Tunicamycin-induced Endoplasmic Reticulum Stress Upregulates the Expression of Pentraxin 3 in Human Retinal Pigment Epithelial Cells

Hwang, Narae; Kwon, Mi Young; Bong, Jae; Chung, Sung Min; Woo, Je Moon

doi:10.3341/kjo.2016.30.6.468

Cited by 11 publications

(8 citation statements)

References 54 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We assumed that the reduced cell metabolic activity was a consequence of a reduced cell viability, as it has been observed in other studies. 38,39 LDH release corroborated it ( Figure 1B). Besides, these observations were validated by flow cytometric analysis ( Figure 1C).…”

Section: Tnfα Induced Cell Death Through Activation Of Caspases (3supporting

confidence: 66%

“…Tunicamycin, an inducer of unfolded protein response, induced cell death by promoting caspase 3 activation as occurs in other retinal cells such as ARPE-19, or primary culture of retinal ganglion cells. 39,73 In this case, ADA did not prevent from cell death suggesting other key players responsible for cell death. Besides, tunicamycin induced TNFα upregulation, downregulation of TNFR1, and perinuclear accumulation of PAR polymers.…”

Section: A Single Dose Of Intravitreal Adalimumab Reduced Nlrp3 Infmentioning

confidence: 69%

“…Tunicamycin toxicity is well established. 39 We selected 10 μg/µL for tunicamycin to evaluate the effect of ADA on the mechanism of the tunicamycin-mediated cell death. After 24 hours, the treatment with tunicamycin (10 µg/ µL) upregulated TNFα (TNFα release and TNFα gene expression) and downregulated TNFR1 (gene expression) in a dose-dependent manner (Kruskal-Wallis test, Dunn test multiple comparisons).…”

mentioning

confidence: 99%

See 2 more Smart Citations

Intravitreal administration of adalimumab delays retinal degeneration in rd10 mice

et al. 2020

View full text Add to dashboard Cite

Retinitis pigmentosa (RP) is a group of inherited retinal dystrophies characterized by the progressive and irreversible loss of vision. We previously found that intraperitoneal administration of Adalimumab, a monoclonal anti‐TNFα antibody, slowed down retinal degeneration in the murine model of RP, the rd10 mice. The aims of this study were to improve its neuroprotective effect and to deepen understanding of the molecular mechanisms involved in this effect. We analyzed (i) the in vitro effect of Adalimumab on the TNFα‐mediated cell death in retinal cells; (ii) the effect of a single intravitreal injection of Adalimumab on retinal degeneration in rd10 mice at postnatal day (P) 23. In vitro studies showed that TNFα induced caspase and poly ADP ribose polymerase (PARP) activation, downregulation of (kinase receptor‐interacting protein 1) RIPK1 and upregulation of RIPK3 in retinal cells. Adalimumab reduced cell death probably through the inhibition of caspase 3 activation. In vivo studies suggested that PARP and NLRP3 inflammasome are mainly activated and to a lesser extent caspase‐dependent mechanisms in rd10 retinas at P23. Necroptosis seems to be inhibited by the downregulation of RIPK1. Adalimumab prevented from retinal degeneration without affecting caspase ‐dependent mechanisms but decreasing PARP activation, microglia activation as well as NLRP3 inflammasome.

show abstract

Section: Tnfα Induced Cell Death Through Activation Of Caspases (3supporting

confidence: 66%

Section: A Single Dose Of Intravitreal Adalimumab Reduced Nlrp3 Infmentioning

confidence: 69%

mentioning

confidence: 99%

See 1 more Smart Citation

Intravitreal administration of adalimumab delays retinal degeneration in rd10 mice

et al. 2020

View full text Add to dashboard Cite

show abstract

“…Both IL-6 and IL-23 are secreted via the constitutive secretory pathway. ER stress was shown also to increase the secretion of pentraxin 3 from ARPE-19 human retinal pigment epithelial cells (Hwang et al 2016) and the secretion of prostate apoptosis response-4 (Par-4) protein from PC-3 prostate cancer cells (Burikhanov et al 2009). Finally, the secretion of vascular endothelial growth factor (VEGF) from several human tumor cell lines was shown to increase during ER stress induced by glucose deprivation, thapsigargin, or tunicamycin (Wang et al 2012).…”

