scholarly journals Proteome plasticity in response to persistent environmental change

2021 ◽  
Author(s):  
Matthew Domnauer ◽  
Fan Zheng ◽  
Liying Li ◽  
Yanxiao Zhang ◽  
Catherine E. Chang ◽  
...  
Keyword(s):  
Environmental Change ◽  
Temperature Change ◽  
Stress Responses ◽  
Variable Component ◽  
Temperature Sensitive ◽  
Cellular Functions ◽  
Alternative Conformation ◽  
Conformational Plasticity ◽  
Cellular Stress Responses

Temperature is a variable component of the environment and all organisms must deal with or adapt to temperature change. Acute temperature change activates cellular stress responses resulting in the refolding or removal of damaged proteins. However, how organisms adapt to long-term temperature change remains largely unexplored. Here, we report that budding yeast responds to long-term high temperature challenge by switching from chaperone induction to the reduction of temperature sensitive proteins and re-localizing a portion of its proteome. Surprisingly, we also find many proteins adopt an alternative conformation. Using Fet3p as an example, we find that the temperature-dependent conformational difference is accompanied by distinct thermostability, subcellular localization, and importantly, cellular functions. We postulate that in addition to the known mechanisms of adaptation, conformational plasticity allows some polypeptides to acquire new biophysical properties and functions when environmental change endures.

Dihydroceramides: Their emerging physiological roles and functions in cancer and metabolic diseases

2020 ◽  
Author(s):  
Floriane Lachkar ◽  
Pascal Ferre ◽  
Fabienne Foufelle ◽  
Alexandra Papaioannou
Keyword(s):  
Stress Responses ◽  
Metabolic Diseases ◽  
De Novo ◽  
Metabolic Intermediates ◽  
New Class ◽  
Survival Pathways ◽  
Long Time ◽  
Cellular Stress Responses

Dihydroceramides are a type of sphingolipids that for a long time were regarded as biologically inactive. They are metabolic intermediates of the de novo sphingolipid synthesis pathway, and are converted into ceramides with the addition of a double bond. Ceramides are abundant in tissues and have well-established biological functions. On the contrary, dihydroceramides are less prevalent and despite their hitherto characterization as inert lipids, studies of the last decade begun to unravel their implication in various biological processes distinct from those involving ceramides. These processes include cellular stress responses and autophagy, cell growth, pro-death or pro-survival pathways, hypoxia and immune responses. In addition, their plasma concentration has been related to metabolic diseases and shown as a long-term predictor of type 2 diabetes onset. They are thus important players and potential biomarkers in pathologies ranging from diabetes to cancer and neurodegenerative diseases. The purpose of this mini-review is to highlight the emergence of dihydroceramides as a new class of bioactive sphingolipids by reporting recent advances on their biological characterization and pathological implications, focusing on cancer and metabolic diseases.

scholarly journals The nuclear envelope and its involvement in cellular stress responses

2011 ◽  
Vol 39 (6) ◽  
pp. 1795-1798 ◽  
Author(s):  
Ashraf N. Malhas ◽  
David J. Vaux
Keyword(s):  
Transcription Factors ◽  
Nuclear Envelope ◽  
Stress Responses ◽  
Structural Integrity ◽  
Cellular Stress ◽  
Cellular Functions ◽  
Different Types ◽  
Cellular Stress Responses ◽  
Development And Differentiation ◽  
The Many

The nuclear envelope is not only important for the structural integrity of the nucleus, but also involved in a number of cellular functions. It has been shown to be important for maintaining and controlling chromatin organization, sequestering transcription factors, replication, transcription and signalling. The nuclear envelope is thus important for development and differentiation, and some of its components are essential for cell viability. Among the many functions which are emerging for the nuclear envelope is its involvement in protecting the cell against different types of cellular stress. In the present paper, we review key findings which describe the roles of nuclear envelope components in responses to common types of stress conditions.

scholarly journals SIRT7-dependent deacetylation of NPM promotes p53 stabilization following UV-induced genotoxic stress

2021 ◽  
Vol 118 (5) ◽  
pp. e2015339118
Author(s):  
Alessandro Ianni ◽  
Poonam Kumari ◽  
Shahriar Tarighi ◽  
Nicolas G. Simonet ◽  
Daniela Popescu ◽  
...  
Keyword(s):  
Uv Irradiation ◽  
Stress Responses ◽  
Decisive Role ◽  
Genotoxic Stress ◽  
Cellular Functions ◽  
Intrinsic Cues ◽  
Cellular Stress Responses ◽  
Stress Dependent

