The Transcriptional Response to Oxidative Stress is Independent of Stress-Granule Formation

Cells respond to stress with translational arrest, robust transcriptional changes, and transcription-independent formation of mRNP assemblies termed stress granules (SGs). Despite considerable interest in the role of SGs in oxidative, unfolded-protein and viral stress responses, whether and how SGs contribute to stress-induced transcription has not been rigorously examined. To address this, we characterized transcriptional changes in Drosophila S2 cells induced by acute oxidative-stress and assessed how these were altered under conditions that disrupted SG assembly. Oxidative stress for 3-hours predominantly resulted in induction or upregulation of stress-responsive mRNAs whose levels peaked during recovery after stress cessation. The stress-transcriptome is enriched in mRNAs coding for chaperones, including HSP70s, small heat shock proteins, glutathione transferases, and several non-coding RNAs. Oxidative stress also induced cytoplasmic SGs that disassembled 3-hours after stress cessation. As expected, RNAi-mediated knockdown of the conserved G3BP1/Rasputin protein inhibited SG assembly. However, this disruption had no significant effect on the stress-induced transcriptional response or stress-induced translational arrest. Thus, SG assembly and stress-induced gene expression alterations appear to be driven by distinctive signaling processes. We suggest that while SG assembly represents a fast, transient mechanism, the transcriptional response enables a slower, longer-lasting mechanism for adaptation to and recovery from cell stress.

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THE TRANSCRIPTIONAL RESPONSE TO OXIDATIVE STRESS IS INDEPENDENT OF STRESS-GRANULE FORMATION

10.1101/2021.08.18.456454 ◽

2021 ◽

Author(s):

Amanjot Singh ◽

Arvind Reddy Kandi ◽

Deepa Jayaprakashappa ◽

Guillaume Thuery ◽

Devam J Purohit ◽

...

Keyword(s):

Oxidative Stress ◽

Stress Responses ◽

Transcriptional Response ◽

Stress Granules ◽

Stress Granule ◽

Cell Recovery ◽

Granule Formation ◽

Transcriptional Changes ◽

Translational Arrest ◽

Shock Proteins

ABSTRACTCells respond to stress with translational arrest, robust transcriptional changes, and transcription-independent formation of mRNP assemblies termed stress granules (SGs). Despite considerable interest in the role of SGs in oxidative, unfolded-protein, and viral stress responses, whether and how SGs contribute to stress-induced transcription has not been rigorously examined. To address this issue, we characterized transcriptional changes in Drosophila S2 cells induced by acute oxidative-stress and assessed how these were altered under conditions that disrupted SG assembly. Sodium-arsenite stress for 3 hours predominantly resulted in the induction or upregulation of stress-responsive mRNAs whose levels peaked during cell recovery after stress cessation. The stress-transcriptome is enriched in mRNAs coding for protein chaperones, including HSP70 and low molecular-weight heat shock proteins, glutathione transferases, and several non-coding RNAs. Oxidative stress also induced prominent cytoplasmic stress granules that disassembled 3-hours after stress cessation. As expected, RNAi-mediated knockdown of the conserved G3BP1/ Rasputin protein inhibited stress-granule assembly. However, this disruption had no significant effect on the stress-induced transcriptional response or stress-induced translational arrest. Thus, SG assembly and stress-induced effects on gene expression appear to be driven by distinctive signaling processes. We suggest that while SG assembly represents a fast, transient mechanism, the transcriptional response enables a slower, longer-lasting mechanism for adaptation to and recovery from cell stress.

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The Transcriptional Response to a Peroxisome Proliferator-activated Receptor α Agonist Includes Increased Expression of Proteome Maintenance Genes

Journal of Biological Chemistry ◽

10.1074/jbc.m409347200 ◽

2004 ◽

Vol 279 (50) ◽

pp. 52390-52398 ◽

Cited By ~ 64

Author(s):

Steven P. Anderson ◽

Paul Howroyd ◽

Jie Liu ◽

Xun Qian ◽

Rainer Bahnemann ◽

...

Keyword(s):

