scholarly journals The alkyl side chain of PACA nanoparticles dictates the impact on cellular stress responses and the mode of particle-induced cell death

2018 ◽  
Author(s):  
Marzena Szwed ◽  
Tonje Sønstevold ◽  
Anders Øverbye ◽  
Nikolai Engedal ◽  
Beata Grallert ◽  
...  
Keyword(s):  
Cell Death ◽  
Stress Responses ◽  
Cellular Response ◽  
Cellular Stress ◽  
Cell Interaction ◽  
Multidrug Resistant ◽  
Detailed Knowledge ◽  
Promising Alternative ◽  
Cellular Stress Responses ◽  
The Impact

AbstractFor optimal exploitation of nanoparticles (NPs) in biomedicine, and to predict nanotoxicity, detailed knowledge on the cellular responses to cell-bound or internalized NPs is imperative. The outcome of NP-cell interaction is dictated by the type and magnitude of the NP insult and the cellular response. Here, we have systematically studied the impact of minor differences in NP composition on cellular stress responses and viability by using highly similar poly(alkylcyanoacrylate) (PACA) particles. Surprisingly, PACA particles differing only in their alkyl side chains; butyl (PBCA), ethylbutyl (PEBCA), or octyl (POCA), respectively, induced different stress responses and modes of cell death in human cell lines. POCA particles induced endoplasmic reticulum stress and apoptosis. In contrast, PBCA and PEBCA particles induced lipid peroxidation by depletion of the main cellular antioxidant glutathione (GSH), in a manner depending on the levels of the GSH precursor cystine, and transcription of the cystine transporter SLC7A11 regulated by ATF4 and Nrf2. Intriguingly, these particles activated the recently discovered cell death mechanism ferroptosis, which constitutes a promising alternative for targeting multidrug-resistant cancer stem-like cells. Of the two, PBCA was the strongest inducer. In summary, our findings highlight the cellular sensitivity to nanoparticle composition and have important implications for the choice of PACA monomer in therapeutical settings.

scholarly journals Effect of Combined Stressors on C. elegans Lifespan

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. 667-667
Author(s):  
Bradford Hull ◽  
George Sutphin
Keyword(s):  
Heavy Metal ◽  
Stress Response ◽  
Stress Responses ◽  
Cellular Response ◽  
Multiple Stressors ◽  
Cellular Stress ◽  
Cellular Stress Response ◽  
C Elegans ◽  
Arsenic Copper ◽  
The Impact

Abstract Cellular stress is a fundamental component of age-associated disease. Cells experience many forms of stress (oxidative, heavy metal, etc.), and as we age the burden of stress and resulting damage increases while our cells’ ability to deal with the consequences becomes diminished due to dysregulation of cellular stress response pathways. By understanding how cells respond to stress we aim to slow age-associated deterioration and develop treatment targets for age-associated disease. The majority of past work has focused on understanding responses to individual stressors. In contrast, how pathology and stress responses differ in the presence of multiple stressors is relatively unknown; we investigate that here. We cultured worms on agar plates with different combinations of arsenic, copper, and DTT (which create oxidative/proteotoxic, heavy metal, and endoplasmic reticulum (ER) stress, respectively) at doses that result in 20% lifespan reduction individually and measured the effect on lifespan. We found that arsenic/copper and arsenic/DTT combinations created additive lifespan reductions while the copper/DTT combination created an antagonistic lifespan reduction when compared to controls (p<0.05). This antagonistic toxicity suggests an interaction either between the mechanisms of toxicity or the cellular response to copper and DTT. We are now evaluating the impact of copper and DTT individually and in combination on unfolded protein and heavy metal response pathways to understand the underlying mechanism of the interaction. Additionally, we are continuing to screen stressors to identify combinations that cause non-additive (synergistic or antagonistic) toxicity to build a comprehensive model of the genetic stress response network in C. elegans.

scholarly journals Cellular Stress Responses: Cell Survival and Cell Death

2010 ◽  
Vol 2010 ◽  
pp. 1-23 ◽  
Author(s):  
Simone Fulda ◽  
Adrienne M. Gorman ◽  
Osamu Hori ◽  
Afshin Samali
Keyword(s):  
Cell Death ◽  
Stress Responses ◽  
Cellular Stress ◽  
World Health ◽  
Health Issues ◽  
Survival Pathways ◽  
Cellular Stress Responses ◽  
A Cell ◽  
Exogenous Factors ◽  
Stressed Cell

Cells can respond to stress in various ways ranging from the activation of survival pathways to the initiation of cell death that eventually eliminates damaged cells. Whether cells mount a protective or destructive stress response depends to a large extent on the nature and duration of the stress as well as the cell type. Also, there is often the interplay between these responses that ultimately determines the fate of the stressed cell. The mechanism by which a cell dies (i.e., apoptosis, necrosis, pyroptosis, or autophagic cell death) depends on various exogenous factors as well as the cell's ability to handle the stress to which it is exposed. The implications of cellular stress responses to human physiology and diseases are manifold and will be discussed in this review in the context of some major world health issues such as diabetes, Parkinson's disease, myocardial infarction, and cancer.

scholarly journals Small variations in nanoparticle structure dictate differential cellular stress responses and mode of cell death

2019 ◽  
Vol 13 (6) ◽  
pp. 761-782 ◽  
Author(s):  
Marzena Szwed ◽  
Tonje Sønstevold ◽  
Anders Øverbye ◽  
Nikolai Engedal ◽  
Beata Grallert ◽  
...  
Keyword(s):  
Cell Death ◽  
Stress Responses ◽  
Cellular Stress ◽  
Cellular Stress Responses ◽  
Nanoparticle Structure

scholarly journals Flavonoids: Potential Candidates for the Treatment of Neurodegenerative Disorders