Adaptation to different forms of environmental stress is crucial for maintaining essential cellular functions and survival. The nucleolus plays a decisive role as a signaling hub for coordinating cellular responses to various extrinsic and intrinsic cues. p53 levels are normally kept low in unstressed cells, mainly due to E3 ubiquitin ligase MDM2-mediated degradation. Under stress, nucleophosmin (NPM) relocates from the nucleolus to the nucleoplasm and binds MDM2, thereby preventing degradation of p53 and allowing cell-cycle arrest and DNA repair. Here, we demonstrate that the mammalian sirtuin SIRT7 is an essential component for the regulation of p53 stability during stress responses induced by ultraviolet (UV) irradiation. The catalytic activity of SIRT7 is substantially increased upon UV irradiation through ataxia telangiectasia mutated and Rad3 related (ATR)-mediated phosphorylation, which promotes efficient deacetylation of the SIRT7 target NPM. Deacetylation is required for stress-dependent relocation of NPM into the nucleoplasm and MDM2 binding, thereby preventing ubiquitination and degradation of p53. In the absence of SIRT7, stress-dependent stabilization of p53 is abrogated, both in vitro and in vivo, impairing cellular stress responses. The study uncovers an essential SIRT7-dependent mechanism for stabilization of the tumor suppressor p53 in response to genotoxic stress.

scholarly journals A c-Myc–SIRT1 feedback loop regulates cell growth and transformation

2009 ◽  
Vol 185 (2) ◽  
pp. 203-211 ◽  
Author(s):  
Jian Yuan ◽  
Katherine Minter-Dykhouse ◽  
Zhenkun Lou
Keyword(s):  
Drosophila Melanogaster ◽  
Cell Growth ◽  
Life Span ◽  
Stress Responses ◽  
Feedback Loop ◽  
Cellular Transformation ◽  
Cellular Functions ◽  
Cellular Stress Responses ◽  
Protein Deacetylase

The protein deacetylase SIRT1 has been implicated in a variety of cellular functions, including development, cellular stress responses, and metabolism. Increasing evidence suggests that similar to its counterpart, Sir2, in yeast, Caenorhabditis elegans, and Drosophila melanogaster, SIRT1 may function to regulate life span in mammals. However, SIRT1's role in cancer is unclear. During our investigation of SIRT1, we found that c-Myc binds to the SIRT1 promoter and induces SIRT1 expression. However, SIRT1 interacts with and deacetylates c-Myc, resulting in decreased c-Myc stability. As a consequence, c-Myc's transformational capability is compromised in the presence of SIRT1. Overall, our experiments identify a c-Myc–SIRT1 feedback loop in the regulation of c-Myc activity and cellular transformation, supporting/suggesting a role of SIRT1 in tumor suppression.

scholarly journals Therapies for galactosemia: a patent landscape

2020 ◽  
Vol 9 (2) ◽  
pp. 45-51
Author(s):  
David J Timson
Keyword(s):  
Aldose Reductase ◽  
Stress Responses ◽  
Cellular Stress ◽  
Current Treatment ◽  
Novel Therapies ◽  
Aldose Reductase Inhibitors ◽  
Reductase Inhibitors ◽  
Patent Landscape ◽  
Cellular Stress Responses

Galactosemia is the inherited inability to metabolise galactose. The most common results from a lack of galactose 1-phosphate uridylyltransferase activity. The current treatment, removal of galactose from the diet, is inadequate and often fails to prevent long-term complications. Since 2015, three patents have been filed describing novel therapies. These are: the use of aldose reductase inhibitors to reduce cataracts and, possibly, other symptoms; salubrinal to stimulate cellular stress responses; mRNA therapy to increase cellular galactose 1-phosphate uridylyltransferase activity. The viability of all three is supported by academic studies. The potential and drawbacks of all three are discussed and evaluated.

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 Long-Term Exposure to Nanosized TiO2 Triggers Stress Responses and Cell Death Pathways in Pulmonary Epithelial Cells

2021 ◽  
Vol 22 (10) ◽  
pp. 5349
Author(s):  
Mayes Alswady-Hoff ◽  
Johanna Samulin Erdem ◽  
Santosh Phuyal ◽  
Oskar Knittelfelder ◽  
Animesh Sharma ◽  
...  
Keyword(s):  
Cell Death ◽  
Epithelial Cells ◽  
Health Effects ◽  
Stress Responses ◽  
Cell Stress ◽  
Lipid Classes ◽  
Long Term Effects ◽  
Cell Death Pathways ◽  
Pulmonary Epithelial Cells

There is little in vitro data available on long-term effects of TiO2 exposure. Such data are important for improving the understanding of underlying mechanisms of adverse health effects of TiO2. Here, we exposed pulmonary epithelial cells to two doses (0.96 and 1.92 µg/cm2) of TiO2 for 13 weeks and effects on cell cycle and cell death mechanisms, i.e., apoptosis and autophagy were determined after 4, 8 and 13 weeks of exposure. Changes in telomere length, cellular protein levels and lipid classes were also analyzed at 13 weeks of exposure. We observed that the TiO2 exposure increased the fraction of cells in G1-phase and reduced the fraction of cells in G2-phase, which was accompanied by an increase in the fraction of late apoptotic/necrotic cells. This corresponded with an induced expression of key apoptotic proteins i.e., BAD and BAX, and an accumulation of several lipid classes involved in cellular stress and apoptosis. These findings were further supported by quantitative proteome profiling data showing an increase in proteins involved in cell stress and genomic maintenance pathways following TiO2 exposure. Altogether, we suggest that cell stress response and cell death pathways may be important molecular events in long-term health effects of TiO2.

