Signaling through C/EBP Homologous Protein and Death Receptor 5 and Calpain Activation Differentially Regulate THP-1 Cell Maturation-Dependent Apoptosis Induced by Shiga Toxin Type 1

Lee, Moo‐Seung; Cherla, Rama P.; Lentz, Erin K.; Leyva‐Illades, Dinorah; Tesh, Vernon L.

doi:10.1128/iai.00342-10

Cited by 22 publications

(21 citation statements)

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“…We have also reported that Stx1 treatment of differentiated THP-1 cells led to the increased expression of the apoptosis-inducing factor TRAIL and its receptor DR5 (TRAIL-R2). Signaling through TRAIL-DR5 engagement and the activation of calpains may contribute to the cleavage of procaspase-8 that we detected in Stx-treated THP-1 cells (Lee et al , 2010). …”

Section: Discussionmentioning

confidence: 77%

“…We previously showed that Stxs induced calpain activation (cleavage) in D-THP-1 cells and calpains contributed to apoptosis (Lee et al , 2008, Lee et al, 2010). Treatment of HK-2 cells with Stx-2 led to a dose-dependent increase in levels of 28 kDa cleaved calpain fragments 24 h after intoxication (Figure 7A).…”

Section: Resultsmentioning

confidence: 99%

“…Once in the cytoplasm, the A 1 -fragment escapes routing to the proteasome and inhibits protein synthesis by the catalytic removal of a single adenine residue from the 28S rRNA (reviewed in Johannes and Römer, 2010; Sandvig et al ., 2010). In addition to mediating protein synthesis inhibition, Stxs activate multiple signaling pathways including: i) signaling through src kinases, PI3K, Akt and mTOR (Katagiri et al , 1999, Zanchi et al , 2008, Cherla et al , 2009); ii) activation of MAPKs (Foster et al , 2002, Smith et al , 2003) and their upstream kinases PKR, MK-2 and ZAK (Gray et al , 2008, Jandhyala et al , 2008, Saenz et al , 2009); iii) activation of NF-κB and AP-1 transcription factors (Sakiri et al , 1998, Zoja et al, 2002); and iv) prolonged activation of the ER stress response (Lee et al , 2009, Lee et al , 2010). Signaling through these pathways has been shown to be important in toxin internalization and routing, induction of cytokine/chemokine expression, and the induction of apoptosis.…”

Section: Discussionmentioning

confidence: 99%

“…Thus, autophagy plays a critical role in the decision of cellular fate (Hoyer-Hansen et al , 2007, Moretti et al , 2007). While we have reported that Stxs activate apoptotic signaling pathways through the induction of ER stress and signaling through TRAIL and the apoptosis-inducing receptor DR5 (TRAIL-R2) in macrophage-like THP-1 cells, (Lee et al , 2008, Lee et al , 2010), few studies have been carried out to examine the capacity of the toxins to activate autophagy, and it is currently unknown if autophagy contributes to, or protects cells from, Stx-induced apoptosis. It is interesting to note, however, that signaling through DR5 and caspase-8 is also known to activate autophagy contributing to cell death (Park et al , 2009, Norman et al , 2010).…”

Section: Introductionmentioning

confidence: 99%

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Shiga toxins induce autophagy leading to differential signalling pathways in toxin-sensitive and toxin-resistant human cells

