Redox modulation of chromatin remodeling: impact on histone acetylation and deacetylation, NF-kappaB and pro-inflammatory gene expression. Biochem Pharmacol

Department of Environmental Medicine, Division of Lung Biology and Disease, University of Rochester Medical Center, NY, USA.
Biochemical Pharmacology (Impact Factor: 5.01). 10/2004; 68(6):1255-67. DOI: 10.1016/j.bcp.2004.05.042
Source: PubMed


Reactive oxygen species (ROS), either directly or via the formation of lipid peroxidation products, such as 4-hydroxy-2-nonenal, acrolein and F2-isoprostanes, may play a role in enhancing inflammation through the activation and phosphorylation of stress kinases (JNK, ERK, p38) and redox-sensitive transcription factors such as NF-kappaB and AP-1. This increases the expression of genes regulating a battery of distinct pro-inflammatory mediators. Acetylation by histone acetyltransferase (HAT) of specific lysine residues on the N-terminal tail of core histones, results in uncoiling of the DNA and increased accessibility to transcription factor binding. In contrast, histone deacetylation by histone deacetylase (HDAC) represses gene transcription by promoting DNA winding thereby limiting access to transcription factors. Oxidative stress activates NF-kappaB resulting in expression of pro-inflammatory mediators through the activation of intrinsic HAT activity on co-activator molecules. In addition, oxidative stress also inhibits HDAC activity and in doing so enhances inflammatory gene expression which leads to a chronic inflammatory response. Oxidative stress can also increase complex formation between the co-activator CBP/p300 and the p65 subunit of NF-kappaB suggesting a further role of oxidative stress in chromatin remodeling. The antioxidant and/or anti-inflammatory effects of thiol molecules (glutathione, N-acetyl-L-cysteine and N-acystelyn), dietary polyphenols (curcumin-diferuloylmethane and resveratrol), the bronchodilator theophylline and glucocorticoids have all been shown to play a role in either controlling NF-kappaB activation or chromatin remodeling through modulation of HDAC activity and subsequently inflammatory gene expression in lung epithelial cells. Thus, oxidative stress regulates both signal transduction and chromatin remodeling which in turn impacts on pro-inflammatory responses in the lungs.

