A pattern of cell death induced by 40 kHz ultrasound in yeast cell model

Dendropanax morbifera leaves (DML) have long been used as traditional medicine to treat diverse symptoms in Korea. Ethyl acetate-soluble extracts of DML (DMLE) rescued HT22 mouse hippocampal neuronal cells from glutamate (Glu)-induced oxidative cell death; however, the protective compounds and mechanisms remain unknown. Here, we aimed to identify the neuroprotective ingredients and mechanisms of DMLE in the Glu-HT22 cell model. Five antioxidant compounds were isolated from DMLE and characterized as chlorogenic acid, hyperoside, isoquercitrin, quercetin, and rutin by spectroscopic methods. Isoquercitrin and quercetin significantly inhibited Glu-induced oxidative cell death by restoring intracellular reactive oxygen species (ROS) levels and mitochondrial superoxide generation, Ca2+ dysregulation, mitochondrial dysfunction, and nuclear translocation of apoptosis-inducing factor. These two compounds significantly increased the expression levels of nuclear factor erythroid-2-related factor 2 (Nrf2) and heme oxygenase 1 (HO-1) in the presence or absence of Glu treatment. Combinatorial treatment of the five compounds based on the equivalent concentrations in DMLE showed that significant protection was found only in the cells cotreated with isoquercitrin and quercetin, both of whom showed prominent synergism, as assessed by drug–drug interaction analysis. These findings suggest that isoquercitrin and quercetin are the active principles representing the protective effects of DMLE, and these effects were mediated by the Nrf2/HO-1 pathway.

Download Full-text

2-Methoxyestradiol and Its Combination with a Natural Compound, Ferulic Acid, Induces Melanoma Cell Death via Downregulation of Hsp60 and Hsp90

Journal of Oncology ◽

10.1155/2019/9293416 ◽

2019 ◽

Vol 2019 ◽

pp. 1-12 ◽

Cited By ~ 1

Author(s):

Anna Kamm ◽

Paulina Przychodzeń ◽

Alicja Kuban–Jankowska ◽

Antonella Marino Gammazza ◽

Francesco Cappello ◽

...

Keyword(s):

Cell Death ◽

Ferulic Acid ◽

Melanoma Cell ◽

Cell Model ◽

Clinical Importance ◽

Hsp70 Expression ◽

Cellular Model ◽

Anticancer Efficacy ◽

Cancer Cell Death ◽

A375 Melanoma

Melanoma is an aggressive type of skin cancer with one of the highest mortality rates. Notably, its incidence in the last few decades has increased faster than any other cancer. Therefore, searching for novel anticancer therapies is of great clinical importance. In the present study, we investigated the anticancer potential of 2-methoxyestradiol, potent chemotherapeutic, in the A375 melanoma cellular model. In order to furthermore evaluate the anticancer efficacy of 2-methoxyestradiol, we have additionally combined the treatment with a naturally occurring polyphenol, ferulic acid. The results were obtained using the melanoma A375 cellular model. In the study, we used MTT assay, flow cytometry, and western blot techniques. Herein, we have evidenced that the molecular mechanism of action of 2-methoxyestradiol and ferulic acid is partly related to the reduction of Hsp60 and Hsp90 levels and the induction of nitric oxide in the A375 melanoma cell model, while no changes were observed in Hsp70 expression after 2-methoxyestradiol and ferulic acid treatment separately or in combination. This is especially important in case of chemoresistance mechanisms because the accumulation of Hsp70 reduces induction of cancer cell death, thus decreasing antitumour efficacy.

Download Full-text

Gene-dependent yeast cell death pathway requires AP-3 vesicle trafficking leading to vacuole membrane permeabilization

10.1101/2021.08.02.454728 ◽

2021 ◽

Author(s):

Zachary D Stolp ◽

Madhura Kulkarni ◽

Yining Liu ◽

Chengzhang Zhu ◽

Alizay Jalisi ◽

...