Biomedicines ◽  
2021 ◽  
Vol 9 (2) ◽  
pp. 99
Author(s):  
Shweta Devi ◽  
Vijay Kumar ◽  
Sandeep Kumar Singh ◽  
Ashish Kant Dubey ◽  
Jong-Joo Kim
Keyword(s):  
Stress Response ◽  
Stress Responses ◽  
Neurodegenerative Disorders ◽  
Cell Damage ◽  
Cellular Stress ◽  
Clinical Manifestations ◽  
Cellular Stress Response ◽  
Dramatic Rise ◽  
Cellular Stress Responses

Neurodegenerative disorders, such as Parkinson’s disease (PD), Alzheimer’s disease (AD), Amyotrophic lateral sclerosis (ALS), and Huntington’s disease (HD), are the most concerning disorders due to the lack of effective therapy and dramatic rise in affected cases. Although these disorders have diverse clinical manifestations, they all share a common cellular stress response. These cellular stress responses including neuroinflammation, oxidative stress, proteotoxicity, and endoplasmic reticulum (ER)-stress, which combats with stress conditions. Environmental stress/toxicity weakened the cellular stress response which results in cell damage. Small molecules, such as flavonoids, could reduce cellular stress and have gained much attention in recent years. Evidence has shown the potential use of flavonoids in several ways, such as antioxidants, anti-inflammatory, and anti-apoptotic, yet their mechanism is still elusive. This review provides an insight into the potential role of flavonoids against cellular stress response that prevent the pathogenesis of neurodegenerative disorders.

scholarly journals CRISPR-Mediated Endogenous Activation of Fibroin Heavy Chain Gene Triggers Cellular Stress Responses in Bombyx mori Embryonic Cells

Insects ◽  
2021 ◽  
Vol 12 (6) ◽  
pp. 552
Author(s):  
Wenbo Hu ◽  
Xiaogang Wang ◽  
Sanyuan Ma ◽  
Zhangchuan Peng ◽  
Yang Cao ◽  
...  
Keyword(s):  
Bombyx Mori ◽  
Heavy Chain ◽  
Stress Responses ◽  
Cellular Stress ◽  
Silk Gland ◽  
Cellular Stress Response ◽  
Molar Ratio ◽  
Chain Gene ◽  
Gland Cells ◽  
Cellular Stress Responses

The silkworm Bombyx mori is an economically important insect, as it is the main producer of silk. Fibroin heavy chain (FibH) gene, encoding the core component of silk protein, is specifically and highly expressed in silk gland cells but not in the other cells. Although the silkworm FibH gene has been well studied in transcriptional regulation, its biological functions in the development of silk gland cells remain elusive. In this study, we constructed a CRISPRa system to activate the endogenous transcription of FibH in Bombyx mori embryonic (BmE) cells, and the mRNA expression of FibH was successfully activated. In addition, we found that FibH expression was increased to a maximum at 60 h after transient transfection of sgRNA/dCas9-VPR at a molar ratio of 9:1. The qRT-PCR analysis showed that the expression levels of cellular stress response-related genes were significantly up-regulated along with activated FibH gene. Moreover, the lyso-tracker red and monodansylcadaverine (MDC) staining assays revealed an apparent appearance of autophagy in FibH-activated BmE cells. Therefore, we conclude that the activation of FibH gene leads to up-regulation of cellular stress responses-related genes in BmE cells, which is essential for understanding silk gland development and the fibroin secretion process in B. mori.

scholarly journals Cellular Stress Responses: A Balancing Act

2010 ◽  
Vol 40 (2) ◽  
pp. 175 ◽  
Author(s):  
Feng Chen ◽  
Allyson Evans ◽  
John Pham ◽  
Brian Plosky
Keyword(s):  
Stress Responses ◽  
Cellular Stress ◽  
Cellular Stress Responses

scholarly journals The Phosphorylation-Dependent Regulation of Mitochondrial Proteins in Stress Responses

2012 ◽  
Vol 2012 ◽  
pp. 1-12 ◽  
Author(s):  
Yusuke Kanamaru ◽  
Shiori Sekine ◽  
Hidenori Ichijo ◽  
Kohsuke Takeda
Keyword(s):  
Stress Responses ◽  
Map Kinases ◽  
Mitochondrial Fission ◽  
Cellular Stress ◽  
Degradation Process ◽  
Mitochondrial Proteins ◽  
Phosphoglycerate Mutase ◽  
Mitogen Activated Protein ◽  
Cellular Stress Responses ◽  
Autophagic Degradation

To maintain cellular homeostasis, cells are equipped with precise systems that trigger the appropriate stress responses. Mitochondria not only provide cellular energy but also integrate stress response signaling pathways, including those regulating cell death. Several lines of evidence suggest that the mitochondrial proteins that function in this process, such as Bcl-2 family proteins in apoptosis and phosphoglycerate mutase family member 5 (PGAM5) in necroptosis, are regulated by several kinases. It has also been suggested that the phosphorylation-dependent regulation of mitochondrial fission machinery, dynamin-related protein 1 (Drp1), facilitates appropriate cellular stress responses. However, mitochondria themselves are also damaged by various stresses. To avoid the deleterious effects exerted by damaged mitochondria, cells remove these mitochondria in a selective autophagic degradation process called mitophagy. Interestingly, several kinases, such as PTEN-induced putative kinase 1 (PINK1) in mammals and stress-responsive mitogen-activated protein (MAP) kinases in yeast, have recently been shown to be involved in mitophagy. In this paper, we focus on the phosphorylation-dependent regulation of mitochondrial proteins and discuss the roles of this regulation in the mitochondrial and cellular stress responses.

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