Oxidative Stress ◽

Stress Responses ◽

Transcriptional Response ◽

Lipid Homeostasis ◽

Peroxisome Proliferator ◽

Wild Type ◽

Peroxisome Proliferator Activated Receptor ◽

Proteasomal Genes ◽

Oxidative Stress Responses

The nuclear receptor peroxisome proliferator-activated receptor α (PPARα), in addition to regulating lipid homeostasis, controls the level of tissue damage after chemical or physical stress. To determine the role of PPARα in oxidative stress responses, we examined damage after exposure to chemicals that increase oxidative stress in wild-type or PPARα-null mice. Primary hepatocytes from wild-type but not PPARα-null mice pretreated with the PPAR pan-agonist WY-14,643 (WY) were protected from damage to cadmium and paraquat. The livers from intact wild-type but not PPARα-null mice were more resistant to damage after carbon tetrachloride treatment. To determine the molecular basis of the protection by PPARα, we identified by transcript profiling genes whose expression was altered by a 7-day exposure to WY in wild-type and PPARα-null mice. Of the 815 genes regulated by WY in wild-type mice (p≤ 0.001; ≥1.5-fold or ≤-1.5-fold), only two genes were regulated similarly by WY in PPARα-null mice. WY increased expression of stress modifier genes that maintain the health of the proteome, including those that prevent protein aggregation (heat stress-inducible chaperones) and eliminate damaged proteins (proteasome components). Although the induction of proteasomal genes significantly overlapped with those regulated by 1,2-dithiole-3-thione, an activator of oxidant-inducible Nrf2, WY increased expression of proteasomal genes independently of Nrf2. Thus, PPARα controls the vast majority of gene expression changes after exposure to WY in the mouse liver and protects the liver from oxidant-induced damage, possibly through regulation of a distinct set of proteome maintenance genes.

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Causal role of oxidative stress in unfolded protein response development in the hyperthyroid state

Free Radical Biology and Medicine ◽

10.1016/j.freeradbiomed.2015.09.004 ◽

2015 ◽

Vol 89 ◽

pp. 401-408 ◽

Cited By ~ 9

Author(s):

Luis A. Videla ◽

Virginia Fernández ◽

Pamela Cornejo ◽

Romina Vargas ◽

Juan Carrasco ◽

...

Keyword(s):

Oxidative Stress ◽

Unfolded Protein Response ◽

Causal Role ◽

Unfolded Protein ◽

Hyperthyroid State ◽

Protein Response

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Roles of Autophagy in Oxidative Stress

International Journal of Molecular Sciences ◽

10.3390/ijms21093289 ◽

2020 ◽

Vol 21 (9) ◽

pp. 3289 ◽

Cited By ~ 4

Author(s):

Hyeong Rok Yun ◽

Yong Hwa Jo ◽

Jieun Kim ◽

Yoonhwa Shin ◽

Sung Soo Kim ◽

...

Keyword(s):

Oxidative Stress ◽

Cell Death ◽

Stress Responses ◽

Basic Mechanism ◽

Redox Signalling ◽

Mitochondrial Ros ◽

Related Stress ◽

And Function ◽

Catabolic Process

Autophagy is a catabolic process for unnecessary or dysfunctional cytoplasmic contents by lysosomal degradation pathways. Autophagy is implicated in various biological processes such as programmed cell death, stress responses, elimination of damaged organelles and development. The role of autophagy as a crucial mediator has been clarified and expanded in the pathological response to redox signalling. Autophagy is a major sensor of the redox signalling. Reactive oxygen species (ROS) are highly reactive molecules that are generated as by-products of cellular metabolism, principally by mitochondria. Mitochondrial ROS (mROS) are beneficial or detrimental to cells depending on their concentration and location. mROS function as redox messengers in intracellular signalling at physiologically low level, whereas excessive production of mROS causes oxidative damage to cellular constituents and thus incurs cell death. Hence, the balance of autophagy-related stress adaptation and cell death is important to comprehend redox signalling-related pathogenesis. In this review, we attempt to provide an overview the basic mechanism and function of autophagy in the context of response to oxidative stress and redox signalling in pathology.

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Unravelling the cross-talk between iron starvation and oxidative stress responses highlights the key role of PerR (alr0957) in peroxide signalling in the cyanobacteriumNostoc PCC 7120

Environmental Microbiology Reports ◽

10.1111/1758-2229.12157 ◽

2014 ◽

Vol 6 (5) ◽

pp. 468-475 ◽

Cited By ~ 21

Author(s):

Fan Yingping ◽

Sylvain Lemeille ◽

Emmanuel Talla ◽

Annick Janicki ◽

Yann Denis ◽

...

Keyword(s):

Oxidative Stress ◽

Cross Talk ◽

Stress Responses ◽

Iron Starvation ◽

The Cross ◽

Pcc 7120 ◽

Oxidative Stress Responses ◽

And Oxidative Stress

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Role of Calprotectin in Withholding Zinc and Copper from Candida albicans

Infection and Immunity ◽

10.1128/iai.00779-17 ◽

2017 ◽

Vol 86 (2) ◽

Cited By ~ 36

Author(s):

Angelique N. Besold ◽

Benjamin A. Gilston ◽

Jana N. Radin ◽

Christian Ramsoomair ◽

Edward M. Culbertson ◽

...