scholarly journals In-Frame and Frameshift Mutations in Zebrafish presenilin 2 Affect Different Cellular Functions in Young Adult Brains

2021 ◽  
pp. 1-10
Author(s):  
Karissa Barthelson ◽  
Stephen Martin Pederson ◽  
Morgan Newman ◽  
Haowei Jiang ◽  
Michael Lardelli
Keyword(s):  
Cell Cycle ◽  
Young Adult ◽  
Oxidative Phosphorylation ◽  
Frameshift Mutation ◽  
Long Term Potentiation ◽  
Cellular Functions ◽  
Reading Frame ◽  
Term Potentiation ◽  
Presenilin 2

Background: Mutations in PRESENILIN 2 (PSEN2) cause early onset familial Alzheimer’s disease (EOfAD) but their mode of action remains elusive. One consistent observation for all PRESENILIN gene mutations causing EOfAD is that a transcript is produced with a reading frame terminated by the normal stop codon—the “reading frame preservation rule”. Mutations that do not obey this rule do not cause the disease. The reasons for this are debated. Objective: To predict cellular functions affected by heterozygosity for a frameshift, or a reading frame-preserving mutation in zebrafish psen2 using bioinformatic techniques. Methods: A frameshift mutation (psen2N140fs) and a reading frame-preserving (in-frame) mutation (psen2T141 _ L142delinsMISLISV) were previously isolated during genome editing directed at the N140 codon of zebrafish psen2 (equivalent to N141 of human PSEN2). We mated a pair of fish heterozygous for each mutation to generate a family of siblings including wild type and heterozygous mutant genotypes. Transcriptomes from young adult (6 months) brains of these genotypes were analyzed. Results: The in-frame mutation uniquely caused subtle, but statistically significant, changes to expression of genes involved in oxidative phosphorylation, long-term potentiation and the cell cycle. The frameshift mutation uniquely affected genes involved in Notch and MAPK signaling, extracellular matrix receptor interactions and focal adhesion. Both mutations affected ribosomal protein gene expression but in opposite directions. Conclusion: A frameshift and an in-frame mutation at the same position in zebrafish psen2 cause discrete effects. Changes in oxidative phosphorylation, long-term potentiation and the cell cycle may promote EOfAD pathogenesis in humans.

The effect of research activities and winter precipitation on voiding behaviour of Agassiz’s desert tortoises (Gopherus agassizii)

2014 ◽  
Vol 41 (8) ◽  
pp. 641 ◽  
Author(s):  
Mickey Agha ◽  
Mason O. Murphy ◽  
Jeffrey E. Lovich ◽  
Joshua R. Ennen ◽  
Christian R. Oldham ◽  
...  
Keyword(s):  
Stress Responses ◽  
Handling Time ◽  
Winter Precipitation ◽  
Contact Period ◽  
Gopherus Agassizii ◽  
Desert Tortoise ◽  
Defensive Strategy ◽  
Survivorship Analysis ◽  
Research Activities

Context There is little information available on how research activities might cause stress responses in wildlife, especially responses of threatened species such as the desert tortoise (Gopherus agassizii). Aims The present study aims to detect behavioural effects of researcher handling and winter precipitation on a natural population of desert tortoises in the desert of Southwestern United States, over the period 1997 to 2014, through extensive assessments of capture events during multiple research studies, and capture–mark–recapture survivorship analysis. Methods Juvenile and adult desert tortoises were repeatedly handled with consistent methodology across 18 years during 10 study seasons. Using a generalised linear mixed-effects model, we assessed the effects of both research manipulation and abiotic conditions on probability of voiding. Additionally, we used a Cormack–Jolly–Seber model to assess the effects of winter precipitation and voiding on long-term apparent survivorship. Key results Of 1008 total capture events, voiding was recorded on 83 (8.2%) occasions in 42 different individuals. Our top models indicated that increases in handling time led to significantly higher probabilities of voiding for juveniles, females and males. Similarly, increases in precipitation resulted in significantly higher probabilities of voiding for juveniles and females, but not for males. Tortoise capture frequency was negatively correlated with voiding occurrence. Cormack–Jolly–Seber models demonstrated a weak effect of winter precipitation on survivorship, but a negligible effect for both voiding behaviour and sex. Conclusions Handling-induced voiding by desert tortoises may occur during common research activities and years of above average winter precipitation. Increased likelihood of voiding in individuals with relatively low numbers of recaptures suggested that tortoises may have perceived researchers initially as predators, and therefore voided as a defensive strategy. Voiding does not appear to impact long-term survivorship in desert tortoises at this site. Implications This study has demonstrated that common handling practices on desert tortoise may cause voiding behaviour. These results suggest that in order to minimise undesirable behavioural responses in studied desert tortoise populations, defined procedures or protocols must be followed by the investigators to reduce contact period to the extent feasible.

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