scholarly journals Sophorolipid exhibits antifungal activity by ROS mediated endoplasmic reticulum stress and mitochondrial dysfunction pathways in Candida albicans

RSC Advances ◽  
2019 ◽  
Vol 9 (71) ◽  
pp. 41639-41648 ◽  
Author(s):  
Farazul Haque ◽  
Nitish Kumar Verma ◽  
Mohammad Alfatah ◽  
Swati Bijlani ◽  
Mani Shankar Bhattacharyya
Keyword(s):  
Endoplasmic Reticulum ◽  
Cell Death ◽  
Candida Albicans ◽  
Antifungal Activity ◽  
Endoplasmic Reticulum Stress ◽  
Er Stress ◽  
Mitochondrial Dysfunction ◽  
Ros Generation

Sophorolipid induces ROS generation in C. albicans leading to mitochondrial dysfunction and ER stress followed by the release of Ca2+ ions (from the ER lumen) that enter mitochondria and further magnify ROS generation leading to cell death.

scholarly journals Ca2+ overload- and ROS-associated mitochondrial dysfunction contributes to δ-tocotrienol-mediated paraptosis in melanoma cells

APOPTOSIS ◽  
2021 ◽  
Author(s):  
Michela Raimondi ◽  
Fabrizio Fontana ◽  
Monica Marzagalli ◽  
Matteo Audano ◽  
Giangiacomo Beretta ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Cell Death ◽  
Mitochondrial Dysfunction ◽  
Atp Synthesis ◽  
Melanoma Cells ◽  
Human Melanoma ◽  
Ros Generation ◽  
Therapy Outcomes ◽  
Human Melanoma Cells ◽  
Oxphos Complex

Abstract Melanoma is an aggressive tumor with still poor therapy outcomes. δ-tocotrienol (δ-TT) is a vitamin E derivative displaying potent anti-cancer properties. Previously, we demonstrated that δ-TT triggers apoptosis in human melanoma cells. Here, we investigated whether it might also activate paraptosis, a non-canonical programmed cell death. In accordance with the main paraptotic features, δ-TT was shown to promote cytoplasmic vacuolization, associated with endoplasmic reticulum/mitochondrial dilation and protein synthesis, as well as MAPK activation in A375 and BLM cell lines. Moreover, treated cells exhibited a significant reduced expression of OXPHOS complex I and a marked decrease in oxygen consumption and mitochondrial membrane potential, culminating in decreased ATP synthesis and AMPK phosphorylation. This mitochondrial dysfunction resulted in ROS overproduction, found to be responsible for paraptosis induction. Additionally, δ-TT caused Ca2+ homeostasis disruption, with endoplasmic reticulum-derived ions accumulating in mitochondria and activating the paraptotic signaling. Interestingly, by using both IP3R and VDAC inhibitors, a close cause-effect relationship between mitochondrial Ca2+ overload and ROS generation was evidenced. Collectively, these results provide novel insights into δ-TT anti-melanoma activity, highlighting its ability to induce mitochondrial dysfunction-mediated paraptosis. Graphic Abstract δ-tocotrienol induces paraptotic cell death in human melanoma cells, causing endoplasmic reticulum dilation and mitochondrial swelling. These alterations induce an impairment of mitochondrial function, ROS production and calcium overload.

scholarly journals Induction of Paraptotic Cell Death in Breast Cancer Cells by a Novel Pyrazolo[3,4-h]quinoline Derivative through ROS Production and Endoplasmic Reticulum Stress

Antioxidants ◽  
2022 ◽  
Vol 11 (1) ◽  
pp. 117
Author(s):  
Phuong Linh Nguyen ◽  
Chang Hoon Lee ◽  
Heesoon Lee ◽  
Jungsook Cho
Keyword(s):  
Breast Cancer ◽  
Endoplasmic Reticulum ◽  
Cell Death ◽  
Er Stress ◽  
Molecular Mechanisms ◽  
Quinoline Derivative ◽  
Ros Generation ◽  
Protein Accumulation ◽  
Potential Candidate ◽  
Development Of Resistance

