Oxidative stress-mediated alterations in histone post-translational modifications

García-Giménez, José-Luis; Garcés, Concepción; Romá‐Mateo, Carlos; Pallardó, Federico V.

doi:10.1016/j.freeradbiomed.2021.02.027

Cited by 36 publications

(28 citation statements)

References 144 publications

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“…The results derived from lens epithelial (21EM15) cells and lenses from KO mice do not support a mechanistic role of NF-κB activation in our experimental settings. Other mechanisms by which oxidative stress can induce cytokine expression include altered histone code [62][63][64][65][66], damaged mitochondrial DNA [67,68], upregulated IRF1 expression [69] and activated AP-1 [66,70], STAT3 [71], NLRP3 [72,73] and MAPK [32] signaling pathways. Which of these mechanisms mediates the effects in the KO lens remains to be established.…”

Section: Discussionmentioning

confidence: 99%

Oxidative stress induces inflammation of lens cells and triggers immune surveillance of ocular tissues

Thompson

Davidson

Chen

et al. 2021

Preprint

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Recent reports have challenged the notion that the lens is immune-privileged. However, these studies have not fully identified the molecular mechanism(s) that promote immune surveillance of the lens. Using a mouse model of targeted glutathione (GSH) deficiency in ocular surface tissues, we have investigated the role of oxidative stress in upregulating cytokine expression and promoting immune surveillance of the eye. RNA-sequencing of lenses from postnatal day (P) 1-aged Gclcf/f;Le-CreTg/- (KO) and Gclcf/f;Le-Cre-/- control (CON) mice revealed upregulation of many cytokines (e.g., CCL4, GDF15, CSF1) and immune response genes in the lenses of KO mice. The eyes of KO mice had a greater number of cells in the aqueous and vitreous humors at P1, P20 and P50 than age-matched CON and Gclcw/w;Le-CreTg/- (CRE) mice. Histological analyses revealed the presence of innate immune cells (i.e., macrophages, leukocytes) in ocular structures of the KO mice. At P20, the expression of cytokines and ROS content was higher in the lenses of KO mice than in those from age-matched CRE and CON mice, suggesting that oxidative stress may induce cytokine expression. In vitro administration of the oxidant, hydrogen peroxide, and the depletion of GSH (using buthionine sulfoximine (BSO)) in 21EM15 lens epithelial cells induced cytokine expression, an effect that was prevented by co-treatment of the cells with N-acetyl-L-cysteine (NAC), a antioxidant. The in vivo and ex vivo induction of cytokine expression by oxidative stress was associated with the expression of markers of epithelial-to-mesenchymal transition (EMT), α-SMA, in lens cells. Given that EMT of lens epithelial cells causes posterior capsule opacification (PCO), we propose that oxidative stress induces cytokine expression, EMT and the development of PCO in a positive feedback loop. Collectively these data indicate that oxidative stress induces inflammation of lens cells which promotes immune surveillance of ocular structures.

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Section: Discussionmentioning

confidence: 99%

Oxidative stress induces inflammation of lens cells and triggers immune surveillance of ocular tissues

Thompson

Davidson

Chen

et al. 2021

Preprint

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“…The results partially revealed the mechanism of m 6 A-specific deposition in the transcriptome. Free radicals as regulators can regulate histone PTMs in directly and indirectly manners and participate in the epigenetic landscape [221], implying that that oxidative stress may regulate m 6 A methylation by affecting the epigenetic regulations. Overall, the achievements above confirmed the crosslink between m 6 A and oxidative stress; however, its potential mechanism remains unclear and needs further research.…”

Section: Oxidative Stress Regulates Mmentioning

confidence: 99%

Cross-Talk between Oxidative Stress and m6A RNA Methylation in Cancer

Yang

Chen

2021

Oxidative Medicine and Cellular Longevity

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Oxidative stress is a state of imbalance between oxidation and antioxidation. Excessive ROS levels are an important factor in tumor development. Damage stimulation and excessive activation of oncogenes cause elevated ROS production in cancer, accompanied by an increase in the antioxidant capacity to retain redox homeostasis in tumor cells at an increased level. Although moderate concentrations of ROS produced in cancer cells contribute to maintaining cell survival and cancer progression, massive ROS accumulation can exert toxicity, leading to cancer cell death. RNA modification is a posttranscriptional control mechanism that regulates gene expression and RNA metabolism, and m6A RNA methylation is the most common type of RNA modification in eukaryotes. m6A modifications can modulate cellular ROS levels through different mechanisms. It is worth noting that ROS signaling also plays a regulatory role in m6A modifications. In this review, we concluded the effects of m6A modification and oxidative stress on tumor biological functions. In particular, we discuss the interplay between oxidative stress and m6A modifications.

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“…Wang et al [ 112 ] reported that histone H2B acetylation is induced in human embryonic cells exposed in vitro to shear flow, regulating chromatin dynamics. Moreover, several histone PTMs have been altered by oxidative stress [ 82 , 113 ] and thus it is expected that simulated microgravity, which generates oxidative and mechanic stress, can affect histone PTMs. Analysis of histone H3 methylation at promoter regions of selected genes in the neuronal lineage of human mesenchymal stem cells incubated in simulated microgravity displayed a decrease of H3K27me3 [ 114 ].…”

Section: Genomic Alterations In Human Cells Cultured In Simulated Space Conditionsmentioning

confidence: 99%

“…The activity of chromatin remodelers, such as histone acetyltransferase (HAT) p300, is altered by oxidative stress [ 113 ]. Alterations in the expression of histone deacetylase (HDAC) genes under microgravity can have consequences at chromatin level.…”

Section: Genomic Alterations In Human Cells Cultured In Simulated Space Conditionsmentioning

confidence: 99%

Genomic Changes Driven by Radiation-Induced DNA Damage and Microgravity in Human Cells

Beheshti

McDonald

Hada

et al. 2021

IJMS

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The space environment consists of a complex mixture of different types of ionizing radiation and altered gravity that represents a threat to humans during space missions. In particular, individual radiation sensitivity is strictly related to the risk of space radiation carcinogenesis. Therefore, in view of future missions to the Moon and Mars, there is an urgent need to estimate as accurately as possible the individual risk from space exposure to improve the safety of space exploration. In this review, we survey the combined effects from the two main physical components of the space environment, ionizing radiation and microgravity, to alter the genetics and epigenetics of human cells, considering both real and simulated space conditions. Data collected from studies on human cells are discussed for their potential use to estimate individual radiation carcinogenesis risk from space exposure.

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Oxidative stress-mediated alterations in histone post-translational modifications

Cited by 36 publications

References 144 publications

Oxidative stress induces inflammation of lens cells and triggers immune surveillance of ocular tissues

Oxidative stress induces inflammation of lens cells and triggers immune surveillance of ocular tissues

Cross-Talk between Oxidative Stress and m6A RNA Methylation in Cancer

Genomic Changes Driven by Radiation-Induced DNA Damage and Microgravity in Human Cells

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