Keyword(s):

Candida Albicans ◽

Stress Responses ◽

Metal Binding ◽

Content Type ◽

Nutritional Immunity ◽

Numerous Cell ◽

Transcriptional Changes ◽

Opportunistic Fungal Pathogen ◽

First Time

ABSTRACT The opportunistic fungal pathogen Candida albicans acquires essential metals from the host, yet the host can sequester these micronutrients through a process known as nutritional immunity. How the host withholds metals from C. albicans has been poorly understood; here we examine the role of calprotectin (CP), a transition metal binding protein. When CP depletes bioavailable Zn from the extracellular environment, C. albicans strongly upregulates ZRT1 and PRA1 for Zn import and maintains constant intracellular Zn through numerous cell divisions. We show for the first time that CP can also sequester Cu by binding Cu(II) with subpicomolar affinity. CP blocks fungal acquisition of Cu from serum and induces a Cu starvation stress response involving SOD1 and SOD3 superoxide dismutases. These transcriptional changes are mirrored when C. albicans invades kidneys in a mouse model of disseminated candidiasis, although the responses to Cu and Zn limitations are temporally distinct. The Cu response progresses throughout 72 h, while the Zn response is short-lived. Notably, these stress responses were attenuated in CP null mice, but only at initial stages of infection. Thus, Zn and Cu pools are dynamic at the host-pathogen interface and CP acts early in infection to restrict metal nutrients from C. albicans.

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Chemotherapy: induction of stress responses

Endocrine Related Cancer ◽

10.1677/erc.1.01272 ◽

2006 ◽

Vol 13 (Supplement_1) ◽

pp. S115-S124 ◽

Cited By ~ 57

Author(s):

E Tiligada

Keyword(s):

Anticancer Agents ◽

Stress Responses ◽

Chemotherapeutic Agents ◽

Clinical Value ◽

Unfolded Protein ◽

The Unfolded Protein Response ◽

Shock Proteins ◽

And Function ◽

Protein Response ◽

Functional Components

Eukaryotic cells, from yeast to mammals, respond and adapt to environmental and microenvironmental stressors by evolutionary conserved multicomponent endogenous systems that utilise a network of signal transduction pathways to regulate the adaptive and protective phenotype. The balance between cell survival and cell death is decisive for sensitivity or resistance to DNA-damaging chemotherapeutic agents. Anticancer drugs may themselves act as stressors to induce adaptive signals that could limit their clinical value. Related research has been focused on the modulation of the expression and function of the heat shock proteins, the unfolded protein response, the mechanisms of subcellular translocation of signalling components, the genomic and non-genomic actions of drugs and endogenous functional components like hormonal pathways, the input of inflammation and alterations in the microenvironmental milieu and on the control of the cell cycle and proliferation. The outcome seems to be driven by the first-line responses that support cellular integrity and by specific mechanisms that depend on the type of cell and the nature, and duration and severity of the noxious stimulus. Data obtained from experimental organisms like the yeast have added valuable information on the basic conservation in cellular stress-related processes in eukaryotes and on the consequences that may accompany the adaptive and protective phenotype during the stress response to anticancer agents. Understanding the complex molecular pathways mediating these processes has started to contribute to the reevaluation of the current therapeutic regiments and to revolutionise the approaches for improved anticancer therapy.

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The role of oxidative stress in the induction of Drosophila heat-shock proteins

Experimental Cell Research ◽

10.1016/0014-4827(87)90284-9 ◽

1987 ◽

Vol 173 (2) ◽

pp. 439-449 ◽

Cited By ~ 22

Author(s):

Ian A.S. Drummond ◽

Richard A. Steinhardt

Keyword(s):

Oxidative Stress ◽

Heat Shock ◽

Heat Shock Proteins ◽

Shock Proteins

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Role of the Hog1 Stress-activated Protein Kinase in the Global Transcriptional Response to Stress in the Fungal PathogenCandida albicans

Molecular Biology of the Cell ◽

10.1091/mbc.e05-06-0501 ◽

2006 ◽

Vol 17 (2) ◽

pp. 1018-1032 ◽

Cited By ~ 253

Author(s):

Brice Enjalbert ◽

Deborah A. Smith ◽

Michael J. Cornell ◽

Intikhab Alam ◽

Susan Nicholls ◽

...

Keyword(s):

Oxidative Stress ◽

Heavy Metal ◽

Protein Kinase ◽

Transcriptional Response ◽

Heavy Metal Stress ◽

Transcriptional Responses ◽

Stress Genes ◽

The Core ◽

Response To Stress

The resistance of Candida albicans to many stresses is dependent on the stress-activated protein kinase (SAPK) Hog1. Hence we have explored the role of Hog1 in the regulation of transcriptional responses to stress. DNA microarrays were used to characterize the global transcriptional responses of HOG1 and hog1 cells to three stress conditions that activate the Hog1 SAPK: osmotic stress, oxidative stress, and heavy metal stress. This revealed both stress-specific transcriptional responses and a core transcriptional response to stress in C. albicans. The core transcriptional response was characterized by a subset of genes that responded in a stereotypical manner to all of the stresses analyzed. Inactivation of HOG1 significantly attenuated transcriptional responses to osmotic and heavy metal stresses, but not to oxidative stress, and this was reflected in the role of Hog1 in the regulation of C. albicans core stress genes. Instead, the Cap1 transcription factor plays a key role in the oxidative stress regulation of C. albicans core stress genes. Our data show that the SAPK network in C. albicans has diverged from corresponding networks in model yeasts and that the C. albicans SAPK pathway functions in parallel with other pathways to regulate the core transcriptional response to stress.

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