Reactive Oxygen Species (ROS), Nanoparticles, and Endoplasmic Reticulum (ER) Stress-Induced Cell Death Mechanisms

2020 ◽  
Keyword(s):  
Reactive Oxygen Species ◽  
Endoplasmic Reticulum ◽  
Cell Death ◽  
Er Stress ◽  
Reactive Oxygen ◽  
Oxygen Species ◽  
Cell Death Mechanisms

scholarly journals Gadd153 Sensitizes Cells to Endoplasmic Reticulum Stress by Down-Regulating Bcl2 and Perturbing the Cellular Redox State

2001 ◽  
Vol 21 (4) ◽  
pp. 1249-1259 ◽  
Author(s):  
Karen D. McCullough ◽  
Jennifer L. Martindale ◽  
Lars-Oliver Klotz ◽  
Tak-Yee Aw ◽  
Nikki J. Holbrook
Keyword(s):  
Reactive Oxygen Species ◽  
Endoplasmic Reticulum ◽  
Cell Death ◽  
Er Stress ◽  
Cell Lines ◽  
Reactive Oxygen ◽  
Oxygen Species ◽  
Down Regulation ◽  
Gadd153 Expression ◽  
Bcl2 Expression

ABSTRACT gadd153, also known as chop, is a highly stress-inducible gene that is robustly expressed following disruption of homeostasis in the endoplasmic reticulum (ER) (so-called ER stress). Although all reported types of ER stress induce expression of Gadd153, its role in the stress response has remained largely undefined. Several studies have correlated Gadd153 expression with cell death, but a mechanistic link between Gadd153 and apoptosis has never been demonstrated. To address this issue we employed a cell model system in which Gadd153 is constitutively overexpressed, as well as two cell lines in which Gadd153 expression is conditional. In all cell lines, overexpression of Gadd153 sensitized cells to ER stress. Investigation of the mechanisms contributing to this effect revealed that elevated Gadd153 expression results in the down-regulation of Bcl2 expression, depletion of cellular glutathione, and exaggerated production of reactive oxygen species. Restoration of Bcl2 expression in Gadd153-overexpressing cells led to replenishment of glutathione and a reduction in levels of reactive oxygen species, and it protected cells from ER stress-induced cell death. We conclude that Gadd153 sensitizes cells to ER stress through mechanisms that involve down-regulation of Bcl2 and enhanced oxidant injury.

scholarly journals Selective Activation of Endoplasmic Reticulum Stress by Reactive-Oxygen-Species-Mediated Ochratoxin A-Induced Apoptosis in Tubular Epithelial Cells

2021 ◽  
Vol 22 (20) ◽  
pp. 10951
Author(s):  
Chong-Sun Khoi ◽  
Yu-Wen Lin ◽  
Jia-Huang Chen ◽  
Biing-Hui Liu ◽  
Tzu-Yu Lin ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Endoplasmic Reticulum ◽  
Er Stress ◽  
Ochratoxin A ◽  
Reactive Oxygen ◽  
Underlying Mechanism ◽  
Oxygen Species ◽  
Food And Feed ◽  
Renal Proximal Tubular Cells ◽  
Induced Apoptosis

Ochratoxin A (OTA), one of the major food-borne mycotoxins, impacts the health of humans and livestock by contaminating food and feed. However, the underlying mechanism of OTA nephrotoxicity remains unknown. This study demonstrated that OTA induced apoptosis through selective endoplasmic reticulum (ER) stress activation in human renal proximal tubular cells (HK-2). OTA increased ER-stress-related JNK and precursor caspase-4 cleavage apoptotic pathways. Further study revealed that OTA increased reactive oxygen species (ROS) levels, and N-acetyl cysteine (NAC) could reduce OTA-induced JNK-related apoptosis and ROS levels in HK-2 cells. Our results demonstrate that OTA induced ER stress-related apoptosis through an ROS-mediated pathway. This study provides new evidence to clarify the mechanism of OTA-induced nephrotoxicity.

scholarly journals Reactive oxygen species mediate anlotinib-induced apoptosis via activation of endoplasmic reticulum stress in pancreatic cancer