Chemotherapy has been a standard intervention for a variety of cancers to impede tumor growth, mainly by inducing apoptosis. However, development of resistance to this regimen has led to a growing interest and demand for drugs targeting alternative cell death modes, such as paraptosis. Here, we designed and synthesized a novel derivative of a pyrazolo[3,4-h]quinoline scaffold (YRL1091), evaluated its cytotoxic effect, and elucidated the underlying molecular mechanisms of cell death in MDA-MB-231 and MCF-7 breast cancer (BC) cells. We found that YRL1091 induced cytotoxicity in these cells with numerous cytoplasmic vacuoles, one of the distinct characteristics of paraptosis. YRL1091-treated BC cells displayed several other distinguishing features of paraptosis, excluding autophagy or apoptosis. Briefly, YRL1091-induced cell death was associated with upregulation of microtubule-associated protein 1 light chain 3B, downregulation of multifunctional adapter protein Alix, and activation of extracellular signal-regulated kinase 1/2 and c-Jun N-terminal kinase. Furthermore, the production of reactive oxygen species (ROS) and newly synthesized proteins were also observed, subsequently causing ubiquitinated protein accumulation and endoplasmic reticulum (ER) stress. Collectively, these results indicate that YRL1091 induces paraptosis in BC cells through ROS generation and ER stress. Therefore, YRL1091 can serve as a potential candidate for the development of a novel anticancer drug triggering paraptosis, which may provide benefit for the treatment of cancers resistant to conventional chemotherapy.

Pyridoxine Preferentially Induces Auditory Neuropathy Through Mitochondrial Dysfunction and Endoplasmic Reticulum Stress-Mediated Apoptosis

2019 ◽  
Vol 128 (6_suppl) ◽  
pp. 117S-124S ◽  
Author(s):  
Channy Park ◽  
Hyewon Lim ◽  
Sung K. Moon ◽  
Raekil Park
Keyword(s):  
Endoplasmic Reticulum ◽  
Cell Death ◽  
Protein Expression ◽  
Er Stress ◽  
Nerve Fiber ◽  
Apoptotic Cell ◽  
Auditory Neuropathy ◽  
Parp Cleavage ◽  
Ros Generation ◽  
Ganglion Neurons

Objectives: Auditory neuropathy due to toxicity mechanism of pyridoxine has not yet been fully documented. Therefore, the present study explored a direct mechanism underlying the effects of pyridoxine on auditory neuropathy in organ of Corti (OC) explants ex vivo and cochlear neuroblast cell line, VOT-33 in vitro. Methods: Primary OC explants containing spiral ganglion neurons and cultured VOT-33 cells were treated with pyridoxine. Results: In nerve fiber of primary OC explants, pyridoxine decreased staining for NF200, a neuro-cytoskeletal protein. We also found that pyridoxine-induced VOT-33 apoptosis, as indicated by accumulation of the sub-G0/G1 fraction, caspase-3 activation, and PARP cleavage. In addition, pyridoxine induced reactive oxygen species (ROS) generation and alteration of mitochondrial membrane potential transition (MPT), including Bcl-2 family protein expression and consequently Ca2+ accumulation and changes of endoplasmic reticulum (ER) stress-related protein expression such as phospho-PERK, caspase-12, Grp78, and CHOP. Conclusion: Pyridoxine preferentially induced severe cell death on nerve fiber in primary OC explants and markedly increased apoptotic cell death via mitochondria-mediated ER stress in VOT-33 cells.

