Emerging roles of endoplasmic reticulum-resident selenoproteins in the regulation of cellular stress responses and the implications for metabolic disease

2018 ◽  
Vol 475 (6) ◽  
pp. 1037-1057 ◽  
Author(s):  
Alex B. Addinsall ◽  
Craig R. Wright ◽  
Sof Andrikopoulos ◽  
Chris van der Poel ◽  
Nicole Stupka
Keyword(s):  
Metabolic Disease ◽  
Endoplasmic Reticulum ◽  
Stress Responses ◽  
Cellular Stress ◽  
Metabolic Stress ◽  
Metabolic Dysfunction ◽  
Iodothyronine Deiodinase ◽  
Inflammatory Stress ◽  
Cellular Stress Responses

Chronic metabolic stress leads to cellular dysfunction, characterized by excessive reactive oxygen species, endoplasmic reticulum (ER) stress and inflammation, which has been implicated in the pathogenesis of obesity, type 2 diabetes and cardiovascular disease. The ER is gaining recognition as a key organelle in integrating cellular stress responses. ER homeostasis is tightly regulated by a complex antioxidant system, which includes the seven ER-resident selenoproteins — 15 kDa selenoprotein, type 2 iodothyronine deiodinase and selenoproteins S, N, K, M and T. Here, the findings from biochemical, cell-based and mouse studies investigating the function of ER-resident selenoproteins are reviewed. Human experimental and genetic studies are drawn upon to highlight the relevance of these selenoproteins to the pathogenesis of metabolic disease. ER-resident selenoproteins have discrete roles in the regulation of oxidative, ER and inflammatory stress responses, as well as intracellular calcium homeostasis. To date, only two of these ER-resident selenoproteins, selenoproteins S and N have been implicated in human disease. Nonetheless, the potential of all seven ER-resident selenoproteins to ameliorate metabolic dysfunction warrants further investigation.

scholarly journals Differential regulation of cellular stress responses by the endoplasmic reticulum-resident Selenoprotein S (Seps1) in proliferating myoblasts versus myotubes

2018 ◽  
Vol 6 (24) ◽  
pp. e13926 ◽  
Author(s):  
Alex B. Addinsall ◽  
Sheree D. Martin ◽  
Fiona Collier ◽  
Xavier A. Conlan ◽  
Victoria C. Foletta ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Stress Responses ◽  
Cellular Stress ◽  
Differential Regulation ◽  
Selenoprotein S ◽  
Cellular Stress Responses

scholarly journals Context-Dependent Roles of RNA Modifications in Stress Responses and Diseases

2021 ◽  
Vol 22 (4) ◽  
pp. 1949
Author(s):  
Emma Wilkinson ◽  
Yan-Hong Cui ◽  
Yu-Ying He
Keyword(s):  
Stress Responses ◽  
Cell Biology ◽  
Developmental Disorders ◽  
Metabolic Diseases ◽  
Cellular Stress ◽  
Metabolic Stress ◽  
Rna Modifications ◽  
Cellular Stress Responses ◽  
Response To Stress

RNA modifications are diverse post-transcriptional modifications that regulate RNA metabolism and gene expression. RNA modifications, and the writers, erasers, and readers that catalyze these modifications, serve as important signaling machineries in cellular stress responses and disease pathogenesis. In response to stress, RNA modifications are mobilized to activate or inhibit the signaling pathways that combat stresses, including oxidative stress, hypoxia, therapeutic stress, metabolic stress, heat shock, DNA damage, and ER stress. The role of RNA modifications in response to these cellular stressors is context- and cell-type-dependent. Due to their pervasive roles in cell biology, RNA modifications have been implicated in the pathogenesis of different diseases, including cancer, neurologic and developmental disorders and diseases, and metabolic diseases. In this review, we aim to summarize the roles of RNA modifications in molecular and cellular stress responses and diseases.

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 Targeting the Incretin/Glucagon System With Triagonists to Treat Diabetes

2018 ◽  
Vol 39 (5) ◽  
pp. 719-738 ◽  
Author(s):  
Megan E Capozzi ◽  
Richard D DiMarchi ◽  
Matthias H Tschöp ◽  
Brian Finan ◽  
Jonathan E Campbell
Keyword(s):  
Metabolic Disease ◽  
Type 2 Diabetes ◽  
Bariatric Surgery ◽  
Drug Class ◽  
Clinical Findings ◽  
Metabolic Dysfunction ◽  
Multiple Receptors ◽  
Insulinotropic Peptide ◽  
The Brain

Abstract Glucagonlike peptide 1 (GLP-1) receptor agonists have been efficacious for the treatment of type 2 diabetes due to their ability to reduce weight and attenuate hyperglycemia. However, the activity of glucagonlike peptide 1 receptor–directed strategies is submaximal, and the only potent, sustainable treatment of metabolic dysfunction is bariatric surgery, necessitating the development of unique therapeutics. GLP-1 is structurally related to glucagon and glucose-dependent insulinotropic peptide (GIP), allowing for the development of intermixed, unimolecular peptides with activity at each of their respective receptors. In this review, we discuss the range of tissue targets and added benefits afforded by the inclusion of each of GIP and glucagon. We discuss considerations for the development of sequence-intermixed dual agonists and triagonists, highlighting the importance of evaluating balanced signaling at the targeted receptors. Several multireceptor agonist peptides have been developed and evaluated, and the key preclinical and clinical findings are reviewed in detail. The biological activity of these multireceptor agonists are founded in the success of GLP-1-directed strategies; by including GIP and glucagon components, these multireceptor agonists are thought to enhance GLP-1’s activities by broadening the tissue targets and synergizing at tissues that express multiple receptors, such at the brain and pancreatic isletβ cells. The development and utility of balanced, unimolecular multireceptor agonists provide both a useful tool for querying the actions of incretins and glucagon during metabolic disease and a unique drug class to treat type 2 diabetes with unprecedented efficacy.

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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