Early Transcriptomic Response to OxLDL in Human Retinal Pigment Epithelial Cells

In the sub-retinal pigment epithelium (sub-RPE) space of the aging macula, deposits of oxidized phospholipids, oxidized derivatives of cholesterol and associated oxidized low-density lipoproteins (OxLDL) are considered contributors to the onset and development of age-related macular degeneration (AMD). We investigated the gene expression response of a human-derived RPE cell line exposed for short periods of time to non-cytotoxic levels of OxLDL or LDL. In our cell model, treatment with OxLDL, but not LDL, generated an early gene expression response which affected more than 400 genes. Gene pathway analysis unveiled gene networks involved in the regulation of various cellular functions, including acute response to oxidative stress via up-regulation of antioxidative gene transcripts controlled by nuclear factor erythroid-2 related factor 2 (NRF2), and up-regulation of aryl hydrocarbon receptor-controlled detoxifying gene transcripts. In contrast, circadian rhythm-controlling genes and genes involved in lipid metabolism were strongly down-regulated. Treatment with low-density lipoprotein (LDL) did not induce the regulation of these pathways. These findings show that RPE cells are able to selectively respond to the oxidized forms of LDL via the up-regulation of gene pathways involved in molecular mechanisms that minimize cellular oxidative damage, and the down-regulation of the expression of genes that regulate the intracellular levels of lipids and lipid derivatives. The effect on genes that control the cellular circadian rhythm suggests that OxLDL might also disrupt the circadian clock-dependent phagocytic activity of the RPE. The data reveal a complex cellular response to a highly heterogeneous oxidative stress-causing agent such as OxLDL commonly present in drusen formations.

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Comparative Gene Expression Analysis Reveals Mechanism of Pinus contorta Response to the Fungal Pathogen Dothistroma septosporum

Molecular Plant-Microbe Interactions ◽

10.1094/mpmi-10-20-0282-r ◽

2020 ◽

Author(s):

Mengmeng Lu ◽

Nicolas Feau ◽

Dragana Obreht Vidakovic ◽

Nicholas Ukrainetz ◽

Barbara Wong ◽

...

Keyword(s):

Gene Expression ◽

Fungal Pathogen ◽

Pinus Contorta ◽

Lodgepole Pine ◽

Selective Constraint ◽

Transcriptomic Response ◽

Gene Expression Response ◽

Gene Modules ◽

Expression Response ◽

Dothistroma Septosporum

Many conifers have distributions that span wide ranges in both biotic and abiotic conditions, but the basis of response to biotic stress has received much less attention than response to abiotic stress. In this study, we investigated the gene expression response of lodgepole pine (Pinus contorta) to attack by the fungal pathogen Dothistroma septosporum, which causes Dothistroma needle blight (DNB), a disease that has caused severe climate-related outbreaks in northwestern British Columbia. We inoculated tolerant and susceptible pines with two D. septosporum isolates and analyzed the differentially expressed genes, differential exon usage, and co-expressed gene modules using RNA-seq data. We found a rapid and strong transcriptomic response in tolerant lodgepole pine samples inoculated with one D. septosporum isolate, and a late and weak response in susceptible samples inoculated with another isolate. We mapped 43 of the DEG- or gene-module-identified genes to the reference plant-pathogen interaction pathway deposited in KEGG database. These genes are present in PAMP-triggered and effector-triggered immunity pathways. Genes comprising pathways and gene modules had signatures of strong selective constraint, while the highly expressed genes in tolerant samples appear to have been favored by selection to counterattack the pathogen. We identified candidate resistance genes that may respond to D. septosporum effectors. Taken together, our results show that gene expression response to D. septosporum infection in lodgepole pine varies both among tree genotypes and pathogen strains, and involves both known candidate genes and a number of genes with previously unknown functions.

