ER signaling regulation drives the switch between autophagy and apoptosis in NRK-52E cells exposed to cisplatin

Rovetta, Francesca; Stacchiotti, Alessandra; Consiglio, Antonella; Cadei, Moris; Grigolato, Pier Giovanni; Llombart‐Bosch, Antonio; Rezzani, Rita; Aleo, Maria Francesca

doi:10.1016/j.yexcr.2011.11.008

Cited by 49 publications

(38 citation statements)

References 43 publications

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“…In response to ER stress, XBP1 mRNA undergoes unconventional splicing through IRE1␣, giving rise to a spliced form (17,18). A number of previous reports have already highlighted the link of ER stress response with the induction of autophagy (31)(32)(33)(34). For instance, Yorimitsu et al (35) have shown that ER stress induces autophagy, which can protect against cell death.…”

Section: Discussionmentioning

confidence: 99%

XBP1 mRNA Splicing Triggers an Autophagic Response in Endothelial Cells through BECLIN-1 Transcriptional Activation

Margariti

Chen

et al. 2013

Journal of Biological Chemistry

250

164

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Background: Apoptosis and autophagy are two closely related systems that induce cell death. Results: X-box-binding protein 1 (XBP1) mRNA splicing regulates BECLIN-1 transcriptional activation, a fundamental player in the initiation of autophagy. Conclusion: XBP1 splicing induces an autophagic response in endothelial cells. Significance: XBP1 could be used as an important pharmacological target that can regulate the autophagic machinery and endothelial cell death.

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Section: Discussionmentioning

confidence: 99%

XBP1 mRNA Splicing Triggers an Autophagic Response in Endothelial Cells through BECLIN-1 Transcriptional Activation

Margariti

Chen

et al. 2013

Journal of Biological Chemistry

250

164

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“…GRP78 is an important resident chaperone that maintains cellular homeostasis by ensuring the proper folding of protein in the ER (Rovetta et al 2012), whereas, CHOP is a pro-apoptotic protein, which is induced by all the three arms of UPR-ATF6, IRE1, and PERK pathways (Katsoulieris et al 2010). Our results confirmed the ability of TM (at 0.5 μg/mL for 2 h) to induce ER stress (marked by the induction of GRP78 and CHOP), and cell death (evidenced by~60% reduction in cell viability) in NRK-52E cells.…”

Section: Discussionmentioning

confidence: 99%

Structure–activity relationship of piperine and its synthetic amide analogs for therapeutic potential to prevent experimentally induced ER stress in vitro

Hammad

Ravindran

Khalil

et al. 2017

Cell Stress and Chaperones

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Endoplasmic reticulum (ER) is the key organelle involved in protein folding and maturation. Emerging studies implicate the role of ER stress in the development of chronic kidney disease. Thus, there is an urgent need for compounds that could ameliorate ER stress and prevent CKD. Piperine and its analogs have been reported to exhibit multiple pharmacological activities; however, their efficacy against ER stress in kidney cells has not been studied yet. Hence, the goal of this study was to synthesize amide-substituted piperine analogs and screen them for pharmacological activity to relieve ER stress using an in vitro model of tunicamycininduced ER stress using normal rat kidney (NRK-52E) cells. Five amide-substituted piperine analogs were synthesized and their chemical structures were elucidated by pertinent spectroscopic techniques. An in vitro model of ER stress was developed using tunicamycin, and the compounds of interest were screened for their effect on cell viability, and the expression of ER chaperone GRP78, the pro-apoptotic ER stress marker CHOP, and apoptotic caspases 3 and 12 (via western blotting). Our findings indicate that exposure to tunicamycin (0.5 μg/ mL) for 2 h induces the expression of GRP78 and CHOP, and apoptotic markers (caspase-3 and caspase-12) and causes a significant reduction in renal cell viability. Pre-treatment of cells with piperine and its cyclohexylamino analog decreased the tunicamycin-induced upregulation of GRP78 and CHOP and cell death. Taken together, our findings demonstrate that piperine and its analogs differentially regulate ER stress, and thus represent potential therapeutic agents to treat ER stressrelated renal disorders.

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“…This finding suggests that the linkage between autophagy signaling and death signals may be located upstream in the process of autophagy, as the targets of 3-MA were located at the initiation of autophagy. In fact, ER itself can function as a switching point in autophagy and death by interaction between Bcl-2 family proteins occurring on the ER membrane (50,51).…”

Section: Discussionmentioning

confidence: 99%

Enhanced autophagic flux by endoplasmic reticulum stress in human hepatocellular carcinoma cells contributes to the maintenance of cell viability

Zhu

et al. 2013

Oncology Reports

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Abstract. Endoplasmic reticulum (ER) stress and autophagy are important adaptive responses in eukaryotes. The aim of this study was to investigate the autophagic responses in hepatocellular carcinoma (HCC) cells under ER stress and the effect of autophagy on cell survival and death. The human HCC cell line HepG2 was stimulated with tunicamycin to induce ER stress. Cell viability was detected using the Cell Counting Kit-8. The accumulation of autophagic compartments was observed using transmission electron microscopy. The expression of ER and autophagy-related proteins was assessed by western blotting. Autophagic flux was assessed by microtubule-associated protein 1-light chain 3 (MAP1-LC3) turnover assay in the presence of chloroquine to inhibit lysosomes. HepG2 cells subjected to the ER stress presented a significant accumulation of autophagosomes and increased conversion of LC3-I to LC3-II as well as enhanced autophagic flux as detected by the LC3 turnover assay. Inhibition of autophagy with 3-methyladenine facilitated ER stress-related cell death. We conclude that ER stress enhances the autophagic flux in HepG2 cells, which may contribute to the maintenance of cell viability.

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ER signaling regulation drives the switch between autophagy and apoptosis in NRK-52E cells exposed to cisplatin

Cited by 49 publications

References 43 publications

XBP1 mRNA Splicing Triggers an Autophagic Response in Endothelial Cells through BECLIN-1 Transcriptional Activation

XBP1 mRNA Splicing Triggers an Autophagic Response in Endothelial Cells through BECLIN-1 Transcriptional Activation

Structure–activity relationship of piperine and its synthetic amide analogs for therapeutic potential to prevent experimentally induced ER stress in vitro

Enhanced autophagic flux by endoplasmic reticulum stress in human hepatocellular carcinoma cells contributes to the maintenance of cell viability

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