Curcumin induces cell death of human papillary thyroid carcinoma BCPAP cells through endoplasmic reticulum stress

RSC Advances ◽  
2016 ◽  
Vol 6 (58) ◽  
pp. 52905-52912 ◽  
Author(s):  
Lixi Zhang ◽  
Li Zhang ◽  
Xian Cheng ◽  
Yanyan Gao ◽  
Jiandong Bao ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Cell Death ◽  
Papillary Thyroid Carcinoma ◽  
Endoplasmic Reticulum Stress ◽  
Thyroid Carcinoma ◽  
Er Stress ◽  
Signaling Pathway ◽  
Papillary Thyroid

Curcumin induced cell death of BCPAP cells via ER stress with activation of the ATF6/XBP-1 signaling pathway and Ca2+ release.

scholarly journals Protective Mechanisms of the Mitochondrial-Derived Peptide Humanin in Oxidative and Endoplasmic Reticulum Stress in RPE Cells

2017 ◽  
Vol 2017 ◽  
pp. 1-11 ◽  
Author(s):  
Leonid Minasyan ◽  
Parameswaran G. Sreekumar ◽  
David R. Hinton ◽  
Ram Kannan
Keyword(s):  
Oxidative Stress ◽  
Endoplasmic Reticulum ◽  
Cell Death ◽  
Er Stress ◽  
Apoptotic Cell ◽  
Retinal Pigment ◽  
Age Related Macular Degeneration ◽  
Ros Generation ◽  
Rpe Cells ◽  
Age Related

Age-related macular degeneration (AMD) is the leading cause of severe and irreversible vision loss and is characterized by progressive degeneration of the retina resulting in loss of central vision. The retinal pigment epithelium (RPE) is a critical site of pathology of AMD. Mitochondria and the endoplasmic reticulum which lie in close anatomic proximity to each other are targets of oxidative stress and endoplasmic reticulum (ER) stress, respectively, and contribute to the progression of AMD. The two organelles exhibit close interactive function via various signaling mechanisms. Evidence for ER-mitochondrial crosstalk in RPE under ER stress and signaling pathways of apoptotic cell death is presented. The role of humanin (HN), a prominent member of a newly discovered family of mitochondrial-derived peptides (MDPs) expressed from an open reading frame of mitochondrial 16S rRNA, in modulation of ER and oxidative stress in RPE is discussed. HN protected RPE cells from oxidative and ER stress-induced cell death by upregulation of mitochondrial GSH, inhibition of ROS generation, and caspase 3 and 4 activation. The underlying mechanisms of ER-mitochondrial crosstalk and modulation by exogenous HN are discussed. The therapeutic use of HN and related MDPs could potentially prove to be a valuable approach for treatment of AMD.

scholarly journals The Natural Occurring Compounds Targeting Endoplasmic Reticulum Stress

2016 ◽  
Vol 2016 ◽  
pp. 1-13 ◽  
Author(s):  
Hai Liu ◽  
Jianqiong Yang ◽  
Linfu Li ◽  
Weimei Shi ◽  
Xiaoliang Yuan ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Cell Death ◽  
Endoplasmic Reticulum Stress ◽  
Er Stress ◽  
Clinical Applications ◽  
Inflammatory Factors ◽  
Ros Production ◽  
Pharmacological Mechanism ◽  
Medical Benefits ◽  
Novel Strategy

ER stress has been implicated in pathophysiological development of many diseases. Persistent overwhelming stimuli trigger ER stress to initiate apoptosis, autophagy, and cell death. IRE1-JNK and eIF2α-CHOP signaling pathways are the two important players of ER stress, which is also modulated by ROS production, calcium disturbance, and inflammatory factors. ER stress has been developed as a novel strategy for diseases management. Recently, a vast of research focuses on the natural occurring compounds targeting ER stress, which results in medical benefits to human diseases. These small reported molecules mainly include polyphenols, alkaloids, and saponins. Many of them have been developed for use in clinical applications. To better understand the pharmacological mechanism of these molecules in ER stress in diseases, efforts have been made to discover and deliver medical merits. In this paper, we will summarize the natural occurring compounds targeting ER stress.

scholarly journals Eukarion-134 Attenuates Endoplasmic Reticulum Stress-Induced Mitochondrial Dysfunction in Human Skeletal Muscle Cells

