 publications

(11 citation statements)

References 43 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…XBP1 mRNA is induced by ATF6 and spliced by IRE1 in response to ER stress (Yoshida et al 2001), and ATF6 is required for optimal expression of GRP78 (Baumeister et al 2005). Our results thus indicate that PERK/ATF4, IRE1, and ATF6 arms of the UPR (Yang et al 2010;Su et al 2013). This suggests that induction of ER stress may be a common feature of mycotoxin toxicity.…”

Section: Discussionmentioning

confidence: 60%

Crocin and Quercetin protect HCT116 and HEK293 cells from Zearalenone-induced apoptosis by reducing endoplasmic reticulum stress

Salem

Prola

Boussabbeh

et al. 2015

Cell Stress and Chaperones

View full text Add to dashboard Cite

Mycotoxins are considered to be significant contaminants of food and animal feed. Zearalenone (ZEN) is a non-steroidal estrogenic mycotoxin produced by several species of Fusarium in cereals and agricultural products. ZEN has been shown to be cytotoxic, genotoxic, and mutagenic in different cell types. In the present study, we investigated the involvement of endoplasmic reticulum (ER) stress in ZENmediated toxicity in human intestine (HCT116) and kidney (HEK293) cells and evaluated the effects of the two common dietary compounds Quercetin (QUER) and Crocin (CRO). We show that ZEN treatment induces ER stress and activates the unfolded protein response (UPR) as evidenced by XBP1 mRNA splicing and upregulation of GRP78, ATF4, GADD34, PDIA6, and CHOP. Activation of the ER stress response is associated with activation of the mitochondrial pathway of apoptosis. This apoptotic process is characterized by an increase in ROS generation and lipid peroxidation, a loss of mitochondrial transmembrane potential (ΔΨm), and an activation of caspases and DNA damages. We also demonstrate that the antioxidant properties of QUER and CRO help to prevent ER stress and reduce ZEN-induced apoptosis in HCT116 and HEK293 cells. Our results suggest that antioxidant molecule might be helpful to prevent ZEN-induced ER stress and toxicity.

show abstract

Section: Discussionmentioning

confidence: 60%

Crocin and Quercetin protect HCT116 and HEK293 cells from Zearalenone-induced apoptosis by reducing endoplasmic reticulum stress

Salem

Prola

Boussabbeh

et al. 2015

Cell Stress and Chaperones

View full text Add to dashboard Cite

show abstract

“…Activated ribosomal proteins thus may induce ER stress-related responses, which are attenuated by deletion of ribosomes in yeast and human cells such as monocyte-derived cells and epithelial cells [2, 3, 53]. ER-disrupting environmental and genetic factors cause accumulation of misfolded and unfolded proteins in the ER lumen, a condition termed ER stress.…”

Section: Organellar Sentinels For Cytokine Induction: Ribosome and Ermentioning

confidence: 99%

Ribosomal Alteration-Derived Signals for Cytokine Induction in Mucosal and Systemic Inflammation: Noncanonical Pathways by Ribosomal Inactivation

Moon

2014

Mediators of Inflammation

Self Cite

View full text Add to dashboard Cite

Ribosomal inactivation damages 28S ribosomal RNA by interfering with its functioning during gene translation, leading to stress responses linked to a variety of inflammatory disease processes. Although the primary effect of ribosomal inactivation in cells is the functional inhibition of global protein synthesis, early responsive gene products including proinflammatory cytokines are exclusively induced by toxic stress in highly dividing tissues such as lymphoid tissue and epithelia. In the present study, ribosomal inactivation-related modulation of cytokine production was reviewed in leukocyte and epithelial pathogenesis models to characterize mechanistic evidence of ribosome-derived cytokine induction and its implications for potent therapeutic targets of mucosal and systemic inflammatory illness, particularly those triggered by organellar dysfunctions.

show abstract

“…ER stress induces calcium (Ca 2+ ) release in leukocytes—Ca 2+ -dependent calpain activation and subsequent pro-apoptotic caspase 8 activation [61]. Ribotoxic trichothecenes can also induce ER stress in gut epithelial cells, but it is not linked to cellular apoptosis [62]. Ribotoxin-induced epithelial ER stress mediates pro-inflammatory cytokine production instead of apoptosis [63], which may contribute to the disruption of epithelial tight junctions, as suggested in section 2.2.…”

Section: Mucosal Cell Death Due To Ribotoxic Stress and Epithelialmentioning

confidence: 99%

Mucosal Injuries due to Ribosome-Inactivating Stress and the Compensatory Responses of the Intestinal Epithelial Barrier

Moon

2011

Toxins

Self Cite

View full text Add to dashboard Cite

Ribosome-inactivating (ribotoxic) xenobiotics are capable of using cleavage and modification to damage 28S ribosomal RNA, which leads to translational arrest. The blockage of global protein synthesis predisposes rapidly dividing tissues, including gut epithelia, to damage from various pathogenic processes, including epithelial inflammation and carcinogenesis. In particular, mucosal exposure to ribotoxic stress triggers integrated processes that are important for barrier regulation and re-constitution to maintain gut homeostasis. In the present study, various experimental models of the mucosal barrier were evaluated for their response to acute and chronic exposure to ribotoxic agents. Specifically, this review focuses on the regulation of epithelial junctions, epithelial transporting systems, epithelial cytotoxicity, and compensatory responses to mucosal insults. The primary aim is to characterize the mechanisms associated with the intestinal epithelial responses induced by ribotoxic stress and to discuss the implications of ribotoxic stressors as chemical modulators of mucosa-associated diseases such as ulcerative colitis and epithelial cancers.

show abstract

Mechanism-based alternative monitoring of endoplasmic reticulum stress by 8-keto-trichothecene mycotoxins using human intestinal epithelial cell line

Cited by 12 publications

References 43 publications

Crocin and Quercetin protect HCT116 and HEK293 cells from Zearalenone-induced apoptosis by reducing endoplasmic reticulum stress

Crocin and Quercetin protect HCT116 and HEK293 cells from Zearalenone-induced apoptosis by reducing endoplasmic reticulum stress

Ribosomal Alteration-Derived Signals for Cytokine Induction in Mucosal and Systemic Inflammation: Noncanonical Pathways by Ribosomal Inactivation

Mucosal Injuries due to Ribosome-Inactivating Stress and the Compensatory Responses of the Intestinal Epithelial Barrier

Contact Info

Product

Resources

About