2020 ◽  
Vol 11 (9) ◽  
Author(s):  
Liguo Yang ◽  
Xiaoshu Zhou ◽  
Jinrui Sun ◽  
Qianghui Lei ◽  
Qi Wang ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Pancreatic Cancer ◽  
Endoplasmic Reticulum ◽  
Er Stress ◽  
Cell Lines ◽  
Reactive Oxygen ◽  
Oxygen Species ◽  
Antitumour Effect ◽  
Apoptotic Effect

Abstract Anlotinib (AL3818), a novel multi-targeted receptor tyrosine kinase inhibitor, has recently been proven to be an antitumour drug. This study aimed to explore the antitumour effect of anlotinib and its underlying molecular mechanisms in human pancreatic cancer (PC) cells. The anti-proliferative effect of anlotinib for three PC cell lines was validated using CCK-8, colony formation and EdU detection assays. Cell cycle, cell apoptosis, and reactive oxygen species (ROS) detection assays, a PC xenograft model and immunohistochemistry were performed to elucidate the mechanisms by which anlotinib induced tumour lethality in vitro and in vivo. These results demonstrated that anlotinib inhibited proliferation, induced G2/M phase arrest and triggered apoptosis in PC cell lines. Anlotinib induced PC’s apoptosis through the accumulation of ROS which activated the endoplasmic reticulum (ER) stress via PERK/p-eIF2α/ATF4 pathway. Furthermore, we demonstrated that the expression level of Nrf2, an antioxidant protein, increased with anlotinib treatment. Nrf2 knockdown enhanced the pro-apoptotic effect of anlotinib and the expression of the PERK/p-eIF2α/ATF4 pathway. The in vivo results suggested that suppressing Nrf2 improved the antitumour effect of anlotinib on PC cells. These data indicated that the apoptotic effect of anlotinib on PC cells was induced by ER stress via the accumulation of ROS. In the future, anlotinib combined with an Nrf2 inhibitor may provide a new therapeutic strategy for the treatment of human PC.

47 Inhibition of endoplasmic reticulum stress during invitro maturation improves the developmental competence of bovine cumulus-oocyte complexes

2020 ◽  
Vol 32 (2) ◽  
pp. 149
Author(s):  
H. Khatun ◽  
Y. Ihara ◽  
K. Takakura ◽  
Y. Wada ◽  
K.-I. Yamanaka
Keyword(s):  
Reactive Oxygen Species ◽  
Endoplasmic Reticulum ◽  
Embryonic Development ◽  
Er Stress ◽  
Mrna Expression ◽  
Reactive Oxygen ◽  
Developmental Competence ◽  
Apoptotic Cells ◽  
Oxygen Species ◽  
Maturation Rate

Endoplasmic reticulum (ER) stress, a dysfunction in protein-folding capacity of ER, is involved in many physiological responses including embryonic development. Evidence shows that the ER stress-induced unfolded protein response signaling pathway is associated with impairment of oocyte maturation and pre-implantation embryonic development; supplementation of culture medium with tauroursodeoxycholic acid (TUDCA), an ER stress inhibitor, improved the developmental process of oocytes and embryos by attenuating ER stress. However, no reports are available on the role of TUDCA in reducing ER stress during IVM of bovine oocytes. Therefore, the aim of this study was to examine the mechanism of TUDCA on reducing ER stress in maturation of bovine cumulus-oocyte complexes (COCs) and whether inhibition of ER stress during maturation can promote subsequent embryonic development. Bovine ovaries were collected from a local slaughterhouse, and after aspiration COCs were matured with/without TUDCA (50, 100, and 200 µM) for 22h at 38.5°C in a humidified atmosphere of 5% CO2. After IVM, we examined the maturation rate, reactive oxygen species, apoptosis, protein/mRNA expression levels, and subsequent embryonic development after IVF. The data were analysed using analysis of variance followed by the Tukey-Kramer multiple comparison test. As a result, the dose-dependent experiment shows that a 100μM concentration of TUDCA significantly increased the maturation rate and decreased the percentage of apoptotic cells in COCs and reactive oxygen species levels in denuded oocytes. Subsequently, the expression of ER stress inducible protein GRP78/BIP significantly decreased in COCs treated with 100 µM TUDCA compared with the control COCs. In addition, the mRNA expression of ER stress and pro-apoptotic markers (GRP78/BIP, PERK, IER1, ATF4, XBP1, CHOP, and BAX) in COCs were significantly decreased by TUDCA (100 µM) treatment, whereas it increased anti-apoptotic BCL2 expression. Moreover, we show that TUDCA (100 µM) supplementation enhances embryonic development by significantly increasing the blastocyst formation rate (43.6±1.8% vs. 49.7±1.3%) and decreasing the number of apoptotic cells (7.7±1.1% vs. 5.03±0.6%) in blastocysts. These findings suggest that existence of ER stress during maturation alters the developmental competence of bovine COCs. Therefore, for the first time, we demonstrate that application of TUDCA during IVM plays a crucial role in reducing ER stress and improves the meiotic maturation, oocyte quality, and subsequent embryonic development invitro.