Keyword(s):

Cell Death ◽

Yeast Cell ◽

Vesicle Trafficking ◽

Membrane Integrity ◽

Time Lapse ◽

Membrane Permeabilization ◽

Cell Death Pathway ◽

Sequence Of Events ◽

A Genome ◽

Lysosome Membrane

Unicellular eukaryotes are suggested to undergo self-inflicted destruction. However, molecular details are sparse by comparison to the mechanisms of cell death known for human cells and animal models. Here we report a molecular pathway in Saccharomyces cerevisiae leading to vacuole/lysosome membrane permeabilization and cell death. Following exposure to heat-ramp conditions, a model of environmental stress, we observed that yeast cell death occurs over several hours, suggesting an ongoing molecular dying process. A genome-wide screen for death-promoting factors identified all subunits of the AP-3 adaptor complex. AP-3 promotes stress-induced cell death through its Arf1-GTPase-dependent vesicle trafficking function, which is required to transport and install proteins on the vacuole/lysosome membrane, including a death-promoting protein kinase Yck3. Time-lapse microscopy revealed a sequence of events where AP-3-dependent vacuole permeability occurs hours before the loss of plasma membrane integrity. An AP-3-dependent cell death pathway appears to be conserved in the human pathogen Cryptococcus neoformans.

Download Full-text

Intracellular amyloid toxicity induces oxytosis/ferroptosis regulated cell death

Cell Death and Disease ◽

10.1038/s41419-020-03020-9 ◽

2020 ◽

Vol 11 (10) ◽

Cited By ~ 2

Author(s):

Ling Huang ◽

Daniel B. McClatchy ◽

Pamela Maher ◽

Zhibin Liang ◽

Jolene K. Diedrich ◽

...

Keyword(s):

Cell Death ◽

Cell Model ◽

Early Stage ◽

Metabolic Reprogramming ◽

Therapeutic Interventions ◽

Amyloid Toxicity ◽

Cell Death Pathway ◽

Regulated Cell Death ◽

Metabolomic Data ◽

Basic Biology

Abstract Amyloid beta (Aβ) accumulates within neurons in the brains of early stage Alzheimer’s disease (AD) patients. However, the mechanism underlying its toxicity remains unclear. Here, a triple omics approach was used to integrate transcriptomic, proteomic, and metabolomic data collected from a nerve cell model of the toxic intracellular aggregation of Aβ. It was found that intracellular Aβ induces profound changes in the omics landscape of nerve cells that are associated with a pro-inflammatory, metabolic reprogramming that predisposes cells to die via the oxytosis/ferroptosis regulated cell death pathway. Notably, the degenerative process included substantial alterations in glucose metabolism and mitochondrial bioenergetics. Our findings have implications for the understanding of the basic biology of proteotoxicity, aging, and AD as well as for the development of future therapeutic interventions designed to target the oxytosis/ferroptosis regulated cell death pathway in the AD brain.

Download Full-text

Effects of Levosimendan on Inflammation and Oxidative Stress Pathways in a Lipopolysaccharide-Stimulated Human Endothelial Cell Model

Biological Research For Nursing ◽

10.1177/1099800419861694 ◽

2019 ◽

Vol 21 (5) ◽

pp. 466-472 ◽

Cited By ~ 1

Author(s):

Raquel Rodríguez-González ◽

Piero Pollesello ◽

Aurora Baluja ◽

Julián Álvarez

Keyword(s):

Oxidative Stress ◽

Cell Death ◽

Endothelial Cell ◽

Molecular Mechanisms ◽

Cell Model ◽

Acute Decompensated Heart Failure ◽

Umbilical Vein ◽

Organ Protection ◽

Endothelial Cell Death ◽

And Oxidative Stress

Levosimendan is a myocardial Ca2+sensitizer and opener of ATP-dependent potassium channels with inotropic, vasodilating, and cardioprotective properties. It was originally developed for the treatment of acute decompensated heart failure, but its complex mechanism of action means that it could also play a role in organ protection in response to infection. Using an in vitro approach, we explored whether levosimendan administration influenced cell responses to lipopolysaccharide (LPS). Primary human umbilical vein endothelial cells were stimulated with 1 µg/ml LPS from Escherichia coli ( E. coli). Cells were treated with levosimendan at 0, 0.1, 1, or 10 µM 3 hr later. Samples were taken 24 hr after treatment to measure cell necrosis, apoptosis, pro-inflammatory mediators (interleukin 6 [IL-6] and toll-like receptor 4 [TLR4]), and oxidative stress (total reactive oxygen species/reactive nitrogen species [ROS/RNS]). Levosimendan at 1 and 10 µM protected against LPS-induced endothelial cell death and reduced TLR4 expression ( p < .05). All doses reduced levels of IL-6 and ROS/RNS ( p < .05). Findings suggest that levosimendan may exert protective effects against endothelial cell death in this model via attenuation of inflammation and oxidative stress pathways. Future studies might explore the potential beneficial role of levosimendan in modulating molecular mechanisms triggered by infections.

Download Full-text