Antioxidants ◽  
2020 ◽  
Vol 9 (8) ◽  
pp. 710
Author(s):  
Anastasia Thoma ◽  
Max Lyon ◽  
Nasser Al-Shanti ◽  
Gareth A. Nye ◽  
Robert G. Cooper ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Endoplasmic Reticulum ◽  
Er Stress ◽  
Mitochondrial Dysfunction ◽  
Muscle Weakness ◽  
Ros Generation ◽  
Transcriptional Level ◽  
Mrna Levels ◽  
Human Skeletal Muscle Cells ◽  
The Impact

Maladaptive endoplasmic reticulum (ER) stress is associated with modified reactive oxygen species (ROS) generation and mitochondrial abnormalities; and is postulated as a potential mechanism involved in muscle weakness in myositis, an acquired autoimmune neuromuscular disease. This study investigates the impact of ROS generation in an in vitro model of ER stress in skeletal muscle, using the ER stress inducer tunicamycin (24 h) in the presence or absence of a superoxide dismutase/catalase mimetic Eukarion (EUK)-134. Tunicamycin induced maladaptive ER stress, which was mitigated by EUK-134 at the transcriptional level. ER stress promoted mitochondrial dysfunction, described by substantial loss of mitochondrial membrane potential, as well as a reduction in respiratory control ratio, reserve capacity, phosphorylating respiration, and coupling efficiency, which was ameliorated by EUK-134. Tunicamycin induced ROS-mediated biogenesis and fusion of mitochondria, which, however, had high propensity of fragmentation, accompanied by upregulated mRNA levels of fission-related markers. Increased cellular ROS generation was observed under ER stress that was prevented by EUK-134, even though no changes in mitochondrial superoxide were noticeable. These findings suggest that targeting ROS generation using EUK-134 can amend aspects of ER stress-induced changes in mitochondrial dynamics and function, and therefore, in instances of chronic ER stress, such as in myositis, quenching ROS generation may be a promising therapy for muscle weakness and dysfunction.

scholarly journals Hyperglycemia Induces Endoplasmic Reticulum Stress in Atrial Cardiomyocytes, and Mitofusin-2 Downregulation Prevents Mitochondrial Dysfunction and Subsequent Cell Death

2020 ◽  
Vol 2020 ◽  
pp. 1-14
Author(s):  
Ming Yuan ◽  
Mengqi Gong ◽  
Zhiwei Zhang ◽  
Lei Meng ◽  
Gary Tse ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Endoplasmic Reticulum ◽  
Cell Death ◽  
Er Stress ◽  
Mitochondrial Dysfunction ◽  
High Glucose ◽  
Atrial Remodeling ◽  
Mitofusin 2 ◽  
Mitochondrial Oxidative Stress ◽  
Atrial Cardiomyocytes

Mitochondrial oxidative stress and dysfunction play an important role of atrial remodeling and atrial fibrillation (AF) in diabetes mellitus. Endoplasmic reticulum (ER) stress has been linked to both physiological and pathological states including diabetes. The aim of this project is to explore the roles of ER stress in hyperglycemia-induced mitochondrial dysfunction and cell death of atrial cardiomyocytes. High glucose upregulated ER stress, mitochondrial oxidative stress, and mitochondria-associated ER membrane (MAM)- enriched proteins (such as glucose-regulated protein 75 (GRP75) and mitofusin-2 (Mfn2)) of primary cardiomyocytes in vitro. Sodium phenylbutyrate (4-PBA) prevented the above changes. Silencing of Mfn2 in HL-1 cells decreased the Ca2+ transfer from ER to mitochondria under ER stress conditions, which were induced by the ER stress agonist, tunicamycin (TM). Electron microscopy data suggested that Mfn2 siRNA significantly disrupted ER-mitochondria tethering in ER stress-injured HL-1 cells. Mfn2 silencing attenuated mitochondrial oxidative stress and Ca2+ overload, increased mitochondrial membrane potential and mitochondrial oxygen consumption, and protected cells from TM-induced apoptosis. In summary, Mfn2 plays an important role in high glucose-induced ER stress in atrial cardiomyocytes, and Mfn2 silencing prevents mitochondrial Ca2+ overload-mediated mitochondrial dysfunction, thereby decreasing ER stress-mediated cardiomyocyte cell death.

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