scholarly journals 3β-Hydroxysteroid-Δ24 Reductase (DHCR24) Protects Pancreatic β Cells from Endoplasmic Reticulum Stress-Induced Apoptosis by Scavenging Excessive Intracellular Reactive Oxygen Species

2020 ◽  
Vol 2020 ◽  
pp. 1-11
Author(s):  
Yang Li ◽  
Xude Wang ◽  
Baoyu Yang ◽  
Haozhen Wang ◽  
Zhenzhong Ma ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Endoplasmic Reticulum ◽  
Er Stress ◽  
Reactive Oxygen ◽  
Intracellular Reactive Oxygen Species ◽  
Control Group ◽  
Oxygen Species ◽  
Protein Levels ◽  
Cell Dysfunction ◽  
Induced Apoptosis

There is accumulating evidence showing that apoptosis induced by endoplasmic reticulum (ER) stress plays a key role in pancreatic β cell dysfunction and insulin resistance. 3β-Hydroxysteroid-Δ24 Reductase (DHCR24) is a multifunctional enzyme located in the endoplasmic reticulum (ER), which has been previously shown to protect neuronal cells from ER stress-induced apoptosis. However, the role of DHCR24 in type 2 diabetes is only incompletely understood so far. In the present study, we induced ER stress by tunicamycin (TM) treatment and showed that infection of MIN6 cells with Ad-DHCR24-myc rendered these cells resistant to caspase-3-mediated apoptosis induced by TM, while cells transfected with siRNAs targeting DHCR24 were more sensitive to TM. Western blot analysis showed that TM treatment induced upregulation of Bip protein levels in both cells infected with Ad-LacZ (the control group) and Ad-DHCR24-myc, indicating substantial ER stress. Cells infected with Ad-LacZ exhibited a rapid and strong activation of ATF6 and p38, peaking at 3 h after TM exposure. Conversely, cells infected with Ad-DHCR24-myc showed a higher and more sustained activation of ATF6 and Bip than control cells. DHCR24 overexpression also inhibited the generation of intracellular reactive oxygen species (ROS) induced by ER stress and protected cells from apoptosis caused by treatment with both cholesterol and hydrogen peroxide. In summary, these data demonstrate, for the first time, that DHCR24 protects pancreatic β cells from apoptosis induced by ER stress.

scholarly journals Reactive Oxygen Species (ROS) Regulates Different Types of Cell Death by Acting as a Rheostat

2021 ◽  
Vol 2021 ◽  
pp. 1-17
Author(s):  
Gloria E. Villalpando-Rodriguez ◽  
Spencer B. Gibson
Keyword(s):  
Reactive Oxygen Species ◽  
Cell Death ◽  
Cellular Signaling ◽  
Reactive Oxygen ◽  
Oxygen Species ◽  
Regulatory Pathways ◽  
Disease States ◽  
Different Types ◽  
Response To Stress ◽  
Cell Death Mechanisms

Reactive oxygen species (ROS) are essential for cellular signaling and response to stress. The level of ROS and the type of ROS determine the ability of cells to undergo cell death. Furthermore, dysregulation of the antioxidant pathways is associated with many diseases. It has become apparent that cell death can occur through different mechanisms leading to the classifications of different types of cell death such as apoptosis, ferroptosis, and necroptosis. ROS play essential roles in all forms of cell death, but it is only now coming into focus that ROS control and determine the type of cell death that occurs in any given cell. Indeed, ROS may act as a rheostat allowing different cell death mechanisms to be engaged and crosstalk with different cell death types. In this review, we will describe the ROS regulatory pathways and how they control different types of cell death under normal and disease states. We will also propose how ROS could provide a mechanism of crosstalk between cell death mechanisms and act as a rheostat determining the type of cell death.

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