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    • "GSH is part of numerous basic cellular processes, including protein synthesis, DNA synthesis and repair, cell proliferation, and redox signaling (Meister, 1983; Wu et al., 2004; Townsend, 2007). As an antioxidant, GSH scavenges ROS, RNS (reactive nitrogen species), and other free radicals (Rahman et al., 2004; Haddad and Harb, 2005; Rahman et al., 2005). GSH biosynthetic capacity is controlled by multiple factors, including substrate availability (especially cysteine) and the activity of glutamate cysteine ligase (GCL), the rate-limiting enzyme in GSH synthesis (Griffith, 1999; Griffith and Mulcahy, 1999). "
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    ABSTRACT: The purpose of this study was to evaluate the effect of water temperature on the antioxidant (gills, hemolymph and hepatopancreas) and immunological systems (hemolymph) of Litopenaues vannamei reared with no water exchange. A 60-day trial was conducted at different temperatures (15, 21, 27-control and 33 °C), with 3 replicate tanks for each treatment. The immunologic parameters analyzedwere as follows: hyaline and granular hemocyte count, total protein and apoptosis. The enzymatic and lipid peroxidation assays consisted of glutamate cysteine ligase (GCL), reduced glutathione (GSH) and thiobarbituric acid-reactive substances (TBARS). Therewere no significant differences (p > 0.05) in immunological parameters among treatments throughout the experimental period. Shrimp exposed to 15 °C at 30 days exhibited significantly higher GCL activity in gills compared to 21 °C (1166.28%), 27 °C (422.96%) and 33 °C (809.37%). L. vannamei reared at 15 °C had the highest GSH concentration at 30 days. The GSH increase in gills was 390.29, 376.94 and 361.75% at 21, 27 and 33 °C, respectively. On day 30, shrimp subjected to 33 °C had higher TBARS levels (6157.14; 8620.00 and 14,336.66% at 15, 21 and 27 °C, respectively). Shrimp reared at 15 °C exhibited higher activity of the rate-limiting compound for GSH production (GCL) and higher concentrations of this non-enzymatic antioxidant. This increased activitymay counteract the overproduction of reactive oxygen species generated by temperature stress.We further noted that at 33 °C, the animals showed higher lipid peroxidation. The lowest stress response was observed in shrimp reared at 27 °C (the control group). Therefore, the extreme temperatures should be avoided. Statement/relevance: This study present new results about handling and welfare.
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    • "This epigenetic modification in the chromatin structure is catalyzed by histone deacetylases (HDACs) and histone acetyltransferases (HATs), which are crucial molecular events in regulating gene expression. There is increasing evidences that histone acetylation by HATs and deacetylation by HDACs are in part responsible for regulating pro-inflammatory gene expression, which can be affected by oxidative stress and redox signaling [28] [29]. Oxidative stress can activate p300HAT and result in an enhanced level of histone acetylation that regulates gene expression [30] [31] [32]. "
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    ABSTRACT: Oxidative stress mediated by photodynamic therapy (PDT) mediates the tumoricidal effect, but has also been shown to induce the expression of pro-survival molecules, such as cyclooxygenase-2 (COX-2), which is involved in tumor recurrences after PDT. However, the molecular mechanism is still not fully understood. In this study, we found that activated p38MAPK could significantly up-regulate the activity and expression of histone acetyltransferase p300 (p300HAT) in A375 and C26 cells treated with ALA and chlorin e6 (Ce6) mediated photodynamic treatment. Colony-formation assay showed PDT-induced cytotoxicity was dramatically elevated in the presence of p300HAT inhibitor anacardic acid (AA). Further studies showed that the increased p300HAT acetylates histone H3 and NF-κB p65 subunit to up-regulate the COX-2 expression, which was reduced by AA or p300HAT shRNA. Using chromatin immunoprecipitation analysis, we found that the augmented acetylation of histone H3 and NF-κB increases their binding to the COX-2 promoter region. These in vitro findings were further verified in mice bearing murine C26 and human A375 tumors treated with liposomal Ce6 mediated PDT. Meanwhile, the combination of PDT and AA resulted in a greater tumor regression in BALB/c mice bearing C26 tumors, compared to PDT only or combined with COX-2 inhibitor. Finally, we demonstrated that suppression of the PDT-induced p300HAT activity also resulted in the decreased expression of survivin, restoring caspase-3 activity and sensitizing PDT-treated cells from autophagy to apoptosis due to the Becline-1 cleavage. This study demonstrates for the first time the molecular mechanisms involved in histone modification induced by PDT-mediated oxidative stress, suggesting that HAT inhibitors may provide a novel therapeutic approach for improving PDT response. Copyright © 2015. Published by Elsevier Inc.
    Free Radical Biology and Medicine 05/2015; 86. DOI:10.1016/j.freeradbiomed.2015.05.009 · 5.74 Impact Factor
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    • "In vivo, overexpression of SIRT1 reduces hepatic expression of TNF-a and IL-6 after chronic high-fat feeding [36]. The antioxidant and/or antiinflammatory effects of resveratrol have been demonstrated to play a role in either controlling NF-kB activation or chromatin remodeling through modulation of histone deacetylase (as sirtuins) activity and subsequently inflammatory gene expression in lung epithelial cells [37]. Other studies support the scenario in which immune responses and the aging process can be enforced by the potentiation of NF-kB transactivation efficiency. "
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    ABSTRACT: Objective: Resveratrol (RSV) is the most studied natural compound that activates sirtuins, which produce beneficial metabolic effects on lipid and glucose metabolism. The aim of the present study was to investigate the role of resveratrol in preventing nonalcoholic fatty liver disease (NAFLD) and expression of liver inflammatory markers in mice treated with a high-fat diet. Methods and procedures: Eighteen male mice were divided into three groups and fed for 60 d with a standard diet (ST), high-fat diet (HFD), or high-fat diet plus resveratrol (HFD + RSV, 30 mg/kg/d). Body weight, food intake, and serum total cholesterol, triacylglycerol, insulin, alanine transaminase (ALT), and aspartate aminotransferase (AST) were evaluated. Liver histology was analyzed. Expression of ACC, PPAR-γ, ChREBP, SREBP-1 c, CPT-1, tumor necrosis factor α (TNF-α), interleukin 6 (IL-6), NF-κB, interleukin 1 β (IL-1 β), and SIRT1 were evaluated by quantitative real-time reverse transcriptase PCR (qRT-PCR). Results: The major finding of the present study was that RSV reduced body fat, total cholesterol, triacylglycerol, transaminases, and insulin plasma level. These results were accompanied with a significant reduction in TNF-α, IL-6, and NF-κB mRNA expression in the liver. Analyses of liver adipogenesis related genes indicated that ACC, PPAR-γ, and SREBP-1 mRNA expression were significantly suppressed in HFD + RSV mice. In addition, we observed increased expression of SIRT1 in the HFD + RSV group. Conclusions: We observed that treatment with resveratrol improved lipid metabolism, and decreased NAFLD and pro-inflammatory profile in liver of mice with obesity-inducible diets. These data suggest an important clinical application of RSV in preventing liver diseases.
    Nutrition 07/2014; 30(7-8):915-9. DOI:10.1016/j.nut.2013.11.016 · 2.93 Impact Factor
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