Lee¹,

Cherla²,

Jenson³

et al. 2011

Cellular Microbiology

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Summary The bacterial virulence factors Shiga toxins (Stxs) are expressed by Shigella dysenteriae serotype 1 and certain Escherichia coli strains. Stxs are protein synthesis inhibitors and induce apoptosis in many cell types. Stxs induce apoptosis via prolonged ER stress signaling to activate both extrinsic and intrinsic pathways in human myeloid cells. Studies have shown that autophagy, a lysosome-dependent catabolic process, may be associated with activation of pro-survival or death processes. It is currently unknown if autophagy contributes to apoptosis or protects cells from Stxs. To study cellular responses to Stxs, we intoxicated toxin-sensitive cells (THP-1 and HK-2 cells), and toxin-resistant cells (primary human monocyte-derived macrophages) and examined toxin intracellular trafficking and autophagosome formation. Stxs translocated to different cell compartments in toxin-resistant versus toxin-sensitive cells. Confocal microscopy revealed autophagosome formation in both toxin-resistant and toxin-sensitive cells. Proteolytic cleavage of Atg5 and Beclin-1 play pivotal roles in switching non-cytotoxic autophagy to cell death signaling. We detected cleaved forms of Atg5 and Beclin-1 in Stx-treated toxin-sensitive cells, while cleaved caspases, calpains, Atg5 and Beclin-1 were not detected in toxin-resistant primary human monocytes and macrophages. These findings suggest that toxin sensitivity correlates with caspase and calpain activation, leading to Atg5 and Beclin-1 cleavage.

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Section: Discussionmentioning

confidence: 77%

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Shiga toxins induce autophagy leading to differential signalling pathways in toxin-sensitive and toxin-resistant human cells

Lee¹,

Cherla²,

Jenson³

et al. 2011

Cellular Microbiology

Self Cite

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“…Stxs also activate the ER stress response, which is normally triggered by the accumulation of misfolded proteins within the ER (18). Prolonged activation of ER stress is associated with the induction of apoptosis (18,19). Although the stress responses activated by Stxs appear to be cell type specific, the maturation state of a given cell may determine its cellular response to intoxication.…”

mentioning

confidence: 99%

Shiga Toxins Activate the NLRP3 Inflammasome Pathway To Promote Both Production of the Proinflammatory Cytokine Interleukin-1β and Apoptotic Cell Death

et al. 2016

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Natural Compound Licochalcone B Induced Extrinsic and Intrinsic Apoptosis in Human Skin Melanoma (A375) and Squamous Cell Carcinoma (A431) Cells

Kang

Yoon

Kang

et al. 2017

Phytotherapy Research

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Licochalcone B (Lico B), which is normally isolated from the roots of Glycyrrhiza inflata (Chinese Licorice), generally classified into organic compounds including retrochalcones. Potential pharmacological properties of Lico B include anti-inflammatory, anti-bacterial, anti-oxidant, and anti-cancer activities. However, its biological effects on melanoma and squamous cell carcinoma (SCC) are unknown. Based on these known facts, this study investigated the role of Lico B in apoptosis, through the extrinsic and intrinsic pathways and additional regulation of specificity protein 1 in human skin cancer cell lines. Annexin V/7-aminoactinomycin D staining, western blot analysis, mitochondrial membrane potential assay, and an anchorage-independent cell transformation assay demonstrated that Lico B treatment of human melanoma and SCC cells significantly inhibited cell proliferation and induced apoptotic cell death. More specifically, Lico B induced apoptosis through the regulation of specificity protein 1 and apoptosis-related proteins including CCAAT/enhancer-binding protein homologous protein, death receptors, and poly (ADP-ribose) polymerase. These results indicate that Lico B has apoptotic effect on A375 and A431 skin cancer cells, suggesting the potential value of Lico B for the treatment of human melanoma and SCC. Copyright © 2017 John Wiley & Sons, Ltd.

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Signaling through C/EBP Homologous Protein and Death Receptor 5 and Calpain Activation Differentially Regulate THP-1 Cell Maturation-Dependent Apoptosis Induced by Shiga Toxin Type 1

Cited by 22 publications

References 65 publications

Shiga toxins induce autophagy leading to differential signalling pathways in toxin-sensitive and toxin-resistant human cells

Shiga toxins induce autophagy leading to differential signalling pathways in toxin-sensitive and toxin-resistant human cells

Shiga Toxins Activate the NLRP3 Inflammasome Pathway To Promote Both Production of the Proinflammatory Cytokine Interleukin-1β and Apoptotic Cell Death

Natural Compound Licochalcone B Induced Extrinsic and Intrinsic Apoptosis in Human Skin Melanoma (A375) and Squamous Cell Carcinoma (A431) Cells

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