Section: Argument Against Inhibition Of Er Export By Er Stressmentioning

confidence: 99%

Effect of the unfolded protein response on ER protein export: a potential new mechanism to relieve ER stress

Shaheen¹

2018

Cell Stress and Chaperones

View full text Add to dashboard Cite

The unfolded protein response (UPR) is an adaptive cellular response that aims to relieve endoplasmic reticulum (ER) stress via several mechanisms, including inhibition of protein synthesis and enhancement of protein folding and degradation. There is a controversy over the effect of the UPR on ER protein export. While some investigators suggested that ER export is inhibited during ER stress, others suggested the opposite. In this article, their conflicting studies are analyzed and compared in attempt to solve this controversy. The UPR appears indeed to enhance ER export, possibly via multiple mechanisms. However, another factor, which is the integrity of the folding machinery/environment inside ER, determines whether ER export will appear increased or decreased during experimentation. Also, different methods of stress induction appear to have different effects on ER export. Thus, improvement of ER export may represent a new mechanism by which the UPR alleviates ER stress. This may help researchers to understand how the UPR works inside cells and how to manipulate it to alter cell fate during stress, either to promote cell survival or death. This may open up new approaches for the treatment of ER stress-related diseases.

show abstract

“…BEZ235 is a dual PI3K/mTOR inhibitor that can reverse resistance to CDDP [ 15 ]. Tunicamycin acts as an antibiotic that suppresses the intracellular production of N-linked glycans and can be used to induce ERS [ 16 , 17 ]. Although previous studies have suggested that ERS was highly induced in various tumors and correlated with cancer cell survival and resistance to anti-cancer treatments [ 18 , 19 ], few studies have explored the effect of ERS on human ovarian cancer cells.…”

Section: Introductionmentioning

confidence: 99%

Endoplasmic reticulum stress promotes autophagy and apoptosis and reverses chemoresistance in human ovarian cancer cells

Guo

et al. 2017

Oncotarget

View full text Add to dashboard Cite

Ovarian cancer presents the highest mortality rate among gynecological tumors. Here, we measured cell viability, proliferation, apoptosis, autophagy, and expression of endoplasmic reticulum stress (ERS)-related proteins, PI3K/AKT/mTOR pathway-related proteins, and apoptosis- and autophagy-related proteins in SKOV3 and SKOV3/CDDP cells treated with combinations of CDDP, tunicamycin, and BEZ235 (blank control, CDDP, CDDP + tunicamycin, CDDP + BEZ235, and CDDP + tunicamycin + BEZ235). Increasing concentrations of tunicamycin and CDDP activated ERS in SKOV3 cells, reduced cell viability and proliferation, increased apoptosis and autophagy, enhanced expression of ERS-related proteins, and inhibited expression of PI3K/AKT/mTOR pathway-related proteins. CDDP, tunicamycin, and BEZ235 acted synergistically to enhance these effects. We also detected lower expression of the ERS-related proteins caspase-3, LC3 II and Beclin 1 in ovarian cancer tissues than adjacent normal tissues. By contrast, expression of Bcl-2 and PI3K/AKT/mTOR pathway-related proteins was higher in ovarian cancer tissues than adjacent normal tissues. Lastly, expression of the ERS-related proteins Beclin 1, caspase-3 and LC3 II was higher in the sensitive group than the resistant group, while expression of Bcl-2, LC3 I, P62 and PI3K/AKT/mTOR pathway-related proteins was decreased. These results show that ERS promotes cell autophagy and apoptosis while reversing chemoresistance in ovarian cancer cells by inhibiting activation of the PI3K/AKT/mTOR signaling pathway.

show abstract

Tunicamycin-induced Endoplasmic Reticulum Stress Upregulates the Expression of Pentraxin 3 in Human Retinal Pigment Epithelial Cells

Cited by 11 publications

References 54 publications

Intravitreal administration of adalimumab delays retinal degeneration in rd10 mice

Intravitreal administration of adalimumab delays retinal degeneration in rd10 mice

Effect of the unfolded protein response on ER protein export: a potential new mechanism to relieve ER stress

Endoplasmic reticulum stress promotes autophagy and apoptosis and reverses chemoresistance in human ovarian cancer cells

Contact Info

Product

Resources

About