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Early gene expression response of barley root tip to toxic concentrations of cadmium

Plant Molecular Biology ◽

10.1007/s11103-021-01233-w ◽

2021 ◽

Author(s):

Ľubica Liptáková ◽

Loriana Demecsová ◽

Katarína Valentovičová ◽

Veronika Zelinová ◽

Ladislav Tamás

Keyword(s):

Gene Expression ◽

Barley Root ◽

Early Gene ◽

Root Tip ◽

Gene Expression Response ◽

Early Gene Expression ◽

Expression Response ◽

Toxic Concentrations ◽

Barley Root Tip

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Evolution Shapes the Gene Expression Response to Oxidative Stress

International Journal of Molecular Sciences ◽

10.3390/ijms20123040 ◽

2019 ◽

Vol 20 (12) ◽

pp. 3040 ◽

Cited By ~ 13

Author(s):

Rima Siauciunaite ◽

Nicholas S. Foulkes ◽

Viola Calabrò ◽

Daniela Vallone

Keyword(s):

Oxidative Stress ◽

Gene Expression ◽

Molecular Mechanisms ◽

Survival Strategies ◽

Cell Physiology ◽

Gene Expression Response ◽

Low Levels ◽

Expression Response ◽

Species Specific ◽

And Function

Reactive oxygen species (ROS) play a key role in cell physiology and function. ROS represents a potential source of damage for many macromolecules including DNA. It is thought that daily changes in oxidative stress levels were an important early factor driving evolution of the circadian clock which enables organisms to predict changes in ROS levels before they actually occur and thereby optimally coordinate survival strategies. It is clear that ROS, at relatively low levels, can serve as an important signaling molecule and also serves as a key regulator of gene expression. Therefore, the mechanisms that have evolved to survive or harness these effects of ROS are ancient evolutionary adaptations that are tightly interconnected with most aspects of cellular physiology. Our understanding of these mechanisms has been mainly based on studies using a relatively small group of genetic models. However, we know comparatively little about how these mechanisms are conserved or have adapted during evolution under different environmental conditions. In this review, we describe recent work that has revealed significant species-specific differences in the gene expression response to ROS by exploring diverse organisms. This evidence supports the notion that during evolution, rather than being highly conserved, there is inherent plasticity in the molecular mechanisms responding to oxidative stress.

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Sulforaphane Enhances the Ability of Human Retinal Pigment Epithelial Cell against Oxidative Stress, and Its Effect on Gene Expression Profile Evaluated by Microarray Analysis

Oxidative Medicine and Cellular Longevity ◽

10.1155/2013/413024 ◽

2013 ◽

Vol 2013 ◽

pp. 1-13 ◽

Cited By ~ 10

Author(s):

Liang Ye ◽

Ting Yu ◽

Yanqun Li ◽

Bingni Chen ◽

Jinshun Zhang ◽

...

Keyword(s):

Oxidative Stress ◽

Gene Expression ◽

Microarray Analysis ◽

Retinal Pigment Epithelial ◽

Nuclear Translocation ◽

Retinal Pigment ◽

Regulation Of Gene Expression ◽

Age Related Macular Degeneration ◽

Rpe Cells ◽

Pigment Epithelial

To gain further insights into the molecular basis of Sulforaphane (SF) mediated retinal pigment epithelial (RPE) 19 cell against oxidative stress, we investigated the effects of SF on the regulation of gene expression on a global scale and tested whether SF can endow RPE cells with the ability to resist apoptosis. The data revealed that after exposure to H2O2, RPE 19 cell viability was increased in the cells pretreated with SF compared to the cell not treated with SF. Microarray analysis revealed significant changes in the expression of 69 genes in RPE 19 cells after 6 hours of SF treatment. Based on the functional relevance, eight of the SF-responsive genes, that belong to antioxidant redox system, and inflammatory responsive factors were validated. The up-regulating translation of thioredoxin-1 (Trx1) and the nuclear translocation of Nuclear factor-like2 (Nrf2) were demonstrated by immunoblot analysis in SF treated RPE cells. Our data indicate that SF increases the ability of RPE 19 cell against oxidative stress through up-regulating antioxidative enzymes and down-regulating inflammatory mediators and chemokines. The results suggest that the antioxidant, SF, may be a valuable supplement for preventing and retarding the development of Age Related Macular Degeneration.

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Gene expression response of mouse lung, liver and white adipose tissue to β-carotene supplementation, knockout of Bcmo1 and sex

Molecular Nutrition & Food Research ◽

10.1002/mnfr.201100194 ◽

2011 ◽

Vol 55 (10) ◽

pp. 1466-1474 ◽

Cited By ~ 9

Author(s):

Yvonne G. J. van Helden ◽

Roger W. L. Godschalk ◽

Johannes von Lintig ◽

Georg Lietz ◽

Jean-Francois Landrier ◽

...

Keyword(s):

Gene Expression ◽

Adipose Tissue ◽

White Adipose Tissue ◽

Mouse Lung ◽

Gene Expression Response ◽

Expression Response ◽

Β Carotene

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Gene expression response of the alga Fucus virsoides (Fucales, Ochrophyta) to glyphosate solution exposure

Environmental Pollution ◽

10.1016/j.envpol.2020.115483 ◽

2020 ◽

Vol 267 ◽

pp. 115483

Author(s):

Marco Gerdol ◽

Andrea Visintin ◽

Sara Kaleb ◽

Francesca Spazzali ◽

Alberto Pallavicini ◽

...

Keyword(s):

Gene Expression ◽

Gene Expression Response ◽

Expression Response

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VExD: A curated resource for human gene expression following viral infection

10.1101/2021.12.02.470974 ◽

2021 ◽

Author(s):

Phillip J Dexheimer ◽

Mario Pujato ◽

Krishna Roskin ◽

Matthew T Weirauch

Keyword(s):

Gene Expression ◽

Viral Infection ◽

Human Gene ◽

Application Programming Interface ◽

Gene Expression Response ◽

Human Gene Expression ◽

Link Type ◽

Uniform Manner ◽

Expression Response ◽

Virus Expression

AbstractMotivationHuman viruses cause significant mortality, morbidity, and economic disruption worldwide. The human gene expression response to viral infection can yield important insights into the detrimental effects to the host. To date, hundreds of studies have performed genome-scale profiling of the effect of viral infection on human gene expression. However, no resource exists that aggregates human expression results across multiple studies, viruses, and tissue types.ResultsWe developed the Virus Expression Database (VExD), a comprehensive curated resource of transcriptomic studies of viral infection in human cells. We have processed all studies within VExD in a uniform manner, allowing users to easily compare human gene expression changes across conditions.Availability and ImplementationVExD is freely accessible at https://vexd.cchmc.org for all modern web browsers. An Application Programming Interface (API) for VExD is also available. The source code is available at https://github.com/pdexheimer/[email protected], [email protected]

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Disruption of TFIIH activities generates a stress gene expression response and reveals possible new targets against cancer

10.1101/862508 ◽

2019 ◽

Author(s):

Maritere Urioistegui-Arcos ◽

Rodrigo Aguayo-Ortiz ◽

María del Pilar Valencia-Morales ◽

Erika Melchy-Pérez ◽

Yvonne Rosenstein ◽

...

Keyword(s):

Gene Expression ◽

Tumour Growth ◽

Transformed Cells ◽

Rna Seq ◽

Gene Expression Response ◽

New Targets ◽

Increased Sensitivity ◽

Promoter Occupancy ◽

Expression Response ◽

Stress Gene

AbstractDisruption of the enzymatic activities of the transcription factor TFIIH by Triptolide (TPL) or THZ1 could be used against cancer. Here, we used an oncogenesis model to compare the effect of TFIIH inhibitors between transformed cells and their progenitors. We report that tumour cells exhibited highly increased sensitivity to TPL or THZ1 and that the combination of both had an additive effect. TPL affects the interaction between XPB and P52, causing a reduction in the levels of XPB, P52, and P8, but not other TFIIH subunits. RNA-Seq and RNAPII-ChIP-Seq experiments showed that although the levels of many transcripts were reduced, the levels of a significant number were increased after TPL treatment, with maintained or increased RNAPII promoter occupancy. A significant number of these genes encode for factors that have been related to tumour growth and metastasis. Some of these genes were also overexpressed in response to THZ1, which depletion enhances the toxicity of TPL and are possible